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Emerging H5N1Tamiflu Resistance in Northern Vietnam

Recombinomics Commentary
May 18, 2005
>> Sequence analysis of NA genes and neuraminidase inhibitor susceptibility testing of H5N1 human 2005 isolates from Viet Nam has also revealed that one virus (A/VN/HN30408/05) has a "mixed" virus population of amino acid residues 274-H (wild-type) and 274-Y (resistant) sequences. Although this virus does not exhibit a fully resistant phenotype, the IC50 value for oseltamivir is shifted upward and consequently this virus is less susceptible to oseltamivir than other H5N1 isolates tested. The patient from whom this virus was isolated had been/was being treated with oseltamivir. The community emergence and spread of viruses resistant to oseltamivir, if it were to occur, would have significant implications for influenza A/H5N1 prevention and control.  <<

The emergence of H5N1 Tamiflu-resistance is cause for concern.  This "mixed" infection is common and such dual infections generate recombinants.  Most of the prior dual infections were in animals.  This mixed infection in a recovering patient is cause for concern.  Treatment of the patient with Tamiflu will likely select for H274Y.  In the hospital setting, this emerging virus will probably not transmit beyond the patient being treated.

However, the cases in northern Vietnam are milder, and treatment of milder cases with Tamiflu may select H274Y, which could then be transmitted.  Tamiflu resistance in the small number of confirmed H5N1 cases suggest that H5N1 resistant strains will emerge rapidly, ending hopes of bird flu containment with Tamiflu.

Moreover, since the 2005 H5N1 isolates are more heterogeneous and the isolates in northern Vietnam are distinct from isolates in southern Vietnam, which have a high associated case fatality rate, further recombinants with increase virulence and Tamiflu resistance combined with improved human-to-human transmission are possible.

H5N1 has become endemic to birds in Vietnam and Thailand.  The distribution of H5N1 in people is largely unknown.  These combinations and potential interactions complicate H5N1 control efforts.

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