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Commentary
Fatal H3N2v
With H1N1pdm09 M Gene In Kansas Swine
Recombinomics Commentary 18:30
December 27, 2011
The above comments, from a recent paper entitled “Emergence of novel reassortant H3N2 swine influenza viruses with the 2009 pandemic H1N1 genes in the United States” describe multiple swine outbreaks on farms in Kansas associated with H3N2v (trH3N2) with an H1N1pdm09 M gene. Although the paper was published on December 24, 2011, the sequences associated with the outbreaks were released at Genbank at the end of November, and discussed in detail.
The sequences were of interest because the HA genes were closely related to a series of sequences released by the USDA October 1. The USDA sequences included HA, NA, and M genes, and one series from 2011 isolates from Texas and Iowa had an H1N1pdm09 M gene. However, they were not matches for the human H3N2v (H3N2pdm11) cases because the HA sequences were distinct. The Kansas sequences represented all 8 gene segments, which indicated the isolates have 3-5 gene segments that matched H1N1pdm09, highlighting additional differences with the human cases as seen in phylogenetic trees for PB2 and PB1 here, PA and HA here, NA and NP here, or MP and NS here.
Similarly, two 2010 isolates from Iowa also had an H1N1pdm09 M gene, but they also had a distinct HA sequences. The USDA subsequently released the internal genes, which like the human cases were all linked to swine reassortant sequences, but the internal genes were also distinct.
Thus, even though the USDA had released sequences (primarily HA, NA, MP) from 150 isolates collected between 2009 and mid-2011, and 30 were H3N2v, which included 8 with an H1N1pdm09 M gene, none matched the first 10 human sequences, which matched each other in all eight gene segments.
On November 20 the USDA released one additional sequence. In contrast to earlier releases, this isolate was the sole release, and the sequence represented all eight gene segments. Unlike earlier isolates with an H1N1pdm09 M gene, this isolate had an HA gene that matched the human 2011 isolates, which was also true for all 6 other genes, representing a match for all 8 gene segments. However, this isolate, A/swine/NY/A01104005/2011, was collected on September 13, which is after the initial human isolates from Indiana and Pennsylvania, which were from July and August collections.
Thus, no public swine isolate collected prior to the human cases matches the human isolates, and the New York swine is the only public match. Moreover, it was from an anonymous sample collected under the USDA program which offers anonymous testing, and therefore almost certainly represents a sample from a symptomatic swine. Thus, in spite of causing symptoms, which are likely similar to those described above, the USDA program, and all other surveillance programs, failed to report a match from a sample collected prior to the 2011 human cases in July and August.
In spite of this well known failure, CIDRAP put out a report on November 29 citing the 30 H3N2v swine cases, including 8 with H1N1pdm09 M gene identified under an “informal analysis”. Identical numbers identified through an “informal analysis”, was included in the CDC’s early release MMWR published on December 23, which was then noted in a CIDRAP report on the MMWR. The continued misinformation on these USDA sequences by the CDC and CIDRAP creates confusion on the early cases with “swine exposure”, which have no real linkage to symptomatic swine, or swine in states where human cases are found.
The only sources identified for the human H3N2v cases have been index cases in clusters in Minnesota, Iowa, and West Virginia, and the unprecedented detection of two clusters involving two distinct constellations of H3N2v, as well as a suspect H1N2v cluster for cases without swine exposure, continues to raise concerns that the acquisition of the H1N1pdm11 M gene in North American triple reassortants, including the recent H1N1v case in Wisconsin, are generating many human cases.
Moreover, there is also concern that limited testing and sequencing are grossly underestimating the number and diversity of novel influenza cases in the United States.
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