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Independent Acquistions of Tamiflu Resistance in the US

Recombinomics Commentary 13:11
March 22, 2008

The US Center for Disease Control (CDC) has released addition H1N1 sequences, including those from 2008 isolates.  These data include additional NA sequences with H274Y (see list here).  The new data supports multiple introductions of H274Y, which creates significant problems for current influenza genetics dogma, which maintains that such changes are due to selection of random mutations.

The problem of Tamiflu resistance has become increasingly clear.  It achieved widespread notice when countries in Europe began reporting the resistance.  All of the resistance was in H1N1 seasonal flu, but the sudden appearance was not linked to Tamiflu usage.  The highest frequency was initially reported in Norway, and the high frequency has been maintained.  In the latest report, 127 of 184 H1N1 isolates (69%) are H274Y positive.  Similarly, 106 of 279 H1N1 isolates (38%) in France have H274Y.  In contrast, in countries such as Japan, which have higher frequencies of Tamiflu usage, the frequency is only 5%.  In the United States, the frequency in the latest CDC weekly report is 9.1% (59 of 646 H1N1 isolates).

In the United States, the earlier resistance (2006/2007 season) was exclusively in the New Caledonia strain.  This season, all of the recently released positives are in the Brisbane/59 strain.  However, these new isolates represent two independent acquisitions.  One branch of the phylogenetic tree is composed of isolates from Hawaii and California,  Two of the isolates on this branch have H274Y and both are from Hawaii.  These data represent a recent acquisition because H274Y is only in a subset of the isolates.  A separate branch is more widespread in the US.  The two states with the most positives on this branch are Arizona and New Jersey (see list below).

The presence of H274Y on multiple branches of phylogenetic trees of H1N1 isolates raises serious questions about current dogma on influenza genetics.  Continued selection of H274Y is not consistent with Tamiflu usage or the branch clustering, which is highlighted by the phylogenetic analysis and the sudden appearance of the resistance in the US or other countries, especially Norway and France where the frequency of H274Y is alarmingly high.

New Caledonia-like sequences


Brisbane/59-like sequences

Mainland branch



New Jersey/06/2007
New Jersey/15/2007
New Jersey/16/2007
New Jersey/20/2007
New Jersey/05/2008

"Western" branch

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