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H1N1v H1N2v H3N2v Cases Dominate US Influenza Sequences
Recombinomics Commentary 13:30
December 28, 2011

But Netherda stressed that there is no cause for alarm. The 12 cases reported since July is in stark contrast to the spread of H1N1. It was first discovered in mid-April 2009, near the beginning of the Southern Hemisphere flu season. Just two weeks later, swine flu had reached Sonoma County.

“Right now this is looking like it’s benign,” he said. “It’s just not taking off the way H1N1 did.”

The above comments compare H3N2v cases (H3N2pdm11 and trH3N2) to the 2009 pandemic (H1N1pdm09). However, the diversity of novel (variant) cases is markedly higher than 2009, and testing has been minimal.  Most of the novel cases have been negative or tested as inconclusive, unsubtypable, or seasonal H3N2, and confirmation has required testing by the CDC.  These circumstances have led to extremely limited results, which has been dominated by novel cases.  All 8 influenza A sequences from children under the age of 10 collected since the week 41 collection of the first Maine case on October 10 have been novel.  However, novel cases have dominated sequences for all age groups since early October as seen in the chronological list below.

There have been 16 influenza sequences beginning with the Maine Oct 10 collection date, and 10 have been novel (8 H3N2V, 1 H1N2v, 1 H1N1v), including two distinct constellations for the H3N2v cases (6 H3N2pdm11 and 2 trH3N2).  In this time from there were only 4 seasonal H3N2 sequences and 2 from H1N1pdm09 cases.

The number of sequenced cases has been limited in part by samples with low RNA levels, which has contributed to the lack of accurate results from the PCR testing, which is now dominated by the recently approved CDC PCR test, which is used by state labs.  However, the novel cases are identified through cross reactivity, which can limit sensitivity or create a mis-diagnosis of seasonal H3N2.

Thus, the true extent of diversity of novel cases is far from clear.  In the initial early release MMWR on the novel cases, the CDC requested samples from cases with swine exposure, and swine exposure was also mentioned in the MMWR on the Iowa cluster, which did not involve swine exposure.  The latest MMWR on H3N2 transmisison and guidance requests samples from suspect cases, and a number of new documents on novel cases (now called variant), although most emphasis has been on H3N2v cases, which are most common in recent sequences.

However, the recent identification of H1N1v (trH1N1) and H1N2v (trH1N2) as seen in the list below, raises concerns that the novel human cases are extremely unstable, and the lack of swine linkage to the recent H3N2pdm11, trH3N2, and trH1N2 cases (along with an absence of detail on the trH1N1 case) requires a dramatic increase in sample collection and sequencing, as was done for the 2009 pandemic.

Name Lineage Collection Date Age Gender (novel in bold)

A/West Virginia/07/2011    trH3N2           12/07    3F
A/Wisconsin/28/2011         trH1N1           12/01 55M
A/West Virginia/06/2011    trH3N2           11/21   1M
A/Iowa/09/2011                    H3N2pdm11 11/14   2M
A/Iowa/08/2011                    H3N2pdm11 11/14   1M
A/Iowa/07/2011                    H3N2pdm11 11/14    3F
A/Wisconsin/27/2011         H3N2              11/05 38F
A/Minnesota/19/2011         trH1N2            11/04   1F
A/Nevada/11/2011               H3N2              11/04      F
A/Florida/27/2011                H1N1pdm09  10/30  10F
A/Maine/07/2011                 H3N2pdm11  10/24   8M
A/Colorado/07/2011            H3N2               10/23  49F
A/Indiana/10/2011              H3N2pdm11   10/22  59M
A/Texas/12/2011                  H3N2               10/16  29M
A/Wisconsin/26/2011          H1N1pdm09  10/16      M
A/Maine/06/2011                 H3N2pdm11  10/10   8M
A/Oregon/06/2011               H3N2               10/04  76F
A/Oregon/07/2011               H3N2               10/03  69F
A/Indiana/09/2011               H3N2                10/03   1M
A/Minnesota/18/2011          H3N2                10/02  26F
A/Michigan/07/2011            H3N2                10/02  38F
A/New York/14/2011            H3N2               10/02  72

A/Pennsylvania/14/2011      H1N1pdm09    09/26 48M
A/Pennsylvania/13/2011      H3N2                09/23  56F
A/South Dakota/03/2011     H3N2                09/23 43M
A/Alaska/17/2011                 H3N2                09/16 56M
A/California/24/2011            H1N1pdm09    09/15 72M
A/Washington/17/2011        H3N2                 09/14 10F
A/Hawaii/05/2011                 H1N1pdm09    09/07 32M
A/Pennsylvania/10/2011   H3N2pdm11    08/26    9F
A/Florida/24/2011                H3N2                 08/25   1M
A/Louisiana/05/2011           H3N2                 08/25 73F
A/Pennsylvania/11/2011   H3N2pdm11    08/25    9F
A/Florida/22/2011                H3N2                 08/24  52F
A/Florida/25/2011                H3N2                 08/22     M
A/Pennsylvania/09/2011   H3N2pdm11     08/20    2F
A/Michigan/06/2011             H3N2                 08/18  36F
A/Hawaii/04/2011                 H3N2                 08/18  80F
A/Louisiana/06/2011            H3N2                 08/16 13F
A/Florida/21/2011                 H3N2                 08/15    M
A/Iowa/06/2011                     H3N2                  08/13 90F
A/Pennsylvania/12/2011      H3N2                  08/11 63M
A/Florida/20/2011                 H3N2                  08/04   8M
A/California/23/2011             H3N2                  07/31 63M
A/Indiana/08/2011                H3N2pdm11      07/27  2M

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