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IHR Dates Based On CDC Reports Raise trH3N2 Concerns
Recombinomics Commentary 02:00
November 13, 2011

2011/11/2 Source: WHO Event Information Site for IHR National Focal Point

The United States this year, total 7 cases swine-derived H3N2 influenza cases so far in 2005 total of 15 cases.

The above translation is from the Taiwan CDC warning of travel to the United States due to the most recent trH3N2 cases, a veterinarian (59M) from Indiana, A/Indiana/10/2011 and a child (8M) from Maine, A/Maine/07/2011.  As noted above, the report of the two cases is from the WHO IHR site for reporting notifiable diseases, including novel influenza such as trH3N2, and the warning includes at tally of trH3N2 cases since 2005, which is incorrect.  The error is cited in the WHO update on pandemic vaccine targets, and both errors are almost certainly linked to a variety of CDC reports including the most recent "Have You Heard?" on the latest trH3N2 cases, which create confusion because the fact that all trH1 cases (12 trH1N1 and 1 trH1N2) were from cases prior to the 2009 H1N1 pandemic, while all reported trH3N2 cases in the United States are after the pandemic, beginning in August 2009 with a case in Kansas (A/Kansas/13/2009). 

This distinction is important because the human trH3N2 has emerged recently and quickly adapted to humans (large in late 2010) and was transmitting in 2011, based on phylogenetic analysis of all 8 gene segments from the human cases.

There were two additional cases (A/Iowa/16/2009 and A/Minnesota/09/2010) reported in the 12 months after the first case, but activity increased in late 2010 when WHO issued a pager alert citing cases in Illinois and Pennsylvania.  The subsequent description of these cases noted similarities with each other and the 3 earlier trH3N2 cases, but reports emphasized sequence difference, which signaled different sources and a lack of human transmission.  At the time full sequences from the first case were public, and similarities with swine sequences from an outbreak at the Huron County fair were noted because reports indicated the swine sequences and those from two confirmed cases, represented by A/Ohio/01/2007 and A/Ohio/02/2007 were noted (only the HA sequences from the human cases were public at the time).
However, the CDC then released sequences from all of the prior triple reassortant cases, including some classical swine cases from the mid-1990’s.  The triple reassortant cases, along with swine triple reassortant sequences which were generated due to increased swine surveillance, created a very clear picture of the relationship between the various isolates, which included clustering of human sequences.

One  example of clustering was signaled by the acquisition of E618D in PB1,  This polymorphism was in virtually all H1N1dpm09 sequences and was in the first trH3n2 sequence as well as all of the 2010 sequences.  The other polymorphisms generated a branch which included the Huron county sequences, but the 2010 sequence had evolved further and this branch initially only had human isolates.  Similar clustering was seen in other gene segments, including H3.  The first isolate in 2011 was A/Pennsylvania/40/2010, which was almost identical to A/Wisconsin/12/2010 in all eight genes segments as well several gene segments in A/Minnesota/11/2010, including H3.  Thus, most of the genes in most of the late 2010 human trH3n2 sequences matched, signaling human adaptation.

In 2011 the trH3N2 had evolved from the dominant 2010 sequences with matches in 5 gene segments (PB2, PA, HA, NP, NS).  The PB1 was an earlier version without E618D and close to the 2007 Huron County sequences.  The NA matched the only human isolate, A/Pennsylvania/14/2010, while the MP gene segment was from H1N1 pdm09.  Thus, the novel constellation was composed of gene segments that matched recent human isolates, and the identity in all 7 2011 isolates indicated the novel constellation was a human contagion that had jumped from swine to human to 2011.

Thus, the dates of origin (beginning in August 2009) as well as the phylogenetic analysis, were critical for the understanding of the emergence, and the incorrect dates cited above lead to misinterpretations such os the recent media and ProMed reports claiming that the 2011 isolates represented sporadic jumps from humans to people, which is based on heavily biased testing by the CDC and refuted by the evolution define by the sequences, the absence of the novel constellation from swine, the absence of any 2011 swine “exposure” involving symptomatic swine, and the identical constellation in all 7 2011 cases which represent independent infections in 3 states over a three month time frame.

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