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Commentary
Swine
trH3N2 Phylogenetic Analysis Without Sequences
Recombinomics
Commentary 03:14
November 14, 2010
The above comments are from the CDC update describing the two most recent swine trH3N2 cases. The “similar” characterization is not very informative. The CDC released sequences from the Kansas infection, but have withheld the sequences from the other cases. Sequences would allow for an analysis of the origins of the infections. Although the CDC has not found community transmission, they have not identified any ill or H3N2 positive swine linked to the patients. Three of the five have no reported contact with swine, while details of the contacts of the other two, who were exposed during state fairs exhibiting swine, remains unclear. The Wisconsin case is 7 months old, and the details of the direct contact are murky. Similarly, the press release on the case in Kansas indicates a child was infected, but the sequences associated with the infection are labeled as originating in an adult (22M).
In addition to the lack of detail on direct exposures, the failure to release the sequences generated from isolates liked to the cases creates ambiguity on the definition of “similar”. If sequences were released phylogenetic analysis could be used to determine the origin of the sequences. If the virus is transmitting within the human population, then the sequences will be closely related and map on the same branch of phylogenetic trees.
However, the release of the Kansas sequences, A/Kansas/13/2009 can be used in phylogentic analysis using public H3N2 swine sequences. Although the number of H3N2 sequences from American swine is limited, such an analysis identifies three HA swine sequences which map to the same branch as the human sequence, A/Kansas/13/2009. The closest match is A/swine/Iowa/03017/2010, followed by A/swine/Illinois/02945/2010, followed by A/swine/Minnesota/578/2007. The similarity between the locations of these closely related isolates with the locations for the initial human cases suggests that the sequences infecting humans are similar and widespread, and minor changes, such as PB1 D618E, which is found in the human trH3N2 sequences as well as virtually all of the human trH1N1 sequences, which are transmitting in humans in a sustained manner.
The “similarity” between the trH3N2 sequences with each other as well as swine in the same areas as the human cases suggest that multiple closely related sequences jumped from swine to humans and is currently concentrated in areas where these swine are found. Consequently, cases are being identified who have no reported contact with swine.
The human cases are hard to detect because the H3 and N2 are of human origin, so they generate positive results with sub-typing reagents and the positive data matches data obtained for seasonal flu.
Sequencing will identify the infections as trH3N2, but such analysis is limited to a small number of labs in the US and worldwide.
Thus, the phylogenetic analysis using the one released human sequence in association with swine sequences suggest that the withheld sequences will map to the same branch as A/Kansas/13/2009, signaling human to human transmission of swine trH3N2.
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