Is H1N1 Vaccine Mismatch Driving Tamiflu Resistance?
Recombinomics Commentary 16:49
February 17, 2008
H3N2 strains are treatable by Tamiflu and other antiviral drugs, but the other, H1N1 Type A strains are more resistant. Of all flu samples tested this year, 4.6 percent have been resistant to antiviral medications. That's up from fewer than 1 percent last year.
The above comments on the jump in seasonal flu infections miss the main point on the Tamiflu resistance. Although 4.6 percent Tamiflu resistance on all flu cases in the United States is accurate, all of the reported resistance has been H274Y in H1N1, so the level of resistance in H1N1 is 8.2%. However, this number is trailing the actual number, because many of the more recent cases have not been serotyped, and many of the H1N1 isolates have not been sequenced. Last week the State of Illinois issued a health alert because ten isolates from Chicago were Tamiflu resistant, and 8 of the 10 were from a single health care facility. Since the 8.2% represent only 16 cases, the 10 new cases could dramatically increase the percent positive.
Similarly, the percent positive in Europe for H274Y is above 20%, with frequencies as high as 66.3% in Norway (63 of 95 isolates). These high levels in Europe and in countries where Tamiflu use is not common suggest that the H1N1 containing H274Y is evolutionarily fit, and initial data indicate it is present in the Brisbane/59 strain ,which is not a good match for the H1N1 component (Solomon Island) in the current northern hemisphere vaccine.
Thus, the current vaccine mismatch may enhance the spread of H1N1 with H274Y in cases where H274Y is in the Brisbane/59 strain.
The sudden appearance of H274Y has startled influenza experts, who previously had viewed H274Y as an adoptive mutation that would spread in populations under treatment with Tamiflu. The spread of H274Y in the absence of Tamiflu may in fact be facilitated by the poorly matched vaccine which kills Solomon Island H1N1, eliminating the competition of Brisbane/59 with H274Y, which has been noted in Hawaii, France, and Norway. Thus, the poor recognition of Brisbane/59 allows it to become the dominant strain, and the presence of H274Y on the Brisbane strain in countries with high levels of resistance may not be a coincidence.
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