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Commentary
Novel Influenza
Limited Human Transmission Myth
Recombinomics Commentary 11:15
December 18, 2011
Preliminary evidence from the investigation of these cases in Iowa shows no evidence of ongoing transmission among humans.
The above comments are from the CDC early release MMWR entitled, “Limited Human-to-Human Transmission of Novel Influenza A (H3N2) Virus — Iowa, November 2011”. The report describes confirmed and suspected human to human transmission in two families, epidemiologically linked through a day care center. The index case (3F – A/Iowa/07/2011) attended a day care center with two brothers (2M and 1M) from the other family who were confirmed to also be infected by the same H3N2pdm11 (A/Iowa/08/2011 and A/Iowa/09/2011). Full sequences were generated from isolates form all three cases and sequences from the 8 gene segments were identical or differed by a single nucleotide when compared to the index case, confirming human-to-human transmission. Moreover, the brother and father of the index case were symptomatic, but not tested.
The confirmed and suspect cases, as well as the sequence data, signaled efficient transmission, even though the samples were collected at the beginning of the 2011/2012 flu season when efficient transmission of seasonal flu was rare.
These three confirmed cases were preceded by seven cases with matching lineages for all eight gene segments, signaling sustained transmission of this sub-clade over a wide geographical region (Iowa, Indiana, Pennsylvania, Maine). The earlier cases were not epidemiologically linked and represented multiple independent introductions, even within states and over a short time frame. Moreover, the sequences had multiple examples of reassortment within the sub-clade, also supporting widespread infections in humans. To date this sub-clade has been identified in one swine isolate, from a sample collected after the four confirmed cases in Indiana and Pennsylvania, suggesting the swine case was due human infection crossing back to swine.
The CDC uses negative data, along with a “no evidence of” statement to claim that the transmission was limited and attributes earlier cases to direct or indirect “swine exposure”. However, the CDC epidemiological studies have failed to identify a source for any of the 17 human trH3N2 cases or the 1 human trH1N2 case in 2010 and 2011, all of which have a H1N1pdm09 PB1 polymorphism E618D, or an H1N1pdm09 M gene, and all of which have evolved from the human cases identified in 2010.
The “swine exposure” cases are part of a CDC program that targets cases with swine exposure during the off season, when seasonal flu frequencies are low. These cases are identified through cross reactivity with seasonal H3 or swine NP targets, which can give anomalous results if the RNA levels are low, which is common in the “off season”. Thus, in several instances the PCR data indicated the infection was seasonal H3 or unsubtypable, but trH3N2 infections were confirmed by sequencing.
Public sequences of 2011/2012 cases that are under ten have been dominated by novel cases (7/8), including the five most recent sequences which are from cases with no swine exposure (A/Iowa/07/2011, A/Iowa/08/2011, A/Iowa/09, A/Minnesota/19/2011, A/West Virginia/06/2011). The other two case this season (A/Maine/06/2011 and A/Maine/07/2011) were from cases with swine exposure, but the sequences were virtually identical and no SOIV infected swine have been identified in Maine. A/Maine/07/2011 is one of the cases that typed as H3, but was sequenced because of swine exposure, and was found to be H3N2pdm11. In Maine, the only two confirmed cases this season are the two cases above. Similarly, in West Virginia there have only been two confirmed case, A/West Virginia/06/2011, and a contact that is under investigation at the CDC. Thus, in Maine and West Virginia, the only PCR confirmed case have been confirmed or suspected of being novel.
These states suggested that the limited transmission cited by the CDC are only limited by the same factors which limit the detection of sustained transmission of seasonal flu at this time of the year, and as conditions for sustained transmission improve, the clusters of confirmed or suspect cases in Maine, Iowa, Minnesota, and Iowa will grow.
The sequence data, including the co-circulation of three different constellations of novel influenza (H3N2pdm11, trH3N2, trH1N2) clearly demonstrates sustained transmission since July, and the lack of additional examples is due to seasonal factors and a failure of the CDC to increase surveillance of cases under the age of 10, including a significant increase in the sequencing influenza A positive cases.
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