Swine workers and swine influenza virus infections

Emerging Infectious Diseases, Dec, 2007 by Gregory C. Gray, Troy McCarthy, Ana W. Capuano, Sharon F. Setterquist, Christopher W. Olsen, Michael C. Alavanja, Charles F. Lynch

In 2004, 803 rural Iowans from the Agricultural Health Study were enrolled in a 2-year prospective study of zoonotic influenza transmission. Demographic and occupational exposure data from enrollment, 12-month, and 24-month follow-up encounters were examined for association with evidence of previous and incident influenza virus infections. When proportional odds modeling with multivariable adjustment was used, upon enrollment, swine-exposed participants (odds ratio [OR] 54.9, 95% confidence interval [CI] 13.0-232.6) and their nonswine-exposed spouses (OR 28.2, 95% CI 6.1-130.1) were found to have an increased odds of elevated antibody level to swine influenza (H1N1) virus compared with 79 nonexposed University of Iowa personnel. Further evidence of occupational swine influenza virus infections was observed through self-reported influenza-like illness data, comparisons of enrollment and follow-up serum samples, and the isolation of a reassortant swine influenza (H1N1) virus from an ill swine farmer. Study data suggest that swine workers and their nonswine-exposed spouses are at increased risk of zoonotic influenza virus infections.

**********

Since 1997, numerous instances of avian influenza virus infection have been documented in humans (1). The latest of such viruses, strains of subtype H5N1, have rapidly spread among domestic bird species across several continents and caused disease in >330 humans since 2003 (2). Like the influenza (H5N1) viruses that are circulating today, a highly virulent avian virus subtype, H1N1, was responsible for the 1918-1919 pandemic. Coincident with the human pandemic, this virus also infected swine, caused large-scale epizootics of swine respiratory disease in the midwestern United States, and established itself among pigs as the "classical" swine influenza virus lineage of influenza (H1N1) viruses (3,4). It also apparently moved from swine to humans, causing illness among farmers (3). Anticipating that the next pandemic virus may similarly be readily transmitted among and between pigs and humans, we sought to prospectively study swine workers for risk factors for swine influenza virus infection.

Methods

Study Population

After institutional review board approval, participants were recruited from the 89,658-person Agricultural Health Study (AHS) cohort (5) by using an informed consent process. The cohort, first assembled from 1993 through 1997, comprises primarily private pesticide applicators (predominately farmers) and their spouses living in Iowa and North Carolina. Through a stratified sampling scheme, participants living in Iowa were selected by previously reported exposures to swine or poultry, age group, sex, and proximity to the University of Iowa in Iowa City. Nonswine- and nonpoultry-exposed potential participants were similarly selected.

Potential AHS participants and their spouses were screened by telephone interviews and verified to be without immunocompromised conditions and without a history of accidental injection with swine influenza vaccines. They were then invited to participate in a 2-year prospective study of zoonotic influenza transmission. Enrollments were made through personal interviews held in 29 of the 99 counties in Iowa during the fall of 2004. After informed consent was obtained, each participant completed a questionnaire and permitted serum sample collection. Swine exposure was assessed by the participant's response to the enrollment question: "How many years have you worked in swine production?" Participants who answered "never" were classified as nonexposed. Follow-up visits with similar questionnaires and phlebotomy were scheduled at 12 and 24 months. Upon enrollment and at 12 months, participants were given a first-class US Postal Service-ready kit with detailed instructions to complete another questionnaire and self-collect gargle and nasal swab specimens within 96 h of symptom onset if they met a case definition of influenza-like illness (fever [greater than or equal to] 38[degrees]C and a cough or sore throat). The kit contained a freezer block that participants were asked to insert into the preaddressed shipping box before dropping off specimens and questionnaires with the US Postal Service. The US post office near the University of Iowa laboratory kept these boxes refrigerated until the study team picked them up on regular work days.

Data and serum samples from nonagricultural health study controls from a concurrent cross-sectional study (6) were included in population comparisons at enrollment. Study controls were generally healthy University of Iowa students, staff, and faculty who denied having swine or poultry exposures. They were not studied at 12 and 24 months after enrollment.

Laboratory Methods

Specimens

Gargle and swab specimens were transported to the University of Iowa by the US Postal Service in Micro Test M4RT Viral Transport Media (Remel, Inc., Lenexa, KS, USA) and preserved at -80[degrees]C. These specimens were studied with both culture in MDCK cells and R-Mix FreshCells (Diagnostic Hybrids, Inc., Athens, OH, USA) and with molecular techniques.