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CDC Charade On trH3N2 Swine Exposure Raises Concerns
Recombinomics Commentary 17:45
November 2, 2011

Maine confirmed a second case of swine origin novel influenza A virus. The first case was confirmed on October 17th, and the second case was confirmed October 31st. Both cases had multiple exposures to pigs.

The above comments are from the Maine week 43 influenza surveillance report, and extends the number of 2011 trH3N2 cases with swine “exposure” to six, and it is likely that the seventh case (59M) will also have some sort of “exposure” raising concerns that the absence of cases without an exposure represents a charade which withholds such cases pending results of ongping epidemiological investigations.  All seven of the 2011 cases reported to date have the same constellation of flu genes, which has never been reported in swine in spite of increased swine surveillance and public sequences from swine isolates as recent as July, 2011.

The emergence of a trH3N2 human contagion was predicted by sequences from 2010 isolates, which were released after WHO issued a pager alert on two cases (in Illinois and Pennsylvania).  The pager alert created some concern, especially in eastern Europe, but the CDC noted that although both cases were H3N2 triple reassortants, sequence differences indicated the trH3N2 was not transmitting in humans.

However, the release of the sequences (at GISAID) revealed clustering of sequences and linkage to sequence isolate from a trH1N1 outbreak in Huron County, Ohio in 2007.  This outbreak yielded isolates from a presenter and her father (A/Ohio/01/2007 and A/Ohio/02/2007), which included internal genes which were precursors to the genes in the trH3N2 isolates.  Moreover, two dozen Huron fair attendees had flu-like symptoms, which are uncommon in August in Ohio, suggesting the trH1N1 spread well beyond the two confirmed cases.

The first trH3N2 case in the United States was from an infection two years after the Huron County outbreak.  The Kansas case, A/Kansas/13/2009, was followed by a case in Iowa, A/Iowa/16/2009, and one in Minnesota in early 2010, A/Minnesota/09/2010.  The isolates from the two cases in the pager report were A/Wisconsin/12/2010 and A/Pennsylvania/14/2010.  Just after the pager alert, a second case in Minnesota, A/Minnesota/11/2010 was reported, and additional cases in Minnesota were under investigation. The H3 sequence in the Minnesota isolate was closely related to the Wisconsin sequence, as were most of the other genes, which extended the clustering.

This trend was accelerated by the first two cases confirmed in 2011, which were cases that experienced significant reporting delays.  The first case (also from Pennsylvania) had developed symptoms less than a week prior to the Wisconsin case, but had been initially characterized as seasonal H3N2 and confirmation of trH3N2 was delayed due to technical issues linked to virus isolation.  Consequently, the case was reported 5 months after infection, and the sequence, A/Pennsylvania/40/2010, was closely related to the Wisconsin sequence, voiding the CDC assurances that followed the WHO pager alert.

The assurances were also voided by the second case reported in 2011, which was the daughter of the Minnesota case.  trH3N2 infection was lab confirmed by serological studies, which led to a six month delay in reporting.  The daughter had no swine contact, and represented the first lab confirmed examples of human transmission of trH3N2.  Like the Huron outbreak, the number of infections was likely markedly higher than the lab confirmed cases, because additional Minnesota family members had symptoms, but lab results were “inconclusive”.

Thus, the first two cases reported in 2011 strongly suggested that trH3N2 was transmitting based on sequence similarities between the cases in Pennsylvania, Wisconsin, and Minnesota, as well as lab confirmation of the Minnesota cluster.

However, the sequence data supporting human transmission was increased dramatically by the 2011 infections.  The first case reported was in Indiana and that case, A/Indiana/08/2011 also had no swine contact.  However, his caretaker had swine contact, but neither the caretaker nor the associated swine were symptomatic, and no evidence of SOIV infection has been reported.  The sequences from this case were novel.  Five of the gene segments, including H3, were closely related to the dominant sequence from 2010 (A/Pennsylvania/40/2010, A/Wisconsin/12/2010, A/Minnesota/11/2010, and the daughter of the Minnesota index case).  The NA gene however was closely related to the N2 of the other human case from late 2010, A/Pennsylvania/14/2010, while the PB1 gene was closely related to the sequence from the two confirmed 2007 cases in Ohio.

Of most interest however, was the M gene segment, which was acquired from H1N1pdm09, and this acquisition was of significant concern because a recent study indicated that the M gene was critical for the jump of H1N1pdm09 from swine to humans.  Moreover, this constellation of genes had not been reported in swine.

Concerns increased when the CDC issued an early release MMWR, which included the Indiana case as well as a case from Pennsylvania, A/Pennsylvania/09/2011, which had the same constellation of genes.  It was a drift variant, so the CDC noted that the same source for the Indiana and Pennsylvania was unlikely because of minor sequence differences.  However, these assurances were voided by two more cases from Pennsylvania (A/Pennsylvania/10/2011 and A/Pennsylvania/11/2011), who like the first case had attended the Washington County fair.  These sequences matched each other, as well as the Indiana case, supporting human transmission.  Moreover, although swine were exhibited at the fair, there were no reports of symptomatic swine or identification of SOIV infection.

The emergence of a new human contagion was supported further by the first case in Maine (8M), which had a matching constellation of genes a seen in A/Maine/06/2011.  Swine exposure at an agricultural fair (likely the Cumberland County fair) was again cited, but no symptomatic swine were reported.  That case was followed by another case from Maine, A/Maine/07/2011, and Indiana, A/Indiana/11/2011 which were also from patients infected in October by trH3N2 related to each other and the first Maine case.

Thus, all seven 2011 cases have the same constellation of genes which has not been reported in any swine.  In spite of this strong evidence of human transmission, all reported cases have a loose “swine exposure” component, suggesting cases without a swine exposure are being withheld pending epidemiological investigations.

trH3N2 cases without some sort of swine exposure, would confirm widespread human transmission and the start of a new pandemic, and this announcement has been delayed by the charade that releases sequences from cases with a swine exposure, and delays confirmation of cases without an exposure.

Details on suspect trH3N2 cases under investigation are long overdue.

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