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Commentary
Human
Transmission of trH1N1 trH1N2 trH3N2
Recombinomics
Commentary 22:55
November 23, 2010
However, in addition to trH3N2 sequences, the CDC also released swine sequences from humans, going back to the 1990’s. The earlier sequences were classical swine H1N1 and were closely related to each other, although the collections were over an extended period (many years). The close relationship suggested swine sequences were transmitting in humans.
The concern was increased when the sequence from a patient in Illinois (58F) was released, A/Illinois/09/2007. Earlier sequences from an outbreak at the Huron County fair in Ohio were also released. These sequences were of interest because trH1N1’s were isolated from two exhibitors (A/Ohio/01/2007 and A/Ohio/02/2007), and two dozen others who had contact with swine at the fair also had ILI-symptoms, which was unusual for August in Ohio. Full sequences from the swine were released (A/swine/Ohio/24366/07 and A/swine/OH/511445/2007), and the HA sequences exactly matched the exhibitors.
The recently released sequences from the human isolates in Ohio demonstrated matches with the internal genes from the swine, as well as the recent trH3N2 cases. However, these matches, including HA, also were found in the Illinois case. The human samples in Ohio were collected on August 17, 2007, while the human sequence in Illinois was two weeks later, September 1, 2007. The HA and PB1 sequences were identical, signaling human transmission.
Although the human sequences in Ohio matched the swine in Ohio, the direction of the transmission remains unclear. The NEJM paper assumed that the swine infected the exhibitors, but the clustering of human cases suggests it was the other way around. The NEJM paper included accession numbers for HA sequences from five cases, but the identity between the Illinois and Ohio cases was not documented or discussed. The absence of these sequences led to interpretations not supported by the data.
The similarity between the HA sequences of human cases from Ohio and Illinois was extended by the internal genes, which were similar to each other, but also were closely related to a case in Michigan, A/Michigan/09/2007, which was H1N2. These similarities also supported transmission in humans.
The transmission was supported further by the recently released sequences from the H3N2 cases. The NS genes from the four H3N2 cases collected in 2009 and 2010, were most closely related to the human H1N2 cases isolated 2-3 years earlier in 2007. The branch with these five sequences, collected more than three years apart has no swine sequences (see examples here here here here), once again supporting human to human transmission over an extended period.
This clustering of human sequences is not compatible with swine to human explanations, which are frequently linked via a very loose association, such as the Illinois patient who had visited a state fair but had no contacts with the pigs or pig pen. Lack of contact has also been described for the recent trH3N2, lending more support for extensive human to human transmission of swine derived isolates, including trH1N1, trH1N2, trH3N2.
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