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Commentary


trH3N2 Transmission In Pennsylvania?

Recombinomics Commentary 17:05
April 18, 2011

In addition to seasonal viruses, two unrelated infections with a swine origin influenza A/H3N2 virus have been identified in Pennsylvania with onset dates in September 2010 and October 2010. In recent years this virus has also produced human illness elsewhere in the country, generally in association with direct contact with ill pigs. It has not been associated with person-to-person transmission. Clinicians should remain alert to the possibility of infection with this virus in persons with influenza-like illness who have a history of recent exposure to swine populations, and collect appropriate diagnostic specimens.

The above alert and request concerning patients infected with an H3N2 triple reassortant (trH3N2) began appearing in weekly influenza reports from Pennsylvania at week 6.  However, the sequences released yesterday, Sunday, April 17, 2011 are inconsistent with multiple points implied by the above alert because the recently released sequence, A/Pennsylvania/40/2010 from the September case (3F) described above, is virtually identical to the September case (10 month M) from Wisconsin, A/Wisconsin/12/2010, which was the subject of the WHO pager alert on the Wisconsin September case and the Pennsylvania October case (46M), A/Pennsylvania/14/2010.

Thus, the above alert, as well as comments on the pager alert, are misleading because neither address the identity between the September cases, in Wisconsin and Pennsylvania, and instead compares the September cases to the October case (the pager alert compares the Wisconsin case to the later Pennsylvania case, while the Pennsylvania alert compares the two Pennsylvania cases).

As a result, both alerts claim that the September cases are linked to swine rather than each other, to maintain the claim that there is no human to human transmission of trH3N2.  Consequently, the above announcement requests samples from patients exposed to swine, leading to a strong bias against trH3N2 cases linked to human to human transmission, such as children like the two September cases, who would be most vulnerable to trH3N2, which have human H and N sequences from the 1990's.  Moreover, the trH3N2 sequences have D225G, and all of the recent cases have PB1 E618D.

In Pennsylvania there have been a large number of unsubtypable cases, and Pennsylvania leads the nation in reported influenza deaths.

Detection of trH3N2 in Pennsylvania is difficult, because as noted for the September case, it sub-typed as seasonal H3N2 and the 5 month delay in reporting the case was associated with the initial misdiagnosis coupled with a failure to isolate the virus.  The sequence released yesterday, 7 months after the fact, was from direct sequencing of the clinical samples.  However, it was released on a Sunday, absent the customary note citing the fact that the sequence was from a triple reassortant, which was included in the later case from Pennsylvania as well as the Wisconsin case (and all other  human trH3N2 sequences).

The failure of the CDC to address the identity between the two September cases, coupled with the technical issues associated with detection, and biased alerts, such as the one listed above for Pennsylvania, continue to increase trH3N2 pandemic concerns.
 
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