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H1N1 Tamiflu Resistance Linked to Brisbane Strain

Recombinomics Commentary 22:17
April 20, 2008

A total of 200 (69%) of 290 influenza A (H1N1) viruses were characterized as A/Solomon Islands/3/2006-like, the influenza A (H1N1) component of the 2007--08 influenza vaccine for the Northern Hemisphere, and 70 (24%) were characterized as A/Brisbane/59/2007-like, the recommended H1N1 component of the 2008--09 Northern Hemisphere vaccine.

All the oseltamivir-resistant viruses have been influenza A (H1N1) viruses and have been determined to share the same genetic mutation that confers oseltamivir resistance. These 84 viruses represent 10.2% of the 824 influenza A (H1N1) viruses that have been tested, an increase from four (0.7%) of 588 influenza A (H1N1) viruses tested during the 2006--07 season.

The above comments are from the recent MMWR on the influenza season in the United States.  Recently, sequences from the current flu season have been released at Genbank, and sixteen had H274Y.  However, all were A/Brisbane/59/2007-like suggesting that the frequency of H274Y in the Brisbane strain may be significantly higher than the 10.2% found in H1N1 in the US.  Since Brisbane only represents 24% of the H1N1 isolates in the US, if H274Y is concentrated in Brisbane, the frequency of H274Y in the Brisbane strain could be closer to 40%.  Indeed, there have been 56 NA Brisbane sequences released, so the 16 with H274Y represent 29% of the Brisbane/59 isolates in the US.

The frequency of Brisbane/59 in European countries may also explain the differences in H274Y frequencies.  In the recent WHO report on next year’s vaccine targets, two isolates with H274Y were mentioned, A/Paris/577/2007 and A/Norway/1735/2007, and both were the Brisbane strain.  Norway and France have the highest levels of reported H274Y.

Similarly, two H274Y sequences were released at Genbank this week from Turkey and England, and both were identical to Brisbane-like sequences in the US.

Thus, all public H1N1 sequences from the current season with H274Y have been the Brisbane strain, suggesting that the differences in H274Y frequencies in Europe are largely linked to the frequency of of the Brisbane strain in those countries.

The WHO recommendation, as well as the CDC recommendation, includes Brisbane/59 as the H1N1 target for the fall trivalent vaccine, indicating that Brisbane is becoming dominant and the frequencies of H274Y in H1N1 will increase.  Moreover, the current vaccine, which is directed against Solomon Island-like H1N1 may have contributed to the increase in the H274Y frequency by limiting Solomon Island infections.

More information on the association of H274Y with the Brisbane strain would be useful.

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