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Paradigm Shift Intervention Monitoring
trH3N2 Sequences To Genbank
The sequences have the corrected collection date for A/Pennsylvania/10/2011 (9F collected Aug 26), which follows A/Pennsylvania/11/2011 (9F collected Aug 25) and A/Pennsylvania/09/2011 (2F collected Aug 20).
The sequences from the Indiana case, A/Indiana/08/2011 (2M collected Jul 24) were also released at Genbank (released last month at GISAID).
Although the sequences are now easily accessed, the linkage to swine has yet to be established. Only one of the four cases has a link to swine contact, and no symptomatic swine have been identified at the Washington County fair or at the Indian location where the caretaker of the Indiana case had contact. Similarly in Indiana no contacts of the confirmed case have shown symptoms, abd no additional confirmations have been announced for Indiana after 6 weeks of investigation.
However, the sequences clearly point to human transmission. The sequences from the two most recent cases from Pennsylvania are virtually identical to each other and the sequences in Indiana. The sequences from the initial fair case (2F from Schuylkill County who visited the fair on Aug 16), has drifted from the other three sequences, signaling an independent event, but it still has the same constellation of genes seen in the other three cases, including a pandemic H1N1 M gene segment, which is critical for efficient transmission in humans..
Five of the other gene segments (PB2, PA, HA, NP, NS) are closely related to 2010 cases (A/Wisconsin/12/2010, A/Pennsylvania/40/2010, A/Minnesota/11/2010), including the cluster in Minnesota. The NA sequence is closely related to another Pennsylvania case, A/Pennsylvania/40/2010, as well as 2010 swine isolates from Pennsylvania (A/swine/Pennsylvania/62170-1/2010, A/swine/Pennsylvania/62170-2/2010, A/swine/Pennsylvania/62170-3/2010, and A/swine/Pennsylvania/62170-4/2011). The PB1 gene is closely related to sequences from the Huron County cluster in 2007 (A/Ohio/01/2007 and A/Ohio/02/2007), while the earlier trH3N2 cases are closely related to a more evolved version of this gene which have E618D, which is in virtually all pandemic H1N1 isolates.
Thus, the recent trH3N2 isolates continue to evolve from a sub-clade circulating in humans, which is rare in swine and not frequently detected, in spite of increased swine surveillance. The current constellation of genes, with 7 from prior trH3N2 cases and 1 from pandemic H1N1 has not been reported previously, and signals an adaptation to more efficient transmission in humans.
Thus, the CDC request for additional samples should extend to all children who are currently experiencing flu-like symptoms, especially if confirmed to be influenza A positive. This request should not be limited to those with swine contact.