H1N1 Duke Death Cluster With H274Y and D225G/N
Recombinomics Commentary 17:15
January 26, 2010

In the USA outbreak, which involved four severely immuno-compromised patients, cases occurred in a two-week period between mid-October and early November. Three of the four cases were fatal, but the role of H1N1 infection in contributing to these deaths is uncertain.

The above comments describe a fatal H1N1 cluster with H274Y at Duke Medical Center.  Although the outbreak was in October / November, it was not announced until December.  Fatal clusters of H1N1 cases, especially with H274Y are cause for concern.  The clustering of deaths raised concerns that the patients had D225G and/or D225N, which has been linked to fatal cases.  In Ukraine D225G, D225N or both have been found in 30 patients and 29 were fatal.

The CDC has released sequences (at GISAID) from the above cluster, which had H274Y.  One HA sequence, A/North Carolina/39/2009, had D225G (as a mixture with wild type).  Another sequence, A/North Carolina/42/2009, had D225N (as a mixture with wild type), raising concerns of coupling of H274Y with receptor binding domain changes, which was a precursor to the fixing of H274Y in H1N1 seasonal flu through hitchhiking and recombination.

NOTE:  A third sequence, A/North Carolina/49/2009, has D225G (and H274Y).  It is likely that the three sequences with D225G/N were from the three fatal cases.

Although WHO issued a December 2 update on the cluster, there was no mention of the receptor binding domain changes.  The D225G report in the WHO Weekly Epidemiological Record mentions three instances of D225G with H274Y.  This combination has been reported in France and in Illinois in the United States.  The cluster at Duke Medical Center would represent a third example, but this example was in the context of another patient with D225N and H274Y transmission, and it seems likely that the two examples of D225G/N were in the three fatal cases at the medical center.

The increasing appearance of D225G/N in fatal cases, including the high frequencies in Ukraine and Russia continue to cause for concern.

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