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Records Set By New trH3N2 Contagion Cluster
Recombinomics Commentary 11:30
September 12, 2011

The recent cluster of trH3N2 cases in Indiana and Pennsylvania has led to a number of CDC publications describing these cases, but the reporting has led to confusion in the media and the creation / propagation in a number of media myths.  Although 8 confirmed cases of trH3N2 were reported for infections in 2009 (2 cases) and 2010 (6 cases), the cluster in 2011 has set new trH3N2 records in multiple categories and in triple reassortants in general if the 2009 H1N1 pandemic cases are excluded.  In addition to the 12 trH3N2 cases, there were 13 trH1 cases (12 trH1N1 and 1 trH1N2) reported prior to the 2009 pandemic.  Although all of the above are triple reassortants (tr), the pandemic H1N1 is readily distinguished from the 25 cases reported in the United States since 2005.

At the end of 2010 the CDC released sequences from the earlier tr cases, which indicated the human trH3N2 cases were clustering, although some similar swine isolates were reported.  The clustering of the human cases, in spite of increased swine surveillance raised concerns that the trH3N2 cases were transmitting in humans.
These concerns were increased when the WHO issued a pager alert on two cases, a child from Illinois (later identified by Wisconsin as an infect boy with CDC sequence designated A/Wisconsin/12/2010) and an adult from Pennsylvania (A/Pennsylvania/14/2010).  The alert created concerns, especially in eastern Europe, but concerns were reduced by statements indicating that the sequences were distinct and the trH3N2 was not spread in humans.  However, a subsequent case, who represented another Pennsylvania infection, A/Pennsylvania/40/2010, was reported in 2011 because of technical issues in growing the virus, which had been designated seasonal H3N2 because the human H3 and human N2 had produced a positive result with sub-typing reagents.  However, sequence data clearly showed that the virus was a trH3N2 and was closely related to WI/12/10.  Since both cases were infected within a week of each other, the close genetic relationship was a concern.  This concern increased when another case was identified in Minnesota, A/Minnesota/11/2010, was identified which was also closely related, and the daughter of the index case was serologically confirmed to have also been trH3N2 infected.  This cluster led to the creation of a pandemic vaccine target, using the sequence from the index case.

However, the “records” set by the above cases were broken by the latest cluster, which were initially reported by the release of sequences from an Indiana  sample collected July 24, 2011, A/Indiana/08/2011.  The CDC released the sequence after a new case was added to the MMWR in early August, which was initially assumed to be the daughter in the Minnesota cluster.  However, the July collection date of the Indian cas led to speculation that it had been the MMWR reported case, which remained unclear since the MMWR provided no detail.

However, when two more trH3N2 were reported in the week 34 MMWR, and one was from Indiana and the other from Pennsylvania, it became clear that 2nd 2011 case in the MMWR was another case from 2010, and the two cases reported in the same MMWR week were new and represented a record for reporting of trH3N2 cases, or triple reassortants in general, other than pandemic H1N1.  This record was quickly followed by another “first” when the PA Department of Health and then CDC via a “have you heard” media update indicated that there were two more trH3N2 cases from Pennsylvania, raising to three the number of trH3N2 cases linked to a single event, the agricultural fair in Washington County.
In addition to representing the largest number of confirmed cases linked to a single event, the sequencing of the isolates set additional records.  All four of the isolates from Indiana and Pennsylvania had acquired the M gene segment from pandemic H1N1 creating a new constellation of flu genes that had never been previously reported in humans or swine.  Moreover, all of the trH3N2 genes also matched, and the sequences from the three cases with no swine contact were virtually identical creating the largest cluster of identical tr confirmed sequences since the pandemic H1N1 outbreak.

Moreover, the H3 sequences from these cases were related to the 2010 cluster, but had evolved further away from seasonal H3N2 sequences, so two of the sequences have been reported as unsubtypable, the first such designations since the H1N1 pandemic.

In addition to these “records” a recent report indicated that the jump of pandemic H1N1 from swine to humans was tightly associated with the M gene segment, which now was in the 2011 trH3N2 isolates increasing concerns that the “first” were due to the more efficient transmission of trH3N2 in humans, resulting in a new contagion.

In spite of these new “records” and alarming acquisition, CDC reports continue to note the similarities between the result isolates with earlier cases and downplay the significance of these recent events with statements from CDC officials as well as statements noting sequence differences between the Schuylkill isolate and the Indiana isolate and not commentating on the identity between the sequences from cases without swine contact.

Thus, the statements in the week 34 FluView, the week 34 MMWR, and the latest “have you heard” on these four cases have generated an number of media myths on the historical perspective and pandemic potential in the latest cluster including .sequence relationships and links to swine contact as well as
the various recent records set.

Moreover, the request for samples from patients with flu symptoms and a swine connection adds to the confusion.  Instead of limiting samples, the CDC should be collecting as many influenza A samples as possible and PCR testing these an earlier samples to get a true picture of the number of trH3N2 cases in the recent and current samples collected by the CDC and state departments of health.

Testing on a par with PCR testing for pandemic H1N1 is long overdue for H3N2 or influenza A positive cases.

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