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Human Clonal Expansion of July/August 2012 H3N2v
Recombinomics Commentary 14:15
August 31, 2012

Today, 52 additional cases of H3N2v are being reported, bringing the total number of such infections since July 2012 in the United States to 276 across 10 states. Investigations into H3N2v cases indicate that the main risk factor for infection is exposure to pigs, mostly in fair settings; however, CDC also is reporting three instances of likely human-to-human spread of this virus during the current outbreaks.

According to CDC’s Dr. Joseph Bresee “limited human-to-human spread of this virus has been seen in the past, but the H3N2v virus has not previously -- and is not now -- spreading easily from person-to-person.” According to Bresee, “Most cases are occurring in children who are exhibiting pigs, or helping to exhibit pigs and have occurred after a lot of very close contact with pigs over a relatively long period of time.”

The above comments from the August 24, 2012 CDC update on H3N2v is not supported by the data.  The Gallia Junior County Fair outbreak involved hundreds of attendees with influenza like illness (ILI) and 20% of the cases were adults.  A rapid test on 200 of the ILI cases yielded 69 influenza A positives, indicating virtually all were infected with influenza, and further testing of a subset confirmed H3N2v in 11 of the initial cases, indicating the H3N2v is spreading easily from person-to-person.

However, the sequence data is more compelling than the epidemiological data, which is compromised by the heavily biased sample selection.  Three examples of human to human (H2H) are cited above, but epidemiological studies are limited because the initial cases had swine exposure.  Testing of H3 positive cases in those without swine exposure are largely limited to the CDC RT-PCR testing at state labs, and have not been confirmed by sequence data.  In the week 33 CDC FluView, the table on underlying data for the serotype figure included a column for H3N2v cases, which showed that the rise in these cases correlated with arise in seasonal H3N2, raising concerns that many of the H3N2 cases without swine exposure are being reported as seasonal H3N2 and have not been sequence confirmed.  This concern is highest for cluster of H3N2 in children under the age of five, as was seen in the 6 cases reported in the Ashland-Boyd County press release for clusters in Kentucky.  Seasonal H3 was also reported in association with confirmed H3N2v cases in West Virginia.

In contrast to the testing limitations, the sequence data provides hard data for a clonal expansion of a novel sub-clade first reported at a day care center in West Virginia in later 2011.  The two sequences,
A/West Virginia/06/2011 and A/West Virginia/07/2011, matched the 10 prior 2011 cases in 7 of the 8 gene segments.  However, the NA sequences matched swine H3N2 sequences, in contrast to the early human sequences, which match swine H1N2.  This novel sub-clade has seen in all 35 2012 H3N2v sequences released by the CDC, and the 34 sequences from July and August collection represent clonal expansion across the country.

Twenty of the sequences were from multiple locations in Indiana (see list below). While nine were from multiple locations in Ohio.  One sequence was also released from Hawaii, Maryland, Minnesota, Pennsylvania, and Wisconsin.  These sequences were remarkably similar, even though they were collected between July 12 and August 16 over a wide geographical area.  Phylogenetic analysis placed the West Virginia sequences at the base of branches generated for 7 of the 8 gene segments.  The NP sequences were rooted in closely related sequences from the sub-clade present in the first ten 2011 human sequences, although the West Virginia sequence was also on this branch.

This clonal expansion is not supported by the USDA enhanced surveillance of swine.  Only two swine isolates, A/swine/North Carolina/A01203272/2012 (collected February 13) and A/swine/Indiana/A01203509/2012 (collected May 9) match (in HA, NA, MP sequences) the clonally expanded human sequences.  In contrast, 26 matches (based on HA, NA, MP sequences) were found for the 2011 human sequences, including recent sequences in Ohio and Indiana, yet none produced a matching human sequence in 2012 and the last match was the Iowa cluster in November, 2011, which had no swine exposure. 

Thus, the H3N2v sequence data does not support the widespread presence of the novel sub-clade in swine, or frequent transmission of H3N2v from swine to humans.

Alphabetical list of July / August H3N2v Sequences

A/Hawaii/03/2012               July 12
A/Indiana/06/2012              July 16
A/Indiana/07/2012              July 16
A/Indiana/08/2012              July 16
A/Indiana/09/2012              July 16
A/Indiana/12/2012              July 27
A/Indiana/13/2012              July 28
A/Indiana/14/2012              July 30
A/Indiana/15/2012              July 29
A/Indiana/16/2012              July 31
A/Indiana/17/2012              July 30
A/Indiana/19/2012              July 29
A/Indiana/21/2012              July 31
A/Indiana/31/2012             August 1
A/Indiana/38/2012             August 1
A/Indiana/43/2012             August 1
A/Indiana/46/2012             August 1
A/Indiana/49/2012             August 1
A/Indiana/52/2012             August 1
A/Indiana/59/2012             August 2
A/Indiana/60/2012             August 2
A/Maryland/20/2012          August 16
A/Minnesota/112012         August 15
A/Ohio/13/2012                 July 27
A/Ohio/14/2012                 July 29
A/Ohio/15/2012                 July 28
A/Ohio/16/2012                 July 28
A/Ohio/17/2012                 July 28
A/Ohio/18/2012                 July 27
A/Ohio/20/2012                 July 28
A/Ohio/23/2012                 July 30
A/Ohio/24/2012                 August 2
A/Pennsylvania/13/2012  August 15
A/Wisconsin/22/2012       August 13

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