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H3N2v Heterogeneity Concerns In Jackson County Indiana
Recombinomics Commentary 17:00
August 22, 2012

The CDC has released three sets of H3N2v sequences from collections in July, 2012.  The first two sets included an isolate from Hawaii (A/Hawaii/03/2012), four isolates from the LaPorte County Fair (A/Indiana/06/2012, A/Indiana/07/2012, A/Indiana/08/2012, A/Indiana/09/2012), one isolate from Jackson County (A/Indiana/12/2012), and one isolate from the Butler County Fair (A/Ohio/13/2012).  All seven matched the novel sub-clade (A/West Virginia/06/2011 and A/West Virginia/07/2011) which was first reported at the Mineral County day care center, where there was no swine contact or exposure.  In addition to the two confirmed cases, 22 additional contacts of the index case had influenza-like illness, signaling efficient human to human transmission over a one month period at the day care center.

The four LaPorte sequences were identical, signaling rapid H3N2v transmission to all four cases.  In addition, at least 15 other fair attendees had ILI, again signaling efficient transmission. The LaPorte cases also had an NA acquisition, N234D, which abolished the glycosylation site  Although this change was not in the Jackson County sample or earlier collections of the novel sub-clade, it was in the Butler County isolate, A/Ohio/13/2012.

The third set of sequences released by the CDC where from four isolates from Indiana (A/Indiana/13/2012, A/Indiana/15/2012, A/Indiana/17/2012, A/Indiana/19/2012), while six were from Ohio (A/Ohio/14/2012, A/Ohio/15/2012, A/Ohio/16/2012, A/Ohio/17/2012, A/Ohio/18/2012, A/Ohio/20/2012).  The Ohio sequences were closely related or identical to the earlier Butler sequence, which again signaled rapid transmission (and all NA sequences also had N234D).

However, the Indiana sequences had considerable heterogeneity.  Two of the sequences (A/Indiana/13/2012 and A/Indiana/17/2012) were similar to, but distinct from the initial Jackson sequences (A/Indiana/12/2012).  The other two (A/Indiana/15/2012 and A/Indiana/19/2012) were virtually identical to each other and distinct from the 3 Indiana sequences above.  Most of these sequences were from Jackson County, while adjacent Jennings county was likely the fifth sequence, although one of the sequences may have been from Tipton County, which was also represented in the first 11July cases in Indiana.
The heterogeneity in the Jackson County sequences signaled divergence due to independent infections, which is consistent with reports that ILI was noted in Jackson County six weeks prior to the initial collection of samples, which was precipitated by the H3N2v positive cases linked to the LaPorte County Fair.

Community spread (or sustained community spread or efficient sustained community spread) have been denied by the CDC, but this lack of evidence is due to a lack of testing, which also highlights the factors involved in the generation of the pseudo-linkage of H3N2v with swine exposure (since virtually all testing is on samples from cases with swine exposure).

The heterogeneity in the Jackson County cases raises concerns that the ILI in the untested residents in Jackson County are common, and the decision of the CDC to begin testing ILI cases with no swine exposure.

However, the prior emphasis on linkage to swine exposure will limit the number of cases tested without swine exposure, which will delay a full understanding of the extent of human to human and community spread of the novel H3N2v first reported in late 2011 in West Virginia.

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