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Commentary
CDC H3N2v
Sub-Clade Secret Raises Pandemic Concerns
Recombinomics
Commentary 14:30
August 24, 2012
H3N2v is a new flu virus that is currently infecting both pigs and humans in the United States, including Pennsylvania. Although rare, the virus can spread from pigs to people and from people to pigs. This new virus is different from previous H3N2 human infections because it also contains part of the 2009 H1N1 virus. It is the same virus we saw in three ill people who had all attended the Washington County Fair last year in Pennsylvania.
The above description is from the Pennsylvania Department of Health Q&A page on H3N2v. Pennsylvania is currently reporting 31 H3N2v cases (6 confirmed and 25 probable) in at least three counties. However, the description of H3N2v uses a broad definition of the H3N2v with the H1N1pdm09 M gene, which first appeared in an Indiana case in July 2011 (A/Indiana/08/2011). This version was identified in the first 10 human cases in 2011, including the three at the Washington County Fair (A/Pennsylvania/10/2011, A/Pennsylvania/11/2011, A/Pennsylvania/12/2011). This sub-clade has subsequently been found in swine in many states, including four June, 2012 isolates in Ohio.
However, there have been no reported human cases involving this sub-clade since the November 2011 cluster in Iowa, which involved three confirmed cases (all attended the same day care center), A/Iowa/07/2011, A/Iowa/08/2011, A/Iowa/09/2011) and two suspect cases (untested but symptomatic father and brother of the index case). This cluster had no swine contact or exposure and the transmission at the day care center (as well as within the family) clearly demonstrated the ability of this sub-clade to transmit human to human (which was confirmed by virtually identical sequences in all three cases). However, in spite of widespread detection of this sub-clade in swine in 2012, none of the 2012 sequences released to date (from Utah, Hawaii, Indiana, and Ohio), match this earlier sub-clade, which destroys the CDC position that H3N2v frequently spreads from swine to human.
All of the human 2012 H3N2v sequences released to date match the sub-clade first detected at a Mineral County day care center in West Virginia (A/West Virginia/06/2011 and A/West Virginia/07/2011) where there was also no swine exposure or contact. The disease onset dates between the two confirmed cases was two weeks apart and the index cases was initially confirmed while hospitalized. Thus, the index case did not infect the classmate. Instead, that infection was due to human to human transmission at the day care center as indicated by an epidemiological investigation which initially identified ILI (influenza-like illness) in 23 of the 70 contacts of the index case.
The sub-clade in West Virginia was easily distinguished from the earlier cases because the N2 had been acquired via reassortment and represented a different linage one that had been evolving in H3N2 swine, instead of evolution in H1N2 swine, which was the lineage of the first 10 human cases. These two lineages are easily distinguished and can be classified within seconds of blast the full or partial N2 sequences. That BLAST approach well generate at match with the first 10 human H3N2v cases in 2011, or the 20 human H3N2v cases since the Iowa cluster (the last two sequences in 2011 and all 18 sequences from 2012.
Thus, swine sequences can be easily classified into the two sub-clades using the HA, NA, and MP sequences, which are represented in all sequences released by the USDA. A summary of the USDA data was posted on the CDC website, which cited 138 H3N2 sequences since October 1, 2011 (FY2012), which included 57 with an H1N1pdm09 M gene (which these CDC is now calling H3N2pM). USDA sequences at Genbank collected in FY2012 total 67, with 45 designated as H3N2pM. The 12 case difference between the public sequences, which go through June, and the USDA cases which go through the end of July, are the likely the 12 swine isolates from the LaPorte County Fair, where there have been at least 5 confirmed H3N2v cases and more than a dozen who were symptomatic and therefore would be classified as probable using the new CDC guidelines. Thus, it is likely that the 12 recent swine cases were due to human to swine transmission.
However, the 45 public H3N2pM sequences provide clear data on the USDA surveillance of US swine. These sequences represent all of the USDA data on H3N2pM isolates from collections through June, 2012. 19 of these sequences have an H3 lineage that matches the 2011/2012 human H3N2v cases, but only two match the recent lineage identified in humans. Thus, the CDC claim that the H3N2v in the 2012 cases has been detected by the USDA in many states is false. The N2 match for H3N2pM is limited to a February isolate from North Carolina and a May isolate from Indiana. The CDC statement is only accurate if the N2 differences are ignored.
Thus, the CDC and USDA sequence data thoroughly refutes the CDC position. The 2011 sub-clade is widespread in swine in 2012, but has produced no 2012 human cases, while the 2012 sub-clade is rare in swine but has produced all of the 2012 human cases (as well as the 2011 West Virginia cluster).
Therefore, for the CDC to maintain its frequent swine to human position, the sub-clade differences are kept secret, leading to misstatements such as the quoted statement by the Pennsylvania Department of Health claiming a match between the 2012 cases in Huntingdon County and the 2011 cases in Washington County.
The CDC sub-clade secret remains hazardous to the world’s health and hides the serious pandemic potential of the 2012 sub-clade, which has acquired NA N234D, which is in all of the cases from the Laporte and Butler County Fairs.
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