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Clusters of Tamiflu Resistance in the United States
Recombinomics Commentary 15:18
August 22, 2009

Of the four oseltamivir resistant 2009 influenza A (H1N1) viruses, two were original clinical samples detected by the neuraminidase inhibition assay, and two were viral isolates detected by sequence analysis of a neuraminidase gene.

The above comments from the latest CDC influenza weekly update describe four lab confirmed cases of oseltamivir resistance.  The two samples identified by sequence analysis appear to be the two immuno-suppressed cases in Seattle, since the MMWR dispatch mentioned H274Y and sequences from the two patients were released yesterday.  The two cases identified by the neuraminidase inhibition assay are likely the two North Carolina summer camp attendees who where recently described in media.  These two sets of clusters strongly suggest that the H274Y is not due to recent "spontaneous mutations", but instead represent minor species, which become major species shortly after the start of Tamiflu treatment.

It is unlikely that two attendees at the same summer camp would independently develop "spontaneous mutations" while on prophylactic Tamiflu.  It is more likely that both were infected with H1N1 containing H274Y, which became dominant after treatment.  These two cases are of concern, because many campers developed symptoms and may have carried the resistant H1N1 back to their town of residence.  These two cases attended camp in July, and many schools which began classes in August are now reporting large H1N1 outbreaks.  These outbreaks may be linked to Tamiflu resistance.  One of the Universities offered guidance for students who roommates on H1N1 students, which included prophylactic use of Relenza, signaling more concerns of Tamiflu resistance.

The number and size of outbreaks is remarkable (see map).  Although some officials have cited the fact that influenza A positive patients may not have swine flu, and some students have "normal flu" at this time of the year 99% of influenza A patients have swine flu.  Similarly, other officials cite colds and a "stomach virus" as causes of symptoms, by swine flu produces runny noses and gastro intestinal complications, so it is likely that the vast majority of students are infected with h1N1 swine flu.
However, the reports of Tamiflu resistance in summer campers in the area raise concerns that the spread is being fuel by Tamiflu resistance as well as the high frequency of swine H1N1 cases that do not have a fever.  This combination represent s a formula for a significant outbreak with far reaching effects.  Many of the middle schools, high schools, and Universities are experiencing an impact on athletic programs.  Reports of delays in football practices and games are widespread and signal the spread of the H1N1 in the student population.  Several school districts have close schools or plan closures, which are uncommon in the summer.

More information on the resistance in the campers, as well as samples collected before and after Tamiflu treatment of students would be useful.

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