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Commentary
Repeated 2012
Media Myth On H3N2v Transmission
Recombinomics
Commentary 15:20
July 27, 2012
The above comment from a Helen Branswell piece on the H3N2v cluster at the LaPorte County fair in Indiana again suggests the earlier 2011 and 2012 cases which involved patients with swine “exposure” involved jumps from swine to humans. However, evidence (epidemiological and sequence) continues to point away from such jumps for most or all of the cases prior to the current cluster in Indiana.
The LaPorte cluster has the ingredients expected for H3N2v transition from swine to human contacts. The first expected factor is symptomatic swine. Media reports indicated 41 LaPorte swine were disqualified on July 13 because of fever. Moreover, additional swine had been voluntarily withdrawn by presenters because of swine flu symptoms. 12 of the swine (symptomatic and asymptomatic) were tested, all twelve were H3N2v positive. Moreover, sequence data indicated the swine isolates were closely related to each other, as well as sequences from H3N2v positive presenters and contacts (the CDC has released clone sequences from 2 of the cases and the sequences were identical in all eight geen segments).
Moreover, in addition to symptoms in the swine, a large number of human contacts were also symptomatic. H3N2v was confirmed in 4 cases, representing the largest confirmed H3N2v cluster reported to date, but media reports suggested significantly more attendees were infected. Media reports indicated 3 children and 1 adult represented the four confirmed cases, but media reports cited two symptomatic children in one family and three in another, signaling epidemiological linkage. Moreover the number of symptomatic children was said to exceed a dozen, which suggested most or all were H3N2v infected, since flu-like symptoms are unusual in Indiana in July.
The key elements cited above were absent from the earlier cases associated with swine exposure. The prior largest confirmed H3N2v cluster from a fair was the three cases at the Washington County fair in Pennsylvania, but none of the swine at the fair were symptomatic and none tested positive for influenza. Moreover, the three confirmed cases were not epidemiologically linked, and the sequenc e from the index case was distinct from the two subsequent cases. Similarly, the two cases associated with the Freyberg fair in Maine were not epidemiologically linked, although the sequences were virtually identical. The two cases developed symptoms more than 10 days apart and the second case developed symptoms more than 10 days after the end of the fair. Moreover, the symptomatic swine at the fair tested negative for influenza. The other two confirmed cases with swine exposure were linked to asymptomatic swine (in Indiana and Utah) and no swine positive for influenza A were identified.
In addition to the absence of linkage to symptomatic swine or swine positive for influenza A, swine surveillance also cast doubt on the role of swine to human jumps in the above cases. A recent study in Journal of Virology identified 674 MP sequences from collections between 2009 and 2011, which also were linked to HA and NA sequences from most of these isolates. However, this surveillance only identified one swine match (the previously described isolate from New York, A/swine/NY/A01104005/2011) with the 2011 and 2012 H3N2v cases.
More recent sequences initially identified four additional matches (from Iowa and Illinois), but all four were collected after the New York case, which was after the initial human cases from Indiana and Pennsylvania. Recently released sequences increased matches to 24, including three Iowa isolates collected prior to the New York isolate. However, none of these isolates were from samples collected prior to the human case in Indiana (in late July, 2011).
Moreover, the constellation in the human cases changed in the West Virginia cluster, swapping an N2 from swine H3N2 for the N2 from swine H1N2. Once again, the human constellation preceded the swine. The West Virginia constellation was also found in the first case in 2012 (Utah) and today the CDC released one full set of sequences from one of the LaPorte cases, which also matched the WV and UT cases. The first swine match for this constellation was in the February 2012 isolate from North Carolina, and the second match was from a May 5 collection in Indiana. However, the other 13 matches in swine collections since the West Virginia cases have been matches with the earlier human cases, creating more discordance between sequences found in swine and those in humans, decreasing the likelihood that swine to human jumps are driving the increase in human cases.
The latest CDC reports (MMWR and Have You Heard) on the LaPorte cluster suggest the 12 swine sequences will match the CDC sequence released today, increasing swine matches for this constellation to 14 (all from 2012 collections) and the number of human sequences to 7, representing cases in West Virginia, Utah, and Indiana, raising concerns that swine to human jumps may become more common based on the high attack rate of this constellation for swine and humans at the LaPorte County Fair.
Thus, there is little support for swine to human jumps in the prior cases with swine “exposure” but the LaPorte cluster may signal a significant increase in the detection of human cases with this novel constellation.
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