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Additional Spread of Tamiflu Resistant Pandemic H1N1
Recombinomics Commentary 20:07
August 12, 2009

Charles Penn, a scientist with the Geneva-based agency, says the WHO has also been alerted informally to the discovery of a small number of other Tamiflu-resistant viruses but he won't say where they were found.

The above comments describe additional cases of Tamiflu resistance (H274Y) but provide no detail on the circumstances or locations.  Who has acknowledged the resistance that was evident in the sequences released from Singapore and Hunan, China, as well as the examples previously described in Denmark, Canada, Hong Kong, and Japan (3 times).  However, the number and location of additional cases and circumstances remains unclear.

Media reports have described H274Y in Thailand, but it remains unclear how many cases were found.  In addition, there were reports of resistance along the Texas / Mexican border, but those reports were denied.  However, the denial only addressed the cited locations.  There was no statement that the rumored cases were false. The media report was quite detailed about the cases (at least two), which raised concerns that the resistance was widespread, because multiple cases were reported in the same general area.

To date there are no reports of resistance developing during treatment. Several cases were discovered in patients receive prophylactic Tamiflu, but the development of symptoms on the fifth day or prophylactic treatment suggested the H274Y discovered was already present as a minor component and the preventive treatment led to the discovery of the H274Y.

All reported cases have H274Y, which matches the change in seasonal H1N1 and each pandemic sequence represents a different genetic background, raising concerns that the H274Y is spreading via recombination in mild cases which are not tested and in cases were the virus is a mixture dominated by wild type. Consequently, new isolates are being discovered, although reports are clearly being delayed.

The Singapore sequence, deposited at GISAID last week was from the third patient confirmed in Singapore, an American (28F) who became ill in flight from Honolulu to Singapore. Her cases was mild and she was discharged on May 31, three days after confirmation.  Similarly, the sequence from Hunan was also released last week, from a patient (63F) which was confirmed June 13. These long delays, and the WHO refusal to give detail on the additional cases, increase concerns that the H274Y is widespread and it presence is either not being detected, or not being reported.

Details on the number and locations of the other isolates, as well as the circumstance surrounding the detection, would be useful.  The patient from Hong Kong was not linked to Tamiflu, and circumstances surrounding cases in Singapore, China, and Thailand suggest that the H274Y was discovered during routine surveillance and therefore collected in the absence of or prior to oseltamivir treatment, raising additional concerns of spread of evolutionarily fit pandemic H1N1 with H274Y.

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