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Commentary
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Sequences from Swine H3N2 Cases Raise Concerns
Recombinomics
Commentary 22:35
November 12, 2010
The above comments describe reported swine flu human cases in the United States since 2005 (excluding pandemic H1N1 cases). Prior to mid-2009, all cases were H1N1. However, since mid-2009 there have been five H3N2 cases, and four of the five have been reported in 2010. These cases have similar internal genes, and have various combinations of H and N genes. For H3N2, all H and N sequences are human. For H1 the H and N genes can be human or swine.
The rise in H3N2 swine flu cases after the start of the 2009 H1N1 swine flu pandemic raises concerns that the widespread pH1N1 has led to alterations in internal genes, which have led to an increased frequency of human cases. An increased frequency in human H1N1 cases preceded the 2009 pandemic. Thus, the increase in H3N2 has led to concerns that pandemic H3N2 swine flu may follow. pH1N1 has jumped back to swine and is transmitting swine to swine, creating opportunity for genetic exchanges as seen in recent sequences from Thailand.
However, the monitoring of such changes is limited by the lack of public sequences from the human cases in the US. A full set of sequences from the Kansas case (22M) described above has been released, but sequences the four cases reported in 2010, including the 2009 case in Iowa, have not been released.
The dramatic rise in reported H3N2 swine flu in the US dictates more aggressive surveillance and transparency. The latest CDC comments cite differences between sequences from the two most recent cases, but such differences may be linked to diversity generated in the human population. Although the Pennsylvania case was in an area with swine, there was no documented exposure in the period preceding symptoms. Similarly, the case in Iowa in 2009 also did not have a clear swine link. Moreover, the Wisconsin case was a 7 month old baby, so direct contact with swine is also unclear.
Thus, there may be significant spread of swine H3N2 in humans that is largely missed by current surveillance. All of the swine H3N2 isolates have human H and N. For the Kansas sequence, A/Kansas/13/2009, the H sequence is related to human sequences from the 1990’s (see list here). The N sequence is related to human H1N2 sequences from 2003 (see list here).
Consequently, the detection of these swine infections is linked to sequencing. Unlike pandemic H1N1 which has swine H and N, the human H and N in swine H3N2 will be detected by human sub-typing tests, so detecting such sequences is a challenge. Consequently, there may be sequence diversity in swine influenza circulating in humans, and demonstrations of such associates may require phylogenetic analysis, which requires full sequences from the infections reported in 2010.
Therefore the sequence generated by the CDC for these cases, like the sequences for the Kansas case, should be released.
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