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West Virginia Large and Extended trH3N2 Cluster
Recombinomics Commentary 23:15
December 23, 2011

On November 19, a child aged <5 years developed acute onset of fever after 1 week of cough and congestion. The child had been hospitalized for an unrelated condition 2 days before the onset of fever. On November 21, a respiratory specimen was collected. Rapid diagnostic tests conducted by the hospital were negative for influenza and respiratory syncytial virus, but influenza A was identified by an alternative rRT-PCR at the hospital. The specimen was forwarded to the West Virginia Office of Laboratory Services, where it was identified as a suspected influenza A (H3N2)v virus. Subsequent genome sequencing conducted at CDC confirmed the virus as A(H3N2)v with the M gene from the A(H1N1)pdm09 virus. The child, who had no recent travel or exposure to swine, was discharged on November 21, and has since recovered from the influenza illness.

An investigation was conducted to ascertain respiratory illnesses among contacts of the child that occurred during November 9–December 19. Multiple contacts, including children who regularly attended day care with the child, were found to have had respiratory illness during this period. On November 29, a second child aged <5 years who attended day care regularly with the first child and who had no recent travel or swine exposure became ill with fever, cough, diarrhea, and rhinorrhea. The second child did not seek medical care and recovered fully from the illness. A respiratory specimen obtained from the second child on December 7 was inconclusive by rRT-PCR at the West Virginia Office of Laboratory Services; however, the specimen was confirmed as influenza A (H3N2)v with the M gene from the A(H1N1)pdm09 virus via genome sequencing at CDC.

The above comments from the December 23, 2011 early release MMWR describe the West Viginia cluster represented by two cases (1M – A/West Virginia/06/2011 and 3M – A/West Virginia/07/2011).  As expected, this cluster is significantly larger than the two confirmed cases based on disease onset dates.  The first case had initial symptoms as early as November 12 and developed fever on November 19.  The second case developed fever 10 days later strongly suggesting that infection was due to other symptomatic children at the day care center.  Although only partial HA and NA sequences have been released from the second case, the N2 sequence was closely related to the index case, which was from a swine trH3N2 lineage and easily distinguished from the N2 in the first ten H3N2pdm11 cases in 2011.  Moreover the HA sequences from the two cases were identical, and both cases had a H1N1pdm09 M gene.

Thus, the sequences from the two isolates signal human to human transmission, involving additional common contacts.  Neither case had any swine exposure, and as was seen in the Iowa cluster, the epidemiological linkage for the latter cases are daycare children under the age of three.

Thus, both clusters involve trH3N2 which represent two distinct constellations.  The Iowa cluster matches the H3N2pdm11 found in 7 earlier cases in 2011 and the swine sequence from New York, while the West Virginia cluster involve a trH3N2 constellation which has not been reported in swine and matches the H3N2pdm11 lineages in 7 of the 8 gene segments.

The detection of two confirmed clusters involving two distinct novel trH3N2 lineages without swine exposure is without precedent.

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