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CDC Human / Swine H3N2v Discordance Caught On Tape
Recombinomics Commentary 19:30
September 12, 2012

Public health officials provide the latest update on the H3N2, the new strain of influenza that appears to have jumped from swine to humans and has already infected nearly 300 people in the United States.

The above summary for the Lyn Finelli CDC presentation, ““Emergence of Animal-Origin H3N2 Influenza” at the ASM ICAAC meeting in San Francisco contains the word “appears,” but the presentation (video and audio available here) failed to address the glaring discordance between the H3N2v sequences from the 2012 cases which were generated by the CDC and the swine H3N2v sequences generated by the USDA.

The sequence data was indirectly addressed by a question from Helen Branswell after Lyn Finelli noted an increase in the frequency of H3N2v in swine isolates.  Branswell asked if the recent swine H3N2v cases had the H1N1pdm09 M gene, which was present in all 2011 and 2012 human cases, but Finelli had no answer.

However, the USDA data, which has been posted on the CDC and USDA websites, notes that in FY2012 (beginning on October 1, 2011) the USDA identified 138 H3N2v swine cases, and 57 had an H1N1pdm09 M gene (called H3N2pM on both sites).  Thus, although the number of H3N2v swine cases in FY2012 was higher than the 73 H3N2v swine cases in FY2011, most of the FY2012 cases did not have H1N1pdm09 M gene.  In fact the 81 swine cases without the H1N1pdm09 M gene were higher than the total for FY2011.

The discordance between the human and swine cases was glaring when the H3N2pM swine cases were compared to the human cases.  In 2011 the first human H3N2pM case was identified in July in Indiana.  The constellation and lineages for the 8 gene segments was novel.  Five of the genes (PB2, PA, HA, NP, NS) matched the dominant human sequences for H3N2v cases in 2010, while the other three gene segments (PB1, NA, MP) matched H1N2v cases such as found in the Ohio isolate, A/swine/Ohio/10-1/2010.  This combination was novel and has not been found in any swine sample collected prior to the human cases.  The first 10 human cases in 2011 matched Indiana isolate in all 8 gene segments, which included the H1N1pdm09 M gene.  Included were the three isolates from Iowa in November, which had no swine exposure.

However, the remaining cases for 2011 were also from a cluster with no swine exposure.  The West Virginia sequences matched the early 10 human cases in 7 of the 8 gene segments.  However, the N2 was not from an H1N2 lineage, but instead was from a swine H3N2 lineage.  These two N2 lineages were easily distinguished.  The West Virginia cluster created considerable concern, because in addition to the two confirmed cases, 22 additional contacts of the index case had influenza-like illness and the time gap between the two confirmed case was too large to support direct transmission.  Moreover, the disease onset dates indicated the H3N2v was transmitting at the day care center for 3-4 weeks.  As`was seen for the Indiana case, the West Virginia sub-clade was novel and had not been reported in swine previously.

The first human H3N2v case in 2012 was from Utah and it had the same constellation as the West Virginia cluster.  That case was followed by an explosion of cases in July and August in multiple states (Hawaii, Indiana, Ohio, Kentucky, Illinois, West Virginia, Wisconsin, Minnesota, Pennsylvania, Maryland, Minnesota).  The CDC has released 50 sets of sequences from these human cases and all are closely related to each other and match the 2011 West Virginia sub-clade.

A large number of swine sequences have been made public, including the 57 FY2012 cases cited at the USDA website.  24 of these H3N2pM case match the human cases.  Thus, most (33) of the H3N2pM swine sequences don’t match the human 2011 and 2012 cases and have never caused a reported human cases.  Moreover, only two of the 24 swine matches have the constellation seen in 2012 cases.  Thus, only 2 of the 138 swine H3N2v cases in FY2012 have a sequence that corresponds to the 2012 human cases.

In addition, the common sub-clade, represented by 22 of the 24 matches, has not cause a reported human case in 2012.

The CDC has yet to acknowledge the difference in the N2 lineages for the intial 2011 human cases and all 2012 human cases or the dramatic discordance between human and swine sequences.

Moreover, the USDA has released sequences (HA, NA. MP) from one of the 12 swine H3N2pM cases from the LaPorte County fair and although the N2 sequence matched the lineage for the 2012 human cases, the swine sequence was easily distinguished from the four human H3N2v sequences from LaPorte County, Indiana, signaling human to swine transmission.

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