Robert Roos * News Editor

Mar 4, 2010 (CIDRAP News) – Norwegian scientists today reported a pandemic H1N1 virus mutation that appears to be associated with severe disease, but a leading US flu expert said global data on the mutation don’t show a clear connection with severe illness.

A team from the Norwegian Institute of Public Health in Oslo reports that it found the mutation in 11 of 61 severe illness cases that were analyzed between July and December 2009. The mutation was not found in any of 205 mild cases that were analyzed between May 2009 and January 2010.

“This difference is statistically significant and our data are consistent with a possible relationship between this mutation and the clinical outcome,” says the report by A. Kilander and colleagues, published today in Eurosurveillance. “To our knowledge, this is the first identification of a change in the pandemic virus that correlates with a severe clinical outcome.”

However, Dr. Nancy Cox, director of the Influenza Division at the US Centers for Disease Control and Prevention (CDC), said global H1N1 data so far do not show a clear association between the mutation and severe illness.


Recombinomics: Association of D225G/N With Severe H1N1 Cases In Norway

Here we report the occurrence of an amino acid substitution, aspartic acid to glycine in position 222 (D222G) in the HA1 subunit of the viral haemagglutinin, in clinical specimens from 11 out of 61 cases analysed in Norway with severe outcome. Such mutants were not observed in any of 205 mild cases investigated (Table), thus the frequency of this mutation was significantly higher in severe (including fatal) cases (p<0.001, Fisher’s exact test, two-sided) than in mild cases. D222G mutants were detected throughout the sampling period, from the first recorded severe cases in July until early December. The frequency of another substitution in the same position, D222E, did not differ significantly between mild and severe cases (p=0.772). Yet another substitution, D222N, was observed in a very few cases (n=4), and at a higher rate than expected among severe cases (three of four cases, p=0.039). The wild type 222D was, not surprisingly, significantly less frequent in severe than in mild cases (p<0.001).

In several of the patients where D222G mutant viruses were found, they coexisted with wildtype 222D viruses. Further analysis of this phenomenon is ongoing.

The above comments from a report from Norway in Eurosurveillance confirm that D225G/N (H3 numbering) is significantly more common in severe cases in Norway.  These data support sequences released by Mill Hill from fatal cases in Ukraine, as well as fatal cases in Russia, which raises concerns that a third wave with a higher frequency of D225G/N would produce a higher incidence of severe and fatal cases.  This concern is increased by the designation of a Ukraine isolate with D225G as a low reactor.


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