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Tamiflu Resistant Pandemic H1N1 in Thailand
Recombinomics Commentary 00:25
August 9, 2009

Health experts are urging the public to stay calm after the first case of a Thai H1N1 flu patient developing resistance to the main drug prescribed to treat the virus was found.

The discovery of a H1N1 strain which is resistant to the antiviral drug oseltamivir was made in laboratory tests at Ramathibodi Hospital.

The above description describes the first reported case of oseltamivir (Tamiflu) in a pandemic H1N1 patient in Thailand.  The report follows the relase of a sequence from Hunan, China with H274Y, which followed the release of a sequence from a patient in Singapore, which followed the release of the sequence with H274Y from a patient in Demark.  All three sequences were distinct from each other, as well as previous sequences from Japan (Osaka and Yamaguchi) and Hong Kong.  Moreover, H274Y has been reported in sequences from patients in Quebec and Tokushima.

The recent release of the sequences signals global spread of resistance, but the report from Thailand creates additional concerns.  The number of lab confirmed cases in Thailand should now be above 10,000 and the number of lab confirmed fatalities likely tops 100 (see details in map links), The confirmed cases and deaths have been on a sharp upward slope and the contribution of the resistance to the large number of deaths is unclear.

Similarly, the report does not indicate the treatment status of the patient, who recovered.  Previously, most of the described patients were identified while on prophylactic Tamiflu.  Thus, development of symptoms while on Tamiflu led to the isolate and sequencing or the reported isolates.  However, the resistance in the Thai patient was identified during routine screening raising concerns that the patient was not treated with Tamifu. 

The prior isolate from Hong Kong was from a patient traveling from San Francisco who had a mild case and did not receive Tamiflu, before or after she tested positive.  Similarly, the sequences from Singapore and Hunan were quietly released at GISAID or Genbank, raising concerns that the resistance was identified during routine sequencing, since the samples were collected in May and mid June, but not reported until this week.

These latest results signal global spread of Tamiflu resistance, which may be associated with evolutionarily fit pandemic H1N1.

Details on the circumstances associated with the resistant patients in Singapore, Hunan, China, and Thailand would be useful.

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