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Commentary

CDC Requests 24 Hour Notice of Suspect H3N2v Cases
Recombinomics Commentary 12:00
December 26, 2011

This document provides updated interim guidance for state and local health departments conducting investigations of infections with influenza A (H3N2) variant [(H3N2)v] viruses. The following case definitions are for the purpose of investigations of suspected, probable, and confirmed cases of influenza A (H3N2)v virus infection. CDC is requesting notification of all suspected and probable cases of influenza A (H3N2)v virus infection within 24 hours of identification. When possible, state health departments are encouraged to investigate suspected cases of influenza A (H3N2)v virus infection further to determine case status.

The above comments are from a newly released CDC document that provides case definitions for patients suspected to be infected by H3N2v (trH3N2 or H3N2pdm11).  The document was one of many released by the CDC in associated with the December 23, 2011 early release MMWR on H3N2v transmission and guidelines, which included a description of the latest cluster from West Virginia involving two epidemiologically linked cases represented by samples (A/West Virginia/06/2011 and A/West Virginia/07/2011) collected 16 days apart and linked through additional symptomatic children at a common daycare center in Mineral County.  This cluster was similar to recently described cases linked to a day care center in Iowa, involving an index case (A/Iowa/07/2011) and two classmates (A/Iowa/08/2011 and A/Iowa/09/2011) and symptomatic relatives (brother and father) of the index case.

The human transmission in these two clusters is fully supported by the sequence analysis of the confirmed cases.  The complete sequences from the two classmates in Iowa match all 8 gene segments of the index case or differ by 1 nucleotide for each gene segment.  Similarly, the partial Ha and NA sequences from the second case in West Virginia match the index case.  None of these confirmed or suspect cases have a linkage to swine.

Thus, these clusters have much in common with the first two confirmed cases in the 2009 pandemic, which involved two children who lived in separate counties in southern California, has no link to swine of each other, and were associated with symptomatic but untested contacts.

However, the 2011 clusters represent two distinct, but closely related constellations of genes which match in all gene segments except the N2 gene in the West Virginia cases, which also links to seasonal H3N2 sequences from 2003, but has evolved into a distinct lineage in swine, which is concentrated in trH3N2 cases, in contrast to the first 10 human cases, which have an N2 concentrated in trH1N2 swine.

Moreover, like the 2009 pandemic, the sequences in there twelve H3N2v cases in 2011 are not found in any swine isolates collected prior to the human spread seen in July and August cases in Indiana and Pennsylvania.

The case definition and request for 24 hour notification are designed to gather additional data on sustained transmission of H3N2v.  However, failures of the CDC PCR test to correctly diagnose H3n2v cases raises concerns that the samples identified in the CDC case definitions will represent a small subset of actual cases.

The PCR testing requires serious sequencing by the CDC, and the absence of such sequencing in prior cases continues to raise pandemic concerns.

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