Frequency of N294S Tamiflu Resistance in Egypt
Recombinomics Commentary
January 28, 2007
Mutation in the viruses of these two patients cannot be extrapolated to mean that Tamiflu has lost its effectiveness in other patients in Egypt or elsewhere.
It has not.
The above statement issued by the WHO Regional Office for the Eastern Mediterranean, includes the blanket statement that Tamiflu has not lost its effectiveness for other patients in Egypt or elsewhere, suggesting that there are data to support the statement. However, such data has not been made public.
Most sequences that have been released have been from early collections from patients, which are collected either prior to Tamiflu treatment or shortly thereafter. Although the samples from the Gharbiya cluster strongly indicated that the resistance due to N294S existed prior to treatment, the results raise questions about Tamiflu resistance emerging during treatment. Such development has been demonstrated for H274Y, but similar resistance in Egypt has not been evaluated.
The data from the Gharbiya cluster string suggests N294S is present in H5N1 circulating in Egypt. Sequencing of bird isolates in the region are necessary to determine the distribution of N294S in the region. However, the testing to date does not rule out the presence of N294S as a minor component in the patients, which is not readily apparent until the minor component emerges because of the selection pressure of the Tamiflu treatment.
This issue can be most easily addressed by sequencing of samples collected several days after the start of Tamiflu treatment. In Egypt, all five of the confirmed patients this season have died, as have the last four cases from last season, although all patients have been treated with Tamiflu.
Similarly, the recent patients have also acquired M230I, which is adjacent to the HA receptor binding domain. This change is present in all three human influenza strains, H1N1, H3N2, and influenza B. The change creates a region of identity with positions 226-230 (QSGRI) of influenza B. M230I is also present in isolates such as H3N8 in dogs and H7 isolates in outbreaks in the Netherlands (H7N7), Canada (H7N3), and England (H7N3). All three outbreaks were linked to one or more human infections.
Thus, the cause of the high case fatality rate remains to be determined.
However, the public data does not exclude the emergence of Tamiflu resistance in other patients in Egypt or elsewhere.
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