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WHO History Report On trH3N2 Raises Concerns
Recombinomics Commentary 14:00
November 9, 2011

Swine-Origin Influenza A(H3N2)
Swine influenza A(H3N2) viruses are enzootic in swine herds of North America and other parts of the world. Characterisation of recent A(H3N2) viruses from swine in North America indicates that their HA genes have evolved from the human virus precursors that circulated in the mid-1990s. Isolation of swine-origin influenza viruses (SOIV) A(H3N2) from humans has been reported infrequently. The United States of America reported eight infections due to A(H3N2) SOIV between January 2005 and 15 February 2011.

A(H3N2) SOIV infections from 16 February 2011 to 19 September 2011
There have been four human infections with A(H3N2) SOIV in the states of Indiana (1) and Pennsylvania (3), United States of America, in this period. The HA and neuraminidase genes of these four viruses were similar to those of swine viruses that circulate in the United States of America. Sequencing data indicated that the matrix genes of these viruses were acquired from an A(H1N1)pdm09 virus, unlike SOIV isolates from previous human cases.

The above comments are from the WHO update on pandemic influenza vaccine targets.  The update appears to have taken some of the information from the CDC website on SOIV in humans since 2005.  That website presented very fuzzy data on the history of US cases (which has been recently clarified), which then was extended and misrepresented in the above WHO comments. Although the first triple reassortant case in the US was in 2005, all 13 H1 cases (twelve H1N1 and one H1N2) were prior to the 2009 swine flu pandemic.  The first US (SOIV)H3N2 case was in 2009 (A/Kansas/13/2009), which was followed by a second case in 2009 (A/Iowa/16/2009) and 6 cases in 2010 (A/Minnesota/09/2010, A/Pennsylvania/40/2010, A/Wisconsin/12/20110, A/Pennsylvania/14/2010, A/Minnesota/11/2010, daughter of A/Minnesota/11/2010).  Thus, the 8 cases were in a period of just more than one year, and not the 6 years cited above.  Reporting of the first Pennsylvania case was delayed 5 months and the reporting of the sequence was delayed 6 months.  The reporting of daughter of the Index case for the Minnesota cluster was delayed 6 months, and was after The February 15, 2011 cited above.

Similarly, the first reported case with an M gene from H1N1 was from an infection in late July, so the 2011 cases were reported over a 2 month time period prior to the report, and there were 3 more October cases, bring the total number of reported cases to seven over a three month period. Moreover, the first 2011 case had no swine exposure.  The CDC speculated that the case was infected by his caretaker, who had swine exposure, but neither the caretaker nor associated swine had symptoms, and no SOIV has been reported in either.

Thus, the first three cases reported in 2011 supported human to human transmission.  The Pennsylvania sequence matched the Wisconsin sequence in all 8 gene segments.  The Minnesota case lab confirmed human to human transmission in the cluster, and suggested the symptomatic contacts who tested “inconclusive” were also trH3N2 infected.  The first trH3N2 case in 2011 had no swine exposure and was acknowledged to be due to human to human transmission.  Moreover, the constellation of flu genes had never been reported in swine, and was matched by the next six trH3N2 cases in 2011.  Thus, all seven 2011 cases have the same constellation of genes which has never been reported in swine.

In spite of the overwhelming evidence for human to human transmission, the CDC early release MMWR requested samples from cases with a swine exposure, further biasing the testing for trH3N2.  This bias was extended by the Maine CDC who claimed that all 2011 trH3N2 cases had a swine exposure (which was in the advisory associated with the first October case in Maine).  Similarly, the Indiana DoH claimed that there was no novel influenza circulating in Indiana, even though the only PCR confirmed cases in week 43 was trH3N2, and this isolate was only the second confirmed flu cases in the first month of the 2011/2012 flu season (weeks 40-43).  Thus, the trH3N2 case represented 100% of the PCR confirmed cases in Indiana week 43, and 50% of confirmed cases in the 2011/2012 season.

The WHO summary also does not note the relationship of the 2011 isolates to the 2010 sequences.  However, Table 7 lists the ability of the four trH3N2 antisera (A/Kansas/13/2009, A/Wisconsin/12/2010, A/Pennsylvania/12/20110, and A/Minnesota/11/2010) to recognize the first trH3N2 from 2011, A/Indiana/06/2011.  The recognition is high because the H3 is closely related to the targets from Wisconsin and Minnesota, while the N2 is closely related to the isolate from Pennsylvania.
The September publication confirmed that Minnesota/11/2010 was the pandemic H3N2 vaccine target, as suggested by the release of sequences in August, and the September report was e-mailed to WER subscribers on October 21 (but was not updated to reflect the three confirmed October cases.

The two most recent October cases were the subject of reports in the media and ProMED, which noted the development of seed stocks, which were largely ignored, due in part to the representations in the CDC and WHO reports, which focused on swine exposure minimized the significance of the sequence matches, the Minnesota cluster, the lack of swine exposure in the first reported 2011 trH3N2 case, and the absence of the human contagion constellation in swine.

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