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CDC's Definition of Swine Exposure For trH3N2 Cases
Recombinomics Commentary 21:15
November 22, 2011

Reported cases of Human Infection with Swine Origin Influenza A (H3N2)
Cs   Age   Onset       Swine Exposure                  Strain Designation
 1    Child  July, 09    Visit local animal fair           A/Kansas/13/2009
 2    Child  Sept, 09   No reported exposure        A/Iowa/16/2009
 3    Child  May, 10    Visit live animal market      A/Minnesota/09/2010
 4    Child  Sept, 10   Visit local animal fair          A/Wisconsin/12/2010
 5    Adult  Oct, 10     No direct exposure              A/Pennsylvania/14/2010
 6    Child  Sept, 10   Visit local animal fair           A/Pennsylvania/40/2010
 7    Adult  Nov, 10     Visited live animal market  A/Minnesota/11/2010
 8    Child  Nov, 10     No direct exposure             A/Minnesota/11/2010
 9    Child  July, 11      No direct exposure             A/Indiana/08/2011
10   Child  Aug, 11     Visit county animal fair       A/Pennsylvania/09/2011
11   Child  Aug, 11     Exhibited market hogs       A/Pennsylvania/10/2011
12   Child  Aug, 11     Visit local animal fair          A/Pennsylvania/11/2011
13   Child  Oct, 11      Visit local animal fair          A/Maine/06/2011
14   Adult  Oct, 11      Visited local farms              A/Indiana/10/2011
15   Child  Oct, 11      Contact local farm              A/Maine/07/2011

The above data summarizes the 15 trH3N2 cases in the United States.  The first seven cases (in red) are from the CDC presentation at the FDA’s Feb, 2011 advisory committee meeting on vaccine selection.  The descriptions of the “swine exposure” above are from slide 4 in the presentation, and begin to address media claims that the human cases represent sporadic jumps from swine to humans, as well as ProMED claims that most of the 2011 cases are associated with close contacts with swine.  The CDC presentation also included phylogenetic analysis of the 2009 / 2010 cases along with swine and earlier Canadian H3N2cases in the HA (slide 6) and NA (slide 7) trees (which also have swine H1N2 in the NA tree).

The HA tree shows clustering of the 2010 HA sequences, with 4 of the 5 sequences on the same branch at the top of the tree (which would also include the daughter of the index case of the Minnesota cluster, A/Minnesota/11/2010, who had no swine exposure and was lab confirmed with serological testing).

The clustering of the 2010 HA sequences was also seen for the 6 internal gene segments (not shown in the CDC presentation), signaling adaptation to humans.  The clustering of the human sequence was extended in 2011, where all seven isolates matched each other in all 8 gene segments, including the earlier isolates for 6 of the 8 genes.  The NA matched A/Pennsylvania/14/2010, while the M gene matched H1N1pdm09, which was critical for the jump from swine to humans. 

Thus, the sequence data clearly supports transmission In humans.

This transmission is also supported by the nature of the “swine exposure”  In the 8 cases prior to 2011, three had no reported swine exposure while the remain five involved visits to state fairs or live markets with minimal swine contact, if any.  The CDC acknowledged human to human transmission for the Minnesota cluster because trH3N2 was serologically confirmed in the daughter, who had no swine exposure, and trH3N2 was isolated from the father.

The CDC also acknowledged human to human transmission for the first 2011 case, since there was no direct swine contact.  Human transmission was cited because the caretaker for the patient had swine exposure in the weeks priort o the case.  However, the caretaker was asymptomatic, as were her contacts, including the swine.  Thus, the human transmission from the caretaker was purely speculative.

Similarly, most of the other 2011 cases involved visits to fairs.  All three Pennsylvania cases visited the Washington county fair, and only one case, A/Pennsylvania/10/2011, had direct contact with swine because she exhibited market hogs.  However, the hogs were asymptomatic, as were all swine at the fair.

Both Maine cases also attended an agricultural fair, Fryeburg, which did have symptomatic swine.  However, the symptomatic swine tested negative for SOIV’s.  The second Maine case, A/Maine/07/2011, also participated in a pig scramble at the fair, but the fair ended Oct 9, and two weeks prior to disease onset on Oct 22.  The patient also had a swine exposure after the fair, and the nature of the contact was unclear, but the swine were also asymptomatic.

The second case in Indiana, A/Indiana/10/2011, was a veterinarian, but his swine exposure was investigated by the Indiana Board of Animal Health, and the investigation failed to identify any swine with symptoms in the 30 days prior to expose to the veterinarian.

Thus, there is little evidence for transmission of trH3N2 from pigs to people.  The swine exposures were largely limited to children who attended state fairs, with minimal contact with swine. 

The linkage to swine is largely driven by testing of those with swine contact.  Maine has only identified two influenza cases this season, and both were trH3N2 cases.  Similarly, Indiana has only identified three cases since late July, and two of the three are trH3N2.  The CDC has only sequenced two H3N2 cases in Pennsylvania beyond the three trH3N2 cases, and both seasonal H3N2 cases were adults.  Thus, all three of the adolescent cases in Pennsylvania were trH3N2 cases.

Testing is driving the detection of trH3N2 cases, not swine exposure. 

Only one example of the novel trH3N2 identified 2011 has been found in swine,
A/swine/NY/A01104005/2011, which was from an sample collected after (Sept 13) the identification of cases in Indiana and Pennsylvania.

Expanded testing, with a focus on children, is long overdue.

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