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Transmission of N294S Tamiflu Resistance In Egypt
Recombinomics Commentary
January 19, 2007

Current laboratory testing suggests that the level of reduced susceptibility is moderate. This mutation has previously been identified in Viet Nam in one case in 2005

The above comments from the WHO update on the N294S Tamiflu resistance markers in the Gharbiya cluster, describe a patient (14F) in Hanoi in 2005, who developed Tamiflu resistance via two markers, H274Y and N294S.  H274Y was present at higher levels and was associated with a high level of Tamiflu inhibition in vitro, indicating the clinical role of N294S in that patient was minimal.  The above case further suggests that the two patients in the Gharbiya cluster were infected with H5N1 that had already acquired N294S.

The evidence for N294S prior to Tamiflu use is significant.  The NA sequences generated by US NAMRU-3 were from direct sequencing of samples collected two days after the start of Tamiflu treatment (2 X 75 mg).  The two sequences had no evidence of the wild type N at position 294 or the common change associated with Tamiflu resistance in H5N1 infected patients, H274Y.  Since all four cluster members developed symptoms prior to Tamiflu treatment of any cluster member, the N294S would have had to have arisen independently in each patient. Moreover, N294S has been found in H5N1 infected ducks in China (Zhejiang and Hong Kong).

Therefore, the likelihood that N294S independently arose in both patients in response to Tamiflu treatment remains low.

Further testing of H5N1 patients and birds in Egypt will provide information of the frequency of N294S in Qinghai H5N1 in the region.

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