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Commentary

CDC H3N2v Detection Failures Raise Pandemic Concerns
Recombinomics Commentary 13:45
April 21, 2012

On March 29 a child between the ages of 0-5 presented to a local ER with a high fever, sore throat, and intermittent headache.

Testing results suggested a variant influenza strain, which was confirmed today as swine-origin influenza A H3N2 by CDC.

The child had contact a week prior with swine at a family-owned slaughterhouse.

The above comments are from an April 9 post by the Canyon View Medical Group, with offices in Weber County, Utah.  The Canyon View post was two days prior to the press release by the Weber Morgan Health Department and 3 days prior to the initial announcement by the CDC, suggesting the Canyon View Medical Group had first-hand knowledge of this case.

The swine contact 7 days prior to disease onset, and the USDA comments on the absence of symptomatic swine at the facility, decrease the likelihood that the child was infected by swine contact.  The sequences, A/Utah/10/2012, from this case demonstrate a closely similarity with the sequences (A/West Virginia/06/2011 and A/West Virginia/07/2011) from the West Virginia H3N2v cluster linked to a Mineral count day care center, which included influenza like illness in 23 contacts of the index case, with the absence of swine exposure for the index case and symptomatic contacts.  Moreover, the sequences in the two tested cases were virtually identical and represented a novel constellation (the N2 gene was from a swine H3N2 lineage instead of the H1N2 lineage present in the first 10 human cases I 2011.  This novel constellation has never been reported in swine, but was present in the first human case of 2012.

The gap between the first case in 2012 (March 29) and the last case in 2011 (December 7) represents the pear of the flu season in the United States yet no H3N2v cases were identified.  This detection failure, in spite of a CDC alert issued during the investigation of the West Virginia cluster, and a plea for samples in a January, 2012 MMWR, highlights the limitations of the CDC PCR test, which is used by states laboratories in the United States and many countries, including those in Europe.  A recent report on H3N2v testing in Europe also cited a failure in the detection of H3N2v, again highlighting the limitations of this assay, which relies on cross reactivity with H3 seasonal flu coupled with NP H1N1pdm09.  Consequently, most samples are either negative or inconclusive or incorrectly identify the sample as seasonal H3N2.
Consequently, testing during the height of the flu seasonal fails to detect H3N2v, and limits detection to periods when seasonal H3N2 levels are low, suspicions are raised by a history of “swine exposure”, or RNA levels in the tested sample are high.

These detection failures highlight the need for CDC sequencing of samples from young children (under 5) with influenza like illness.

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