Human Case of Swine Influenza A (H1N1) Triple Reassortant Virus Infection, Wisconsin

Zoonotic infections with swine influenza A viruses are reported sporadically. Triple reassortant swine influenza viruses have been isolated from pigs in the United States since 1998. We report a human case of upper respiratory illness associated with swine influenza A (H1N1) triple reassortant virus infection that occurred during 2005 following exposure to freshly killed pigs.


The Study
On December 7, 2005, a previously healthy 17-yearold boy with no history of recent travel became ill; symptoms were headache, rhinorrhea, low back pain, and cough without fever. He had received inactivated infl uenza vaccine administered intramuscularly on November 11, 2005. During an outpatient clinic visit on December 8, 2005, a nasal wash specimen was obtained and tested positive for infl uenza A by rapid infl uenza diagnostic test (BinaxNow A&B, Binax, Inc., Scarborough, ME, USA). Results of a chest radiograph were normal. The patient's symptoms resolved on December 10, 2005. The specimen was sent to the Wisconsin State Laboratory of Hygiene (WSLH), and an infl uenza A virus was isolated by shell vial tissue cell culture (MDCK cells, WSLH, Madison, WI, USA). Realtime reverse transcription-PCR (rRT-PCR) was positive for infl uenza A virus but negative for human subtypes H1, H3, and Asian avian H5. At the Centers for Disease Control and Prevention (CDC), rRT-PCR testing of the shell vial viral culture material was positive for infl uenza A virus, but negative for human subtypes H1 and H3, as well as avian subtypes H5, H7, and H9. Complete genomic sequencing of the virus at CDC identifi ed it as a swine infl uenza A (H1N1) triple reassortant virus, A/Wisconsin/87/2005 H1N1.
Investigation by the Wisconsin Division of Public Health and the Sheboygan County Division of Public Health showed that the patient had assisted his brother-inlaw in butchering pigs at a custom slaughterhouse 3 days before illness onset. Thirty-one swine were delivered to the facility that morning by a distributor who had acquired the animals from multiple sources. None of the pigs appeared ill. The patient helped hold and abduct the forelimbs of 1 freshly killed pig while his brother-in-law eviscerated it. No facial or respiratory protection was worn during this procedure. A few chickens were housed at the slaughterhouse premises, but no poultry were slaughtered on site.
The patient denied any other contact with swine, poultry, or other animals during the 7 days before becoming ill. Eight days before illness onset, the patient's father obtained a live chicken that was kept in the home for 1 day before it was sacrifi ced during a ritual ceremony. The patient was never within 10 feet of the chicken and did not attend the ceremony. None of the patient's household members or any slaughterhouse employees reported illness during the 2 weeks before or after the patient became ill.
Paired serum specimens were obtained from the pa- lineage) virus, which suggested an acute infl uenza B virus infection. All serum samples were also tested by microneutralization assay at CDC using the patient's swine infl uenza A (H1N1) virus isolate and a human infl uenza A virus (A/ New Caledonia/20/99 H1N1). The patient's serum specimens demonstrated a 2-fold increase in neutralizing antibody titer against swine infl uenza A/Wisconsin/87/2005 subtype H1N1 virus, but the level of neutralizing antibodies to A/New Caledonia/20/99 (H1N1) virus was unchanged in acute-and convalescent-phase serum specimens, which is consistent with his history of infl uenza vaccination in mid-November 2005.

Conclusions
We report a human case of swine infl uenza A (H1N1) triple reassortant virus infection in the United States. The case-patient experienced a mild and acute respiratory illness and recovered fully. Swine infl uenza A/Wisconsin/87/2005 (H1N1) virus was isolated from an upper respiratory specimen obtained from the patient, and serologic testing suggested, but was not diagnostic of, an immune response to acute infection. Epidemiologic investigation showed the patient had direct and close exposure to freshly killed pigs and their organs while assisting his brother-in-law in butchering them. Although the pigs did not appear ill, the most plausible source of the patient's swine infl uenza A virus infection was respiratory secretions of freshly killed pigs.
We were limited in assessing other possible swine infl uenza A (H1N1) virus infections and in confi rming swine infl uenza in the pigs. Pigs delivered to the slaughterhouse the day of the patient's exposure originated from multiple farms, but specimens were unavailable for testing due to delays during animal traceback. Our fi ndings suggest that microneutralization assay may be more sensitive than a standard HI assay in detecting human antibodies to swine infl uenza A viruses. Primers and probes for detection of human infl uenza A viral RNA by rRT-PCR identifi ed a nonhuman infl uenza A virus, triggering further analyses that specifi cally identifi ed the virus. We could not confi rm whether the patient's infl uenza vaccination and high levels of vaccine-derived subtype H1N1 neutralizing antibody infl uenced his relatively mild clinical course of illness. The patient did not have a 4-fold increase in neutralizing antibody titer to the swine infl uenza A (H1N1) virus isolated from his respiratory specimens, which would be more suggestive of acute infection. Further studies are needed to understand the human immune response to infection caused by swine infl uenza A viruses and to interpret serologic test results.
Human infections with novel infl uenza A subtype viruses are now nationally notifi able in the United States. Clinicians should inquire about exposure to animals (including pigs) and visits to petting zoos and county fairs when evaluating patients with unexplained infl uenza-like illnesses (15). Ideally, joint animal health and public health investigations should be conducted promptly to identify and control the source of swine infl uenza. Investigations should attempt to specifi cally identify the virus in animals and persons; defi ne the scope and clinical spectrum of human illnesses, including appropriately timed collection of serum specimens from ill persons and exposed individuals; determine risk factors for human infection; and assess the potential for human-to-human transmission of swine infl uenza A viruses.