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Human trH3N2 Testing
• The patient was seen by a local health care provider on October 24, 2011, where a respiratory specimen was collected and forwarded to the Maine Health and Environmental Testing Laboratory.
• On October 28, 2011, diagnostic testing at the state laboratory was weakly positive for influenza A (H3), but negative for swine-origin influenza targets. The specimen was forwarded to CDC.
• On October 30, 2011, partial genome sequencing confirmed the virus as a swine-origin triple reassortant influenza A (H3N2) virus with the M gene from pH1N1.
• The patient reported multiple instances of close contact with pigs where sick pigs were present.
The above comments from the Louisiana Department of Health and Hospitals describing the second trH3N2 case from Maine, illustrates technical issues associated with the detection of trH3N2, and the role of swine exposure in testing procedures and agencies.
The initial forwarding of the sample by the local health care provider may have been facilitated by the prior swine exposure. The Maine testing lab used the newly approved CDC PCR test, which gave a clear signal for the first case from Maine, which was negative for pdm H1, but positive for pdm NP, strongly suggesting a trH3N2 infection, which was confirmed by CDC sequencing..
However, in the above case the RNA levels were low, so the two swine tetsts (H1 and NP) were negative, and the patient would have likely been characterized as seasonal H3N2 if there was no swine exposure. The patient had attended the Fryeburg fair, where symptomatic pigs had been noted, which were also links for the first confirmed trH3N2 case in Maine. The above case also participated in a pig scramble, which was an additional swine exposure, and the case also had exposures after the fair, which led to the further testing at the CDC where trH3N2 was identified by sequencing.
However, there is little evidence supporting a swine origin for the trH3N2 infection. The fair and associated pig scramble were on or before October 9, when the fair ended. Moreover, initial testing of the symptomatic swine were negative for SOIV and the swine involved in post fair exposures were asymptomatic, minimizing the role of these swine exposures in the infection with a case which had a disease onset date on October 22.
Similarly, the first cases was identified because of the PCR test which did return a pdm NP positive, leading to additional testing by the CDC, However, no SOIV’s have been identified in the symptomatic swine linked to the fair.
The absence of symptomatic swine linkages extends to the cases in Pennsylvania and Indiana, indicating the swine exposure was more important for testing than as a source of the infection. The veterinarian in Indiana was also identified as a suspect trH3N2 by the new PCR test, but the Indiana Board of Animal Health (BOAH) failed to identify symptomatic pigs linked to the veterinarian.
The first case in Indiana was also positive for H3 and would have been classified as seasonal H3N2 without the additional testing by the CDC, which was likely driven by the perceived swine exposure. However, the child had no direct contact with swine and his caretaker had contact with swine in the weeks preceding contact with the case, but the caretaker, her family, and the associated swine were all asymptomatic.
The first Pennsylvania case was influenza A positive, and it is not clear that there would have been further testing without the visit to the Washington County fair. The second case was tested because she was an exhibitor at the fair, while testing of the third case was driven by visits to the fair and a friend who was also an exhibitor at the fair. Thus, the swine exposure for all three cases linked to the fair drove the testing even though no symptomatic swine have been reported, and the sequences from the initial Pennsylvania case was distinct from the trH3N2 isolates by the two subsequent cases.
Moreover, enhanced US test has failed to identify the novel trH3N2 constellation in any swine in the US, which is also true for recent trH3N2 isolates from swine in Hong Kong.
Thus, there is still no link between the seven 2011 trH3N2 cases and symptomatic swine positive for any SOIV (and positive swine would also have to be trH3N2 infected with the constellation found in all seven human cases to be a credible source of infection). However, the CDC focus is on swine exposure, including requests for samples, leading to a lack of sub-typing of influenza A positives samples as seen in week 43 and 44 FluView as well as 31/32 samples from Region 4.
Therefore, swine exposure remains important for testing / detection of trH3N2, but not for transmission of the trH3N2 human contagion.