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Commentary
Patient Zero In
The 2011 H3N2v Pandemic
Recombinomics
Commentary 09:00
August 11, 2012
An investigation was conducted to ascertain respiratory illnesses among contacts of the child that occurred during November 9–December 19. Multiple contacts, including children who regularly attended day care with the child, were found to have had respiratory illness during this period. On November 29, a second child aged <5 years who attended day care regularly with the first child and who had no recent travel or swine exposure became ill with fever, cough, diarrhea, and rhinorrhea. The second child did not seek medical care and recovered fully from the illness. A respiratory specimen obtained from the second child on December 7 was inconclusive by rRT-PCR at the West Virginia Office of Laboratory Services; however, the specimen was confirmed as influenza A (H3N2)v with the M gene from the A(H1N1)pdm09 virus via genome sequencing at CDC.
...investigation of a case in West Virginia has identified a possible outbreak, with 23 out of 70 contacts of the case reporting ILI.....
The above comments from the December 23, 2011 CDC MMWR (in blue) and a December 15, 2011 alert from the California Department of Public Health (CDPH) (in red) describe this first two confirmed H3N2v cases with a novel constellation of genes, which replaced the NA gene that was in the first 10 H3N2v confirmed cases in 2011 (which had an H1N2 swine lineage) with an NA gene that had an H3N2 swine lineage. Although both N2 sequences traced back to seasonal H3N2 circulating in 2003, the circulation in swine had produced two readily distinguishable lineages. The other 7 gene segments, including the H1N1pdm09 MP gene matched in the two sub-clades.
The above CDC MMWR was an H3N2v update, which summarized prior H3N2v cases and offered testing guidelines. It followed an alert that had been sent to all fifty states noting the large cluster described in the above alert issued by the CDPH to county labs in California. Although the size of the cluster was described in the CDC report to states, the 23 cases of ILI linked to the index case (patient zero) was not conveyed to the public.
However, the MMWR did note that the day care cluster was in a group that did not have swine contact or exposure and the time gap between the two confirmed classmates supported human to human transmission at the day care center. Although the CDC alert to the fifty state labs did not lead to the detection of a confirmed H3N2v case during the peak of the 2011/2012 flu season, an H3N2v case was identified in late March in Utah. The sequence of the H3N2v from this case, A/Utah/10/2012, matched the novel sub-clade detected at the West Virginia daycare center.
Much larger numbers of H3N2v have been at state and county fairs, which are targeted by a CDC surveillance program that tests ILI cases with swine exposure. Sequences from cases in Hawaii, Indiana, and Ohio have been released (A/Hawaii/03.2012, A/Indiana/06/2012, A/Indiana/07/2012, A/Indiana/08/2012, A/Indiana/09/2012, A/Indiana/12/2012, A/Ohio/13/2012) from samples collected from a farmer in Maui, Hawaii, the first four confirmed cases at the LaPorte County Fair in Indiana, the first confirmed case at the Jackson County Fair in Indiana, and the first confirmed case at the Butler County Fair in Ohio.
All were closely related to each other and matched the novel H3N2v detected in at the West Virginia day care center. Therefore, the index case for that large outbreak has been designated patient zero for the 2011 H3N2v pandemic.
Although the 2012 H3N2v cases have been associated with swine exposure, the link is dependent on the CDC program targeting off season ILI cases with swine contact. Jackson County reported ILI in area residents for 6 weeks prior to the fair, but no testing was done until H3N2v was confirmed at the LaPorte County Fair and the Indiana State Department of Health sent out an alert, similar to the alert sent by the CDC on the targeting of cases with swine exposure.
This targeting has created the illusion that the novel H3N2v, which was first detected at the West Virginia day care center, is transmitting from swine to humans, which is not supported by the USDA swine surveillance program, which only detected two examples of the novel H3N2v in swine. The program identified 26 matches with the H3N2v detected in the initial human cases in 2011. However, the 2012 swine matches for this sub-clade did not lead to any confirmed human cases. The last confirmed human case was from the day care cluster in Iowa in November, 2011.
This discordance between swine and human cases with the two H3N2v sub-clades supports transmission of the novel sub-clade in humans, athough the highly biased testing by the CDC program targeting ILI with swine exposure has created an illusion of swine to human transmission.
Aggressive testing of ILI cases without swine exposure is long overdue.
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