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Commentary Sustained
trH3N2 Transmission In West Virginia 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. "It's not clear yet that these viruses have acquired the ability to circulate in humans in a sustained way. We certainly haven't seen that in the outbreaks that we've investigated" Bresee said. The above comments (in blue) describe the trH3N2 cluster at a Mineral County daycare center in West Virginia, followed by a CDC quote (in red) claiming that sustained transmission was not seen in investigated cases, which is clearly not supported by the above description, or the sequences from the two cases described above (A/West Virginia/06/2011 and A/West Virginia/07/2011). The sequences from the index case (1F) were similar to the first ten trH3N2 cases in 2011 (H3N2pdm11), except it had an N2 sequence that had been circulating in trH3N2 swine (in contrast to the first ten cases, which had an N2 that had been circulating in trH1N2 swine, although both N2 lineages traced back to seasonal H3N2 from 2003). Although only a partial sequence was obtained from the second case (3M), the N2 sequence matched the index case (758/760 positions were identical and the next closest sequence at GISAID had 16 differences). Similarly, the HA sequence was identical (230/230 position and was the only identical sequence at GISAID). Thus, although the index case developed symptoms on November 12, the second confirmed case did not develop symptoms until November 29, and the same trH3N2 was identified in a sample collected on December 7, indicating the virus was maintained at the day care center for almost a month, and many of the other symptomatic cases were likely infected by the same trH3N2. Moreover, neither confirmed case had a swine exposure, and the origin of the trH3N2 in the index case is unknown, but was likely another human, since this trH3N2 has not been reported in any swine sequence, in spite of the USDA surveillance program, which has released sequences from 150 swine isolates generated between 2009 and the first six months of 2011. Thus, the claim that the ability to circulate in a sustained manner in humans in CDC investigated cases is false, and the number of confirmed cases has been largely limited by a PCR test that fails to conclusively detect these trH3N2 cases, as noted above, as well as descriptions of most of the 2011 trH3N2 cases. Since the second cases did not seek medical treatment, most cases are not detected. However, the detection of the same constellation and lineages for the first 10 trH3N2 cases in 2011 indicates this novel H3N2pdm11 is widespread in humans, and has only been reported in one swine isolate, A/swine/NY/A01104005/2011, which was collected after the initial human cases in July and August, and was not from any of the states (Indiana, Pennsylvania, Maine, Iowa, West Virginia) reporting human trH3N2 cases. Moreover, the five most recent confirmed trH3N2 cases (in Iowa and West Virginia) as well as symptomatic contacts, had not reported recent swine exposure and the only confirmed sources for confirmed cases were in index case or symptomatic contacts in each outbreak. This clusters have led to the latest early release MMWR, and the “no evidence of” comments on sustained transmission are not supported by the sequences or epidemiology associated with the confirmed and suspect cases. Recombinomics
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