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CDC trH3N2 Testing Continues To Be An IHR Issue
Recombinomics Commentary 15:50
November 14, 2011

CDC is required to report all cases of human infection with novel influenza viruses – including swine influenza viruses -- to the World Health Organization (WHO) as part of the International Health Regulations (IHR). Domestically, CDC reports these cases in this report and on its website.

The above comments have been added to the week 43 FluView report on the two trH3N2 cases from Maine and Indiana, as well as the week 41 FluView report on the first case from Maine, as well as other CDC documents associated with the recent trH3N2 cases.  However, the IHR concerns were related to other cases under investigation of cases whose testing was incomplete, including influenza A positive cases such as the cases in the latest FluView (week 44), when none of the influenza A positive samples were sub-typed, or the 32 influenza A positive cases in Region 4, where only 1 has been sub-typed.

The reporting of the recent trH3N2 cases, especially those in late 2010 or those in 2011 have been reported at multiple sites, including CDC FluView, MMWR, and “Have You Heard” and the recent warning of travel in the United States put out by the Taiwan CDC cited the reporting of the two most recent cases at the WHO IHR password protected website, but then added the statement that there had been 15 trH3N2 cases in the United States since 2005, when all have been reported since August, 2009, after the start of the 2009 pandemic.  This same error was stated on the WHO update on pandemic vaccines, and these errors appear to have originated from CDC reports which did not distinguish between the date of the first H1 case in 2005, and the first H3 case in 2009.

These start dates are important in understanding the evolution and emergence of the novel version of trH3N2 found in all seven human cases in 2011, and no swine isolate anywhere.  The sequences released by the CDC in late 2010 of the prior H1 and H3 cases, as well as the release of the subsequent h3 cases shows clear clustering of human sequences in 2010, signaling adaptation to humans, and a 2011 novel constellation in all trH3N2 cases, signaling transmission.  One of the markers of clustering, E618D, in PB1 was in the first case in 2009, and all cases in 2010, and was in all H1N1pdm09 isolates, signaling acquisition by recombination.  In 2011 a new trH3N2 constellation emerged in the seven human cases, which acquired the M gene from H1N1pdm09 via reassortment.

The human transmission was signaled prior to the 2011 cases by the first case reported in 2011, which was from a case that was initially designated as a seasonal H3N2 case and reporting was delayed 5 months.  The sequence, A/Pennsylvania/40/2010, came out 6 weeks later and was virtually identical to the first case in the WHO pager alert, A/Wisconsin/12/2010, signaling human transmission.  The second case reported in 2011 was the daughter of the Minnesota index case, A/Minnesota/11/2010.  The lack of swine contact by the daughter signaled human transmission, which was confirmed serologically.
The H3 sequence of the 2011 cases is closely related to the four cases above, while the N2 sequence matches the other case in the pager alert, A/Pennsylvania/14,2010.  The evolution from the 2010 cases as well as the acquisition of the M gene from H1N1pdm09, demonstrates the emergence of a human contagion, and the importance of the correct date for the first trH3N2 case, as well as the clear sequence data.

However, in spite of the clear evidence for human transmission, the CDC has been focused on cases with a swine “exposure”, which is more important for CDC testing, than actual transmission of the contagion.  The first 2011 case had no swine exposure, and his caretaker, who had swine exposure had no symptoms, which is also true for the associated swine.  The same is true for the three Pennsylvania cases who attended the Washington County fair, but no symptomatic swine were identified at the fair.  Similarly, swine at the Cumberland County fair in Maine have not been reported as having flu symptoms, and disease onset dates for the two Maine cases discount the role of the swine at the fair.  Similarly, the Indiana State Board of Animal Health confirmed that the contact swine for the veterinarian were asymptomatic for a least a month prior to contact.

Thus, the IHR reporting issues are more focused on the CDC testing, or lack thereof, and not the reporting of the confirmed cases supported by the public sequences.  Similarly, the concern over cases under investigation, or untested, in spite of being influenza A positive, continues to be an IHR reporting issue. 

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