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Casual trH3N2 Transmission In Pennsylvania
Recombinomics Commentary 14:20
February 6, 2011

No contact with pigs has been identified in the Pennsylvania case in the week before symptom onset on October 24, 2010; however the case lives in an area close to pig farms.
The above comment is from the CDC week 44 FluView describing one of the new cases associated with the WHO pager altert on novel trH3N2 in the United States.  As noted above the Pennsylvania case denied contact with swine prior to development of symptoms on October 24, 2010.  The USDA has released two HA sequences from swine isolates in Pennsylvania collected on October 25, 2010.  The two swine sequences, A/swine/Pennsylvania/62170-1/2010 and A/swine/Pennsylvania/62170-3/2010 were identical to each other and virtually identical to three sequences (original and virus grown in mammalian cells or eggs), A/Pennsylvania/14/2010, collected from the above patient (45M).  These Pennsylvania swine sequences are much closer to the Pennsylvania patient than other trH3N2 sequences from swine or patients, clearly demonstrating a close association between the Pennsylvania swine and human sequences, signaling transmission.

However, the denial of swine contact by the patient leaves open the direction of the transmission, as well as the route.  The PB1 from the human Pennsylvania isolate had E618D, which has not been seen in any prior swine H3N2 sequences, but is in the first human trH3N2 sequence reported in the US, Kansas/13/2009, as well as all 2010 human trH3N2 sequences (A/Minnesota/09/2010, A/Wisconsin/12/2010, A/Minnesota/11/2010) indicating it is a recent acquisition and may represent a human adaptation since it is virtually all pH1N1 sequences (human or swine).  Its presence or absence in the Pennsylvania swine is not public, but it is likely present, regardless of the direction or route of transmission because once the marker appears in human cases, transmission back to swine is likely, as was seen for pH1N1 which has now been identified in swine worldwide and the recent swine H1 isolates have PB1 E618D.

Thus, the direction of the transmission remains unclear, but the denial of contact with swine suggests transmission is casual and may involve additional human cases linking the reported Pennsylvania case to the Pennsylvania swine, which were presumably in the nearby pig farms described above.

This casual transmission suggests that swine trH3N2 is far more common than the seven cases reported to date, and the additional cases involve human to human transmission, which would not be unexpected sine the H3 and N2 trace back to seasonal H3N2 circulation in the 1990’s.  As noted in the week 4 FluView, the second trH3N2 case in Pennsylvania was initially classified as seasonal H3N2 and was changes to swine trH3N2 base on PCR analysis during routine characterization, which was reported 5 months after the fact (the second Pennsylvania case developed symptoms on September 6, 2010, but was not reported until February, 2011 because of a failure to grow the virus).

The number of trH3N2 cases in Pennsylvania is also unclear because of the large number of cases classified as seasonal H3N2 as well as the large number of isolates classified as unsubtypable.

More information on trH3N2 cases under investigation, as well as release of a partial sequence from the second reported case in Pennsylvania as well as the locations of the two Pennsylvania cases would be useful.

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