H5N1 Tamiflu Resistance Re-emerges in Egypt
Recombinomics Commentary 16:58
January 3, 2008
The WHO has said some of those who died having contracted the H5N1 virus strain showed moderate resistance to Tamiflu, the antiviral drug.
The above comments indicate N294S has re-emerged in the Egypt. Almost exactly one year ago N294S was detected in the Gharbiya cluster. It reduced the efficiency of oseltamivir (Tamiflu) by 15-20 fold and was characterized by WHO as having “moderate” resistance because another resistance marker, H294Y, reduces efficiency by 1000 fold in patients in Vietnam.
However, the effectiveness of Tamiflu in the treatment of H5N1 is borderline, so a twenty fold reduction can lead to fatal infections. Since there have only been four recent confirmed fatalities in Egypt, at least half have H5N1 with moderate resistance, which is almost certainly due to N294S.
Last year H5N1 sequences were generated from two of the three cluster members. Samples had been collected prior to Tamiflu treatment, as well as 48 hours after treatment started (A/Egypt/14724-NAMRU3/2006 and A/Egypt/14724-NAMRU3/2006,). All four NA sequences had N294S, indicating the change was already present in the H5N1, which was probably in birds, based on the epidemiology of the cluster.
The presence of N294S in birds was supported by two prior isolates from China, A/duck/Zhejiang/bj/2002(H5N1) and A/Duck/Hong Kong/380.5/2001(H5N1), which had the same change. The change was not found in a limited survey of bird isolates in Egypt, and was not detected in any of the subsequent human isolates.
However, the new fatal cases this season raise the possibility that N294S has returned, and the comments above suggest that this is the case, since “some” patients have “moderate” resistance.
It is not clear if these infections involve the Gharbiya strain, detected a year ago, or the Uva Lake strain which has appended the N294S onto a new genetic background via recombination.
Release of the human and bird sequences in Egypt would be useful..
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