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Evolution of the 2011 Swine trH3N2 Pandemic
In the spring of 2009 another trH1N1 was isolated from humans. This trH1N1 was distinct from the various trH1N1’s isolated in the United States prior to the 2009 pandemic. Although the originating swine were not identified prior to the start of the pandemic, pandemic H1N1 infections in swine were reported worldwide, as human spread the virus and subsequently infected swine.
This dramatic expansion of pandemic H1N1 was followed by the first trH3N2 case in the United States in late July, 2009 at another county fair, in Riley, Kansas site of the start of the 1918 pandemic in the United States. The infection, A/Kansas/13/2009, was important because the internal genes were related to the trH1N1 that caused the Huron County Fair outbreak. The Kansas case was quickly followed by a case in Iowa, A/Iowa/16/2009 and a case in Minnesota in the spring of 2010, A/Minnesota/09/2010, which were also trH3N2.
Activity increase in November of 2010, when WHO issued a pager alert describing two trH3N2 infections, one in Illinois (which was subsequently reported by Wisconsin as A/Wisconsin/12/2010) and one in Pennsylvania (A/Pennsylvania/14/2010). The pager alert created significant concern in eastern Europe, which was blunted by a CDC claim that the trH3N2 did not easily transmit because the Wisconsin and Pennsylvania cases were 6 weeks apart and differences indicated the two virions did not come from a common source. However, at the time there was a second Pennsylvania case, A/Pennsylvania/40/2010, that was under investigation.
The CDC released sequences from the earlier cases, and most genes were closely related to each other, as well as the internal genes from the 2007 Huron Fair isolates. The data indicated the trH3N2 was transmitting in humans because there were more close human matches than swine matches, in spite of increased swine surveillance.
The pandemic concerns were increased when another Minnesota trH3N2 case, A/Minnesota/11/2010 was identified. It was closely related to the earlier case from Minnesota, A/Minnesota/09/2010, but was even closer to the Wisconsin case, indicating the later version was transmitting in humans. Concerns of human transmission were increased because of a ongoing analysis of contacts.
In early 2011 a second case in Pennsylvania, A/Pennsylvania/40/2010 was announced. It was the first confirmed trH3N2 case added in 2011, but was from a patient infected in September, 2010, with a disease onset date within a week of the Wisconsin case. Thus, when the pandemic alert was issued by WHO there were three trH3N2 cases under investigation, and the unreported case was virtually identical to the Wisconsin case. Thus, in September there were two trH3N2 cases in two states, WI and PA, and the sequences were virtually identical, even though the cases were not epidemiologically linked.
The second Pennsylvania case was followed by a third Minnesota case. The daughter of the November Minnesota case was serologically confirmed to have been trH3N2 infected in spite of no contact with swine. Moreover, additional family members had been symptomatic in November, defining a familial cluster composed of two lab confirmed trH3N2 cases and multiple suspect cases (testing of contacts was inconclusive).
This cluster announcement was followed by the selection of the isolate from the index case, A/Minnesota/11/2010, as a pandemic H3N2 vaccine target and the daughter of the index case was added to the list of confirmed trH3N2 cases. This raised the total listed for 2011 to two, even though both cases were infected in 2010.
That update was followed by the release of sequences from the recent case (1M) in Indiana, A/Indiana/08/2011, which had genes closely related to the cases in Minnesota, Wisconsin, and Pennsylvania. However, it had also acquired an M gene segment from pandemic H1N1. This constellation had never been reported previously, although the pandemic H1N1 M gene had been detected in swine with additional pandemic H1N1 gene segments. The acquisition of the pandemic H1N1 M gene segment increased pandemic concerns because the pandemic H1N1 M gene was critical for efficient airborne transmission.
The week 34 MMWR had two new trH3N2 cases, one from Indiana and one from Pennsylvania, raising the Pennsylvania total to three and marking the first report of two trH3N2 cases in the same week.
The CDC then put out an early MMWR on the two cases, noting that the Pennsylvania case had also acquired a pandemic H1N1 M gene, increasing concerns that this match signaled widespread transmission of trH3N2 with genes closely related to the human cases in Minnesota, Wisconsin, and Pennsylvania, but with a H1N1 M gene conferring efficient airborn transmission. The CDC requested nasopharyngeal swabs from patients with flu symptoms and swine contact, and the Pennsylvania Department of Health began collecting samples from symptomatic attendees of the Washington Country agricultural fair.
Over the weekend the CDC updated the underlying data in the serotype figure released on Friday (week 34). The table had added an unsubtypable isolate for week 33 and an H3N2 isolate for week 34. Neither of these cases was delineated in the figure published in the week 34 report. The FluView only publishes data on a tiny fraction of the actual flu cases in the United States. Thus, the one unbsubtypable case could represent hundreds or thousands of additional unsubtypable cases, which are likely to be trH3N2 cases (the last unsubtypable reported by the CDC was pandemic H1N1), which is also true for recent cases that sub-type as H3N2, since the H3 and N2 are from the human lineage, but modified through evolution in swine since the early 1990’s.
More detail on the week 33 unsubtypable (unable to sub-type) case added this weekend, and release of the sequences from the recent Pennsylvania case, would be useful.