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Emergence of H1N1pdm09 Tamiflu Resistance in North America
Recombinomics Commentary 19:30
May 19, 2012

Thirteen had no exposure to oseltamivir; out of those 13 patients, 2 had family members using oseltamivir.

Eleven of the 16 oseltamivir-resistant viruses were collected from January to April 2012 and are from Texas

Although clonal expansion of H274Y Tamiflu resistance in H1N1pdm09 has been noted in Japan and Australia, the expansion described in the week 19 FluView (noted above) represents the most serious expansion to date.

H1N1pdm09 in the 2011/2012 season in Mexico has been the dominant influenza in circulation.  The activity, coupled with deaths, has led to increased surveillance in Mexico and adjacent areas in the United States.  Sequence of isolates from late 2011 and early 2012 collections were closely related to sequences from Texas.

In February Biologia Molecular y Validacion de Tecnicas in Santo Tomas, Mexico released (at Genbank) two sets of H1N1pdm09 sequences (A/Mexico/InDRE689/2012 and A/Mexico/InDRE1474/2012) from two Mexico City cases (35F, 2M) collected on January 19 and 26, 2012, respectively.  Both NA sequences had H274Y and the sequences were closely related to the earlier sequences from Mexico and Texas.
The US CDC subsequently released 4 sets of sequences from Mexico, including collections from the two cases above, (A/Mexico/689/2012, A/Mexico/1474/2012, A/Mexico/1818/2012, A/Mexico/2440/2012) and all four had H274Y.  In addition five NA sequences from Texas were released (A/Texas/23/2012, A/Texas/24/2012, A/Texas/26/2012, A/Texas/29/2012, A/Texas/30/2012), which also had H274Y.  The Texas sequences were collected over a longer time frame (January-March) and all sequences were closely related signaling clonal expansion. 

The CDC subsequently released four additional NA sequences from March collections (A/Texas/31/2012, A/Texas/33/2012, A/Texas/34/2012, A/Texas/35/2012) as well as sequences outside of Texas (A/California/21/2012) and A/Illinois/1/2012), which also had H274Y and were also closely related to the above isolates from Texas and Mexico).

The nine sets of sequences from Texas represent most of the 11 cases described by the CDC (the two missing sequences are likely from April), while the two US non-Texas sequences are among the five cited above (the missing three may also represent April collections – the most recent CDC sequences are from March).

The CDC description in week 19 FluView support clonal expansion since 13/16 cases had no Tamiflu exposure.  Moreover, at least one of the three with Tamiflu exposure had reportable H274Y after 1 day of treatment, indicating H274Y was present prior to treatment.  H274Y in two family members further support transmission of Tamiflu resistant H1N1pdm09, and at least two of the cases outside of Texas also had no exposure to Tamiflu.

The extended timeframe (January through April) and the wide geographical reach (Mexico City to Texas followed by spread to California and Illinois) indicate H274Y is far more widespread than the 22 confirmed cases in the United States and Mexico.  Moreover, the spread is in a subclade that is dominant in Mexco and Texas, but has also spread throughout the United States.

Although the current flu season in the United States and Mexico is ending, the spread of this sub-clade to the southern hemisphere is likely, raising concerns that the spread to H274Y in H1N1pdm09 will mimic the fixing of H274Y in seasonal H1N1 in the 2008/2009 flu season.

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