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Widespread H1N1 Tamiflu Resistance in Canada
Recombinomics Commentary 19:33
January 4, 2009

all of the A/H1N1 isolates were resistant to oseltamivir due to the H274Y mutation (resistance = 100% or 5/5). The resistant isolates were from NS, ON and BC.

To date this season, 19 influenza isolates in BC have been sub-typed as A/H1 and were assessed genotypically for oseltamivir resistance using an SNP assay. Fourteen isolates tested positive for the H274Y mutation (resistance = 100% or 14/14), with the other 5 specimens still pending confirmatory testing. These specimens were from community-based cases of ILI

The above comments from the week 51 report from Canada confirm H1N1 Tamiflu resistance is at 100% in Canada and widespread.  Although most of the testing has been in British Columbia, where 83% of reported influenza is H1N1, samples from Ontario and Nova Scotia have also been tested and all have H274Y.

The results in Canada parallel those in the United States where 64 of 65 H1N1 isolates had H274Y.  The sole sensitive sample was clade 2C isolated in California on September 4, 2008 as indicated in the sequence, A/California/07/2008, released by the CDC.  The other released sequences, from Hawaii, Texas, Pennsylvania, and Wisconsin were clade 2B and had H274Y.  Thus, like Canada, all clade 2B isolates have had H274Y and the resistance is also widespread in the United States, where more than 90% of influenza A isolates were H1N1.

Similar frequencies in H1N1 were also seen in Europe, where most reported data is from the UK.  However, all H1N1 isolates from Scotland, Wales, Norway, and Sweden also had H274Y, although most reported influenza A in Europe has been H3N2.

The high frequency of H1N1 in the United States had led to a CDC advisory on oseltamivir usage in the United States

Since the H274Y was acquired by homologous recombination, the large reservoir of H274Y in H1N1 seasonal flu has serious implications for the utility of oseltamivir in the control of H5N1 pandemic influenza, which can acquire H274Y in patients co-infected with H5N1 and H1N1.

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