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Commentary
Fatal Tamiflu
Resistance in Delaware
Recombinomics
Commentary 17:05
December 9, 2009
The above comments describe another fatal case of H1N1 swine flu in the United States. The Delaware case follows reports of clusters at the Duke Medical Center in North Carolina, a Virginia/Maryland cluster involving at least two patients at Johns Hopkins, and two cases in eastern Pennsylvania. These individual geographic clusters create one large cluster in the east coast since all states involved are contiguous.
Recent reports of resistance signaled the crossing of a tipping point. Human to human transmission was noted at Duke and Wales and WHO warned of a recent spike in cases. Similarly, the report rate by the CDC in the past three weeks is almost 10 fold higher than the prior weeks in the current season.
However, this explosion of cases has also been associated with fatalities, raising concerns that not only was the H1N1 with H274Y efficiently transmitted, but that it was lethal. At Duke the epidemiology supported human to human transmission and three of the four cases died, raising concerns that the H1N1 was more lethal. The Delaware case raises the number of fatal outcomes for the 10 recent cases to four. Similarly, the Netherlands has just reports its their fatality in six recent cases with H274Y, and France has indicated that one of the two fatal cases with D225G was also resistant.
The association of H274Y with a receptor binding domain change at position 225 was been reported previously. The first case of H274Y with associated Tamiflu treatment had D225E and a second cases with H274Y and D225E has recently been seen in Tennessee.
Thus, concerns that the transmission of H274Y has passed a tipping has been increased by the association of receptor binding domain changes with resistance as well as a trend toward fatal outcomes in these cases.
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