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Vague trH3N2 CDC Case Reporting Raises Concerns
Recombinomics Commentary 22:00
November 14, 2011

Two human infections with novel influenza A viruses were detected in individuals from two states (Indiana and Maine). Both patients were infected with swine-origin influenza A (H3N2) viruses. One patient was hospitalized, but has now been discharged and both continue to recover from their illnesses. Both patients reported close contacts with pigs preceding their illness onset.

The above comments are from the CDC’s week 43 FluView which came out almost exactly one year after the WHO pager alert on two trH3N2 cases in Illinois and Pennsylvania.  These two cases created considerable concern in eastern Europe, which was answered by the CDC, who claimed no human to human transmission, based in part on the sequence differences between the two isolates, as well as the 6 weeks between disease onset dates.  More detail was provided in the first “Have You Heard?” on trH3N2, which is used for background and detail for the news media.  These reports have specifics on disease onset dates and some data on exposure.

The two current cases are significantly more alarming than the cases described a year.  The 2011 cases (A/Indiana/10/2011 and A/Maine/07/2011) developed symptoms two days apart and two weeks after another case in Maine, A/Maine/06/2011).  The sequences from the two Maine cases were virtually identical, and the Indiana case had the same constellation of genes, some of which were closely related to the two sequences from Maine, while others were more closely related to the four July / August cases from Indiana (A/Indiana/08/2011 and Pennsylvania (A/Pennsylvania/09/2011, A/Pennsylvania/10/2011, A/Pennsylvania/11/2011).  However, all seven isolates had the same overall constellation of genes which evolved from the 2010 sequences and also acquired the M gene from H1N1pdm09, and this constellation has never been reported in swine.

Although the CDC now cites no sustained human transmission, human to human transmission has been acknowledged for the cluster in Minnesota, as well as the first 2011 case (2M, A/Indiana/08/2011).  However, the absence of sustained transmission is based on negative data generated by the same investigators and procedures that have failed to identify a source for any of the 2011 cases.  Thus, without knowledge of how the confirmed cases were infected, there is no data on other cases infected by the same source(s).

Moreover, there is little data supporting infection from a swine “exposure”.  The first case in Maine was from Cumberland County and was said to have had swine exposure from attendance at an agricultural fair in the week prior to symptoms on October 7.  This description matches the Cumberland County fair, which ended October 1.  However, the incubation period for influenza is short, generally two days with a range of 1-4 days.  Thus, the 6-7 day gap between the swine exposure and onset of symptoms is outside of the traditional incubation period.
This time gap is a greater issue for the Maine case described in the week 43 FluView because the Maine CDC indicated the swine exposure for the second case was also an agricultural fair, and media reports indicated the Maine cases lived in the same area, suggesting the swine exposure for the second case was also the Cumberland County fair, which ended three weeks prior to symptoms.  One of the cases participated in a swine scramble (see video of the Oct 1 pig scramble).

Moreover, swine “exposures” for the earlier 2011 cases have no reports of symptomatic swine.  Media reports indicated the swine at the Washington County fair were asymptomatic, and the early release MMWR indicated the caretaker for the first case in 2011 was asymptomatic, as were associated swine.

The two cases above did lead to an Taiwan CDC alert for travel in the United States.  They cited the CDC report to WHO, which indicated that the most recent Indiana case was a veterinarian who was hospitalized for three days.  This case was investigated by the Indiana State Board of Animal health, who noted that all swine visited by the veterinarian had been asymptomatic for at least a month.

Thus, there are no reports of any of the seven 2011 cases being exposed to symptomatic swine in the week prior to disease onset, and no swine with a constellation of gene matching the seven cases have been reported.

Thus, the lack of detail in the CDC week 43 FluView raises concerns that such detail excludes the swine as a reasonable source of the trH3N2, as does the lack of testing of influenza A positive cases without swine exposure as seen in the week 44 report or region 4 data on the entire 2011/2012 season.

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