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CDC H3N2v Testing Bias Raises Pandemic Concerns
Recombinomics Commentary 11:15
August 14, 2012

H3N2v virus infection cannot be distinguished by clinical features from seasonal influenza A or B virus infection, or from infection with other respiratory viruses that can cause influenza-like illness (fever and either cough or sore throat). Therefore, the key to suspecting H3N2v virus infection in an ill patient at this time is to elicit an epidemiological link to recent swine exposure in the week prior to illness onset:

Direct contact (raising pigs, feeding pigs, cleaning pig waste) or indirect exposure to pigs – visiting a pig farm, walking through a swine barn at a county fair, etc.), especially if pigs were known to be ill; or

Close contact (within 2 meters or approximately 6 feet) to an ill person who had recent swine exposure.

A patient with influenza-like illness and an epidemiological link to recent swine exposure should be considered a probable H3N2v case.

The above comments are from the CDC’s instruction to physicians regarding human H3N2v cases.  This document will increase the heavy bias in H3N2v testing, which is largely limited to cases with direct or indirect swine exposure.  The instructions are similar to those announced after earlier detection of H3n2v cases, but the large number of cases identified in Indiana and Ohio will be more widely noted.

However, the sequences from the confirmed H3N2v cases in Indiana and Ohio are distinct from the first 10 H3N2v cases identified in 2011, due to the replacemnet of the NA gene, which had an H1N2 swine lineage, with an NA which has circulated in H3N2 swine.

This change (
A/West Virginia/06/2011 and A/West Virginia/07/2011) was initially detected in a large cluster in West Virginia, which did not have swine contact or exposure.  The outbreak led to a series of CDC announcements, but the H3N2v was not detected during the height of the 2011-2012 flu season.

However, in late March H3N2v was identified in Utah, and the NA sequence matched the West Virginia sub-clade.  Although this sub-clade was rarely detected in swine, and not detected in any swine samples collected prior to the outbreak in West Virginia, it was also detected in the July isolates in Hawaii, Indiana, and Ohio, signaling human adaptation and spread.

This H3N2v could also infect swine, so the July fairs did lead to H3N2v infections in swine, based on CDC descriptions of the outbreaks, although sequences from the July swine isolates have not been released.  The most recent H3n2v swine isolates were from Ohio, but all four isolates matched the 2011 human cases and were easily distinguished from the cases in West Virginia as well as the 2012 human isolates.

Thus, the sequence data supports a sub-clade that has adapted to humans, but all 2012 isolate have direct or indirect linkage to swine, which is due to the heavy testing bias.

Seasonal influenza is rare in the summer in the United States, and cases are likely to be due to H3N2v, especially in younger patients.  However, the CDC has not acknowledged the NA sequence differences between the the 2012 and 2011 human cases, or the size of the cluster in West Virginia.

Moreover, the biased testing largely limits H3N2v cases to those with direct or indirect swine contact, which is followed by claims of a lack of community spread.

This biased sampling and testing remains hazardous to the world’s health.

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