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West Virginia H3N2v Cluster N2 Recombination
Recombinomics Commentary 23:55
January 5, 2012

More recently, investigation of a case in West Virginia has identified a possible outbreak, with 23 out of 70 contacts of the case reporting ILI; all have recovered.

The above comments are in the California Department of Public Health December 15 advisory, which followed the December 9 release of the sequences for the index case of the Mineral County cluster, A/West Virginia/06/2011.  The cluster was under investigation and the West Virginia Department of Health had tested a sample from a symptomatic contact.  However, shipment of the sample had been delayed and the test result was a weak positive for influenza A, and listed as influenza A in the West Virginia week 48 report on December 16.  Thus, when the advisory was issued, the index case had been trH3N2 confirmed, and the contact. A/West Virginia/07/2011, was influenza A positive.  The confirmed cluster was the reported in a December 23 early release MMWR, which will be reported again in tomorrow’s MMWR.

The MMWR report provide detail on disease onset dates, which indicated the virus circulated for almost a month, and involved additional symptomatic cases.  However, the report did not indicate 23/70 contacts were symptomatic, and instead maintained that there was no sustained or community transmission.

The CDC also released a series of additional documents associated with the MMWR, including simplified terminology for each novel serotype.  The trH3N2, trH1N2, and trH1N1 cases would be designated H3N2v, H1N2v, and H1N1v respectively. In part because and H1N1v case (A/Wisconsin/28/2011) was reported along with the West Virginia contact
(A/West Virginia/07/2011) report, and an H1N2v case (A/Minnesota/19/2011) was reported with the West Virginia index case (A/West Virginia/06/2011) . The H1N2v case also had no swine contact and was generated with the same parental viruses (human trH3N2 from 2010 and a swine H1N2 from Ohio).  Consequently, the N2 for the first 10 H3N2v cases in 2011 and the H1N2v case was the same.

However, the N2 in the West Virginia cluster was from a lineage that was predominantly in H3N2 swine, although swine trH1N2 and trH3N2 have an H2 that is human and traces back to seasonal H3N2 from 2003.
Analysis of the N2 sequences indicates that A/West Virginia/06/2011 and A/West Virginia/07/2011 are virtually identical (differ at two positions) and both have acquired tandem non-synonymous polymorphisms L370S and S372L from seasonal H3N2 (in sequences from isolates from 2006-2011 via recombination (in addition to synonymous acquisitions from the N2 sequences from the trH1N2 lineage.

The acquisition of the two seasonal polymorphisms raise concerns that the H3N2v in West Virginia has adapted to generate the high attack rate seen at the Mineral County day care facility.

The are anecdotal reports of widespread ILI in northern California as well as a lab confirmed H3N2v in Napa County California, which is being investigated by the CDC.  Details on the relationship of this Napa County case to the ILI cases and sequence relationship to the West Virginia cluster would be useful.

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