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An Increase In US Influenza A Sequencing Is Overdue
Recombinomics Commentary 21:00
December 19, 2011

The latest confirmed trH3N2 case in West Virginia increases concerns that the number of novel flu cases in the United States is orders of magnitude higher than the 9 confirmed and 3 suspect cases in Maine, Iowa, Minnesota, and West Virginia.  Initial classification of these cases requires advanced PCR testing followed by sequencing, and the majority of lab confirmed cases do not go through this advanced testing.  In Maine and West Virginia, all PCR confirmed cases have been novel, suggesting there are hundreds or thousands of similar cases in those two states alone.  However, the confirmed cases in Iowa and Minnesota suggests similar numbers in those states, and there is little data to suggest cases are limited to those states since multiple novel cases have also been identified in Indiana and Pennsylvania.

The true geographic and genetic distribution of the cases has been limited by testing, which focused on cases with swine exposure during the off season, as well as initial cases for each state at the beginning of the current season.  Consequently, the number of public sequences from children under the age of 10 remains at 8 for this season, and 7 of the 8 were novel (excluding the most recent case, which has not yet been made public, but is rumored to be epidemiologically linked to the first trH3N2 case in West Virginia, A/West Virginia/06/11 (WV/06/11).

This case had an unusual constellation, which included an N2 not seen in the other 2010 or 2011 cases.  If epidemiologically linked, the new case will also have this N2, which is most commonly found in trH3N2 swine sequences, although link the N2 in the 2010 cases or the N2 in 2011 cases, it also links back to 2003 seasonal H3N2 (and the H in all 2010 and 2011 triple reassortant cases also links back to seasonal H3N2 in the mid 1990’s or 2003 seasonal H1N2.  These linkages to prior seasonal sequences may lead to milder infections in old patients, as well as low RNA levels in adolescents, especially those over the age of 10.  These factors also have a likely effect on the detection of the cases, especially in the early cases after the jump to humans.

The presence of clusters in four states, including an absence of swine exposure for all of the most recent cases, signals widespread and sustained transmission, which is largely undetected because of milder cases and limited testing.

The CDC has focused on swine exposure during the off season, and initial influenza A positives for each state at the beginning of the season, but they haves not issued a call for additional samples across the country, or published an increased number of sequences from cases under the age of ten, where the novel cases in 2011 have been concentrated. Instead surveillance has bee increased in small areas in Iowa and West Virginia.

Increased surveillance and sequencing of these samples throughout the country is long overdue.

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