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Tamiflu Resistant H5N1 in Vietnam?
Recombinomics Commentary
May 17, 2005
>> The genetic changes they have seen in the northern Vietnam viruses are in the gene that codes for the spike, a molecule called haemaglutinin, in a part that controls how well the spike fits into the receptor…….
One final surprise too. One recent sample from Vietnam proved to be, in part, resistant to the drug mainly used to treat victims of H5N1.
Chances are it's a one-off - the patient was being treated with the drug - but the WHO scientists warn that if further samples are found, it would have serious implications indeed. <<
The above comments on changes in HA suggest that the protein that is missing one amino acid is HA, and the missing amino acid is in the poly-basic cleavage site. If so, it is likely that the missing amino acid matches the missing amino acid in H5N1 found in Shanghai and other provinces in eastern China. These data suggest that the new H5N1 in northern Vietnam is indeed a recombinant between the H5N1 in Vietnam and the H5N1 in China.
The data also suggests that H5N1 in China is being under-reported, adding to the misinformation provided by the poor surveillance of H5N1. China, like all Asian countries that had H5N1 last year or this year, has not submitted any publicly available 2005 H5N1 sequences to GenBank. The sequences held by WHO consultants, but not shared with the rest of the scientific community, may indeed provide clues that WHO appears to have trouble interpreting beyond a funny noise in a car.
Thus, media reports suggest that significant changes are occurring in HA and NA. NA is targeted by the only available H5N1 antiviral, Tamiflu. The above report suggests that an H5N1 Tamiflu-resistant strain has evolved. Widespread use of Tamiflu will generate selection pressure for resistance. The comments above imply that such resistance is relatively easy for H5N1, since the number of H5N1 confirmed patients treated with Tamiflu has been exceedingly low. Tamiflu is the antiviral drug being stockpiled by many countries.
However, because surveillance of H5N1 in mild cases in northern Vietnam has been virtually absent, the possibility of Tamiflu treatment of mild human cases is quite real, since the drug has been approved for treatment and prevention of influenza. Widespread treatment with Tamiflu will likely generate widespread resistance.
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