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D225G and D225N Diversity Confirmed in Fatal Utah Case
Recombinomics Commentary 22:22
December 11, 2009

A 28-year-old Utah woman who died this summer of H1N1 swine flu had a mutated form of the novel virus.

The state routinely sends samples to the CDC for it to sequence to look for significant mutations -- ones that would be resistant to the vaccine, for example.

That is not the case with the Utah mutation. Even if the mutated virus was passed from this woman to someone else, and there is no evidence it has, "the vaccine would still be protective," Herlihy said.

"Mutations occur very regularly in influenza," she said. "We are monitoring for genetic mutations of significance. We do not believe this is a genetic mutation of clinical significance."

The above comments confirm that A/Utah/42/2009 with D225G and D225N was from a fatal (28F) case.  However, the additional comments regarding significance and effect on the vaccine are curious.  The two receptor binding domain changes have been noted at increased frequencies since the summer and almost all cases were severe or fatal.  In Sao Paulo, D225G was identified in two patients and D225N was in two others and all four were fatal.  A case in China recovered after a month in the hospital and was described as the first severe cases in the province.  In Ukraine, Mill Hill sequenced H1N1 from four fatal cases, and all four had D225G.  The CDC sequenced two more, which were also likely to be from fatal cases, and both had D225N.  The Ukraine data was followed by a review of samples in Norway and three patients with D225G were identified. Two were fatal and one severe.  France also found two patients with D225G and both were fatal (and one also had H274Y).

The above confirmation extends the changes to the US and again involves a fatal case who was 28 and not said to have an underlying condition.

Although the CDC has placed these sequences on deposit, they have not released an antigenic characterization.  Similarly, the two samples from Ukraine were said to be California/7-like based on PCR instead of neutralizing titer generated by ferret reference sera.

Mill Hill tested one of the Ukraine sequences with D225G and classified it as a "low reactor" indicting the titer was at least four fold lower than the positive control, raising vaccine reactivity concerns.  Thus, the basis for the statement that the vaccine would "be protective" is unclear.

Similarly, after the WHO called the changes in sequences from fatal cases in Ukraine insignificant, the finding of D225G in dead and severe cases in Norway led to a revision of the "not significant" statement.

In June and July there was a spike in Utah deaths.  10% of the US fatalities in that timeframe were from Utah.  The presence of D225G and D225N in the above fatal case suggests that these changes were circulating in the area and may have contributed to the spike in fatalities.

Release of sequence data from samples collected at the site of infection, such as lung, would be useful.

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