Humans, pigs, and avian species are inextricably linked in influenza transmission. The 1918, 1957, and 1968 pandemic influenza viruses all had structural components from an avian influenza virus (24
). During the 1918 pandemic, a concomitant epizootic of swine influenza spread across the US Midwest (4
). Numerous anecdotal accounts described influenza-like illnesses developing in farmers and their families after contact with ill swine and of swine developing symptoms of swine influenza after contact with ill farmers (3
). Since the 1918 pandemic, human influenza viruses have infected swine (25
) and swine influenza viruses have occasionally caused recognized disease among humans (27
). Swine influenza transmission is known to occur nonseasonally and sporadically in the US swine population. Approximately 25%–33% of 6- to 7-month-old finishing pigs and 45% of breeding pigs have antibodies to the classic swine influenza (H1N1) virus (28
). Anticipating that the next pandemic influenza virus may be efficiently transmitted from swine to swine and between swine and humans, we examined risk factors for previous and incident swine influenza virus infections in humans as surrogates for pandemic virus risk among those occupationally exposed to swine.
Study results suggest that swine workers are at markedly increased risk for swine influenza virus infections. Swine workers (AHS swine-exposed) had >50 times the odds of elevated antibodies against the classic swine influenza (H1N1) virus and remarkably, the AHS nonswine-exposed (mostly spouses of swine-exposed participants) also were at increased risk, with >25 times the odds of influenza (H1N1) infection compared with truly nonexposed controls (university controls). These ratios suggest that the AHS nonswine-exposed participants acquired infection either through indirect exposure to swine (e.g., handling dirty laundry or exposure to other fomites), misclassification (did not report direct contact with swine but did occasionally enter a swine barn), or exposure to their spouses who were shedding swine influenza viruses. Although the latter explanation is likely a rare event, even spouses who reported never living on a swine farm had increased odds of elevated antibody titers (data not shown). These findings should be tempered with the acknowledgment that laboratory-based evidence for human-to-human transmission of swine influenza viruses is sparse in medical literature.
Consistent with our previous report (7
), among the significant unadjusted risk factors, we found exposure to nursery pigs was associated with an increase in antibody titer over time to swine influenza (H1N1) virus (Appendix Table
; OR 1.5, 95% CI 1.1–2.1), but being male was a stronger predictor. Among the participants who seroconverted to >
1 of the swine viruses, <25% reported an influenza-like illness during the 2 years of follow-up, which suggested that most swine influenza virus infections are mild or subclinical. Among the 66 study participants with influenza-like illness who submitted 74 sets of gargle or nasal swab specimens through the US postal system, 22 cultures showed influenza A virus and 1 (4.5%) showed swine influenza virus.
This study has a number of limitations. Participation was voluntary, and participants might have been more likely to suffer zoonoses than their peers. Exposure data were collected through self-report, were unverified, and were subject to recall and other biases. University controls were younger than AHS participants and had substantially fewer years of life to come in contact with influenza viruses. Although age was selected in only 1 of the final multivariable models (), we checked for age difference confounding by forcing age in each of the other final multiviariate models, and the covariates presented in and remained statistically significant (data not shown). As the study HI assays are strain dependent, a mismatch between circulating human or swine strains and those we used for the assays could have resulted in inaccurate estimates of risk.
Additionally, there was likely some confounding effect on antibodies against human influenza virus reacting in the HI assays against swine influenza virus. We attempted to control for potential cross-reactivity through statistical adjustments. However, these and the other demographic risk factor adjustments could have been inadequate to isolate swine exposure risk factors. Further, our detection of incident influenza virus infections was suboptimal. Paired sera were collected 12 months apart, which likely permitted some influenza virus infection to be missed. Also, because of the wide dispersal of study participants, we relied upon self-identification of influenza-like illness, self-collection of nasal and gargle specimens, and shipping of specimens by the US postal system, all likely reducing the probability of identifying influenza virus infections. Even so, we detected both serologic and culture evidence of incident swine influenza virus infections. This study is unique in that a large cohort of rural farmers, many with swine exposures, were prospectively followed for influenza-like illnesses. The aggregate study data clearly documents increased occupational risk of swine influenza virus infection for these workers and their nonswine-exposed spouses.
As our study data suggest, swine influenza virus infections in humans are often mild or subclinical; however, when detected they can be quite serious. Myers et al. recently reviewed the 50 cases in the medical literature and found the overall case-fatality rate to be 14% (27
). Human clinical morbidity and mortality rates would likely be increased if a pandemic virus’s effect on rural communities were amplified by infection in swine herds. Thus, our data have important public health implications. With risk for infection so high and exposure so common, swine workers should be considered for special public health interventions (1
). To our knowledge, there is no US national or state policy that offers swine workers priority access to annual influenza vaccines, pandemic vaccines, or influenza antivirals as part of influenza pandemic planning. These workers are also not considered a high priority for influenza surveillance efforts.
Protecting swine workers from influenza viruses will also benefit those with whom they have contact, namely family members, as well as the swine herds for which they care. Assuming an influenza virus may readily move among and between species, recent modeling studies have shown that such workers could accelerate an influenza epidemic among nonswine workers in their communities as much as 86% (30
). Additionally, there is now extensive evidence for human influenza virus reassortment with swine and/or avian viruses in pigs (9
). Encouraging swine workers to receive annual influenza vaccines will reduce their potential role in the genesis of novel influenza strains. Our study results corroborate the numerous arguments (1
) that protecting swine workers from human and zoonotic influenza makes good public health sense.