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N294S Tamiflu Resistance in Gharbiya Cluster
January 18, 2007
The health organization emphasized that it was too early to tell whether the resistant strain had developed independently in the two patients, who were both under treatment with the drug, or whether they had picked it up from birds or from each other. The resistant strain did not spread to anyone else, including a third family member who also had avian flu.
“Given the information we have, we don’t see any broad public health implications,” said Dick Thompson, a spokesman for the organization.
The above comments acknowledge the Tamiflu resistance in two members of the Gharbiya cluster, however, circumstantial data strongly suggests that the change, N294S, developed prior to treatment of the cluster members with Tamiflu.
The NA sequence from the two cluster members, as well as the October case, have been submitted to Genbank by NAMRU-3, and assigned accession numbers, EF222322-EF222324. The HA sequences from these patients has already been released at Genbank. There is no sequence from the third cluster member, because H5N1 was not isolated from the index case. However, the N294S was found in the two NA sequences that were submitted, and the changes have been independently confirmed by the CDC in Atlanta. The samples were collected within 48 hours of treatment, so it is unlikely that all four sequences (two from each patient) became so dominant so shortly after the start of treatment in both patients.
Additional samples are being collected from birds in Egypt, as well as the most recent confirmed case. These sequences will address how widespread the change is. However, the data to date suggests these changes were present prior to the start of treatment. There is no data in the literature indicating N294S lacks fitness.