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Commentary

Lack of Contact Between trH3N2 Cases and Swine
Recombinomics Commentary 22:15
September 8, 2011

No direct exposure to swine was identified for this child; however, a caretaker reported direct contact with asymptomatic swine in the weeks before the boy's illness onset and provided care to the child 2 days before illness onset. No respiratory illness was identified in any of the child's family or close contacts, the boy's caretaker, or in the family or contacts of the caretaker.

All three of the patients were in the area where swine were exhibited and one had direct contact with swine.

The above comments described the four recent confirmed trH3N2 cases in Indiana and Pennsylvania.  As noted above, contact with swine was only identified for one of the four cases (2F from Schuylkill County who visited the fair on August 16).  Sequence data released yesterday by the CDC indicated that the trH3N2 isolates from each patient were virtually identical, even though there has been no reported epidemiological link between the cases.  The boy, A/Indiana/08/2011,  was infected in Indiana in July, while the collection dates for samples from the two girls were August 25, A/Pennsylvania/11/2011, and August 26 (previously reported as July 27), A/Pennsylvania/10/2011, well after the last day of the fair, August 20.  The samples were initially tested by the University of Pittsburgh Medical Center or the Pennsylvania Department of Health, respectively, suggesting independent infections.  The sequences from the Schuylkill patient had the same constellation of genes that had drifted slightly from the other three, again supporting an independent introduction and source.

However, although all four patients appear to have been infected independently, they were all infected by a trH3N2 related to earlier triple reassortant infections in humans.  Five of the genes are closely related to the 2010 trH3N2 infections in Wisconsin (A/Wisconsin/12/2010), Pennsylvania (A/Pennsylvania/40/2010) and a cluster in Minnesota (A/Minnesota/11/2010).  However, the new constellation has acquired a PB1 that is closely related to sequences from the tr H1N1 Huron Fair cluster (A/Ohio/01/2007 and A/Ohio/02/2007), an NA closely related to another trH3N2 Pennsylvania case, A/Pennsylvania/14/2010, and an M gene segment closely related to pandemic H1N1. 

Thus, the latest trH3N2 is the most common trH3N2 found in humans in 2010, which has acquired three gene segments previously linked to trH3N2 or trH1N1 human cases, signaling human adaptation, which includes the M gene segment which is critical for transmission in humans.

The identifies between the trH3N2 isolates from independent infections in Indiana and Pennsylvania, coupled with the acquisition of the M gene segment from pandemic H1N1, raises concerns that the trH3N2 is efficiently transmitting, especially in children, and is largely undetected because trH3N2 is largely limited to patients with a perceived or possible swine connection, which is reinforced the CDC request for samples from patients with flu-like symptoms who are exposed to swine.

Thus narrow search, will delay detection of widespread trrH3N2 which is expected based on the acquisition of H1N1 M gene and the identities between the four confirmed cases in Indiana and Pennsylvania.

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