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Silent Spread of  trH3N2 Raises Concerns
Recombinomics Commentary 13:00
September 9, 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.

The above comments from today’s MMWR have been cited as another example of human to human spread because the confirmed case had no contact with swine.  The interaction of the caretaker with swine is cited as a potential source of the infection, which would signal silent spread since the caretaker was asymptomatic, as were the swine.  Thus, the link between the confirmed cases and swine is purely speculative, because no symptoms were reported in contacts, and no trH3N2 was isolated from the swine or any contacts.

However, the sequences of the eight gene segments from the case (2M), A/Indiana/08/2011, defines a constellation of flu genes that has never been reported in swine.  Moreover, virtually identical sequences were found in two cases (both 9F) in Washington County, Pennsylvania (A/Pennsylvania/10/2011 and A/Pennsylvania/11/2011), as well as a closely related drift variant, A/Pennsylvania/09/2011, from a case (2F) from Schuylkill County in eastern Pennsylvania, who visited the western Pennsylvania fair on August 16.  However, like the case in Indiana, no symptomatic swine have been identified and no contacts have been lab confirmed.
All four of these isolates have the same constellation of genes, including those from 2010 human cases in Pennsylvania, Wisconsin, and Minnesota.  The Minnesota isolate. A/Minnesota/11/2010, was from the father of a second case who was trH3N2 lab confirmed, but had no contact with swine, representing another example of human to human transmission (and additional family members had flu-like symptoms, but serological testing was inconclusive).

These examples of human to human transmission, absence of swine contact in most of the recent cases, as well as the recent acquisition of the pandemic H1N1 M gene, which is critical for efficient human to human transmission, strongly suggest that the recent cases were not due to transmission from swine.  The two most recent cases had no known contact with swine and samples were collected five or six days after the Washington county fair ended, casting further doubt on a swine source,  The linkage to swine is largely linked to testing, since trH3N2 testing is focused on patients with swine association, as indicated in the latest CDC request for samples.

This requirement for a swine link has no scientific basis, and heavily biases the data, since symptomatic patients are rarely tested for trH3N2 if they have no swine connection. Instead these patients test positive for seasonal H3N2 because only an H3 sub-typing test is run, which has previously been positive for trH3N2 cases since the H3 and N2 trace back to a human infection of swine in the 1990’s (or 2003 for some N2 sequences).  However, the recently reported unsubtypable in week 33 in the updated FluView table suggests that in some instances the trH3N2 infections will not subtype.  The case from Schuylkill County represents the only confirmed trH3N2 collection in week 33, suggesting the H3 has evolved far enough away from the determinants recognized by the H3 typing reagents to produce an negative result in an influenza A positive sample.  The 2F case was influenza A positive, but confirmed with a PCR test directed against swine sequences.

Thus, prior and recent H3N2 cases should be PCR tested to begin to gain an understanding of the extent of trH3N2 spread. 

Currently Pennsylvania has the largest number of trH3n2 confirmed cases (five) and reported a large number of unsubtypables in the 2010/2011 season.  A retesting of these samples, as well as recent influenza A positive samples, with emphasis on those from children, would be useful.

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