During the past 60 years, the US swine industry has changed in composition from primarily small herds on family farms to include immense herds in large, corporate facilities (). The US pork industry now generates $11 billion annually and employs an estimated 575,000 persons (2002 figures) [24
]. Although pork production facilities today are larger, fewer, and more efficient and require fewer workers, it is estimated that, nationwide, at least 100,000 workers work in swine barns with live pigs (Dr. Liz Wagstrom, personal communication).
Figure 1 Trends in hog operations in the United States. Adapted from .
Iowa is the leading swine-producing state in the United States, with 9300 farms [25
] (2004 figure), raising 25 million hogs per year [25
] (a rate of 8.6 swine per human resident [26
]). Today's large herds are maintained through the frequent introduction of young swine into swine-producing facilities. This constant influx of potentially pathogen-susceptible animals makes swine pathogen eradication difficult to achieve. Therefore, swine influenza infections, which were formerly seasonal (like human influenza infections), now have become enzootic, and swine influenza transmission occurs year-round in much of the US swine industry. Although these influenza virus infections among pigs are generally thought to be mild, they provide a constant opportunity for zoonotic influenza virus infections among humans who are occupationally exposed. Continual swine influenza transmission in US swine herds also provides the opportunity for human influenza viruses to mix with swine or avian influenza viruses and generate novel progeny viruses.
The potential for animal-to-animal transmission (reflected in the basic reproductive number, R0
) among pigs in a swine confinement operation will be much greater than on a traditional farm because of the pigs' crowding (resulting in prolonged and more frequent contact). In addition, virus-laden secretions from pigs may be more concentrated, and reductions in ventilation and sunshine exposure may prolong viral viability. Thus, a confinement operation worker's probability of acquiring influenza virus infection may be increased, compared with that of a traditional swine worker, and certainly increased when compared with the risk among non–swine workers exposed only to human-to-human influenza activity. This risk is even greater if the virus does not kill pig hosts and if new susceptible animals are frequently introduced to the farm, sustaining transmission. Swine workers may initiate epidemics by enhancing the mixing of viral strains that may lead to reassortment and novel progeny influenza viruses of pandemic potential. They may serve as a conduit for a novel virus to move from swine to man or from man to swine. One might envision that, once a novel virus is introduced into a densely populated swine barn, the viral loads swine workers would experience could overwhelm any partial immunity they might possess. After work, they may readily communicate that virus to their family members and neighbors. Similarly, they might introduce a novel human virus to crowded swine populations, which could have tremendous economic impact on the US agricultural industry. Recall that during the 1918–1919 human influenza pandemic, there were concomitant US swine herd die-offs (likely from the virus) that caused much economic hardship [27
Human infections with swine influenza virus have been previously described. In 1988, swine influenza virus exposures at a Wisconsin county fair led to infections in at least 50 swine exhibitors and 3 of their family members, and infection resulted in the death of a previously healthy woman who attended the fair [28
]. Although many swine influenza virus infections in humans are likely mild or asymptomatic, the potential for a virulent, highly communicable novel virus to move from swine to man seems to be great.
There are 3 developments that heighten our awareness of this threat. First is our new understanding of how common these infections must be—thus, the importance of this report. Second is the recent change in animal husbandry in the US pork and poultry industries. Today, tens of thousands of susceptible pigs or poultry are housed in confinement facilities, serving as a tremendous potential reservoir of susceptible animals, whose dense populations may hasten viral mutation and reassortment. The third development of concern is the sudden emergence and rapid spread of very virulent H5N1 virus that is now endemic in many parts of Asia and that has spread via migrating birds to Russia. Fortunately, although this virus infects swine, as yet, it is not readily transmissible between pigs [29
]. However, the H5N1 virus is readily transmitted among domestic birds and waterfowl. Therefore, if migrating birds were to introduce the virus to North American pork production facilities, and if the virus were to prove to be efficient in transmission, the resultant swine-to-human swine virus infections could result in considerable human morbidity. Even with modern industry biosecurity measures, transmission would be difficult to control. Additionally, as much of the pork industry is rural, detection of such a novel virus invasion could be delayed, especially if the virus does not readily kill swine.
The elevated serologic responses to swine H1N1 virus among farmers and veterinarians observed in this study are consistent with a previous study of these occupational groups [20
]. Our study found seropositivity to swine H1N2 among farm workers that had not been previously detected. All 3 swine exposure groups had elevated titers against the swine H3N2 virus. Strong association of this virus with human H3N2 virus (A/Nanchang/933/95) suggests cross-reactivity between swine and human strains, which was not unexpected, because the swine H3N2 virus HA gene is of human origin [17
]. Although meat processing workers were at increased risk for antibodies against swine H1N1 and swine H1N2 virus, their ORs were lower than those for farmers and veterinarians. We speculate that this may be the result of limited exposure to live pigs.
Our study is unique, because to our knowledge, this is one of the largest such serologic assessment to date of occupational transmission of swine virus to human infections. Serologically, we studied the antibody response to 2 recently emerged circulating swine viruses in a state with year-round, active virus transmission within swine herds. In addition, we controlled for the confounding of serologic response to human influenza virus as an explanation for increased serologic response to the swine viruses and employed proportional odds modeling to better discriminate the effect of potential risk factors to the swine virus serologic outcomes.
This study has a number of limitations. There was a lack of detailed exposure information for the farmer group, and the study design did not allow us to determine whether individuals developed clinical symptoms with seroconversion. It is possible that the elevated titers compared by proportional odds modeling do not correlate with infection. However, our exposed populations had statistically significant evidence of swine virus infection by both the proportional odds modeling and the more traditional use of a titer cutpoint. Our choice of a ≥1:40 cut-point is consistent with the literature [20
] but could also be viewed as conservative. In prospective cohort studies, Fox et al. [30
] demonstrated that, among children, HI titers of ≥1:20 against human H1 virus were protective and that almost any titer detected among adults was evidence of protection. We are presently conducting a large, prospective study of swine-exposed workers to better understand occupational zoonotic influenza infection.
We have documented evidence for swine influenza virus infection among 3 different occupational groups with exposure to pigs. Each of the 3 groups had antibody evidence of infection with 2 different swine viruses, and their odds of elevated serologic titers were much greater than those for control subjects. Serologic risk factor data controlled for potential confounders, such as serologic response to human influenza virus and vaccine. Study laboratory findings were validated by a blinded external laboratory, and serologic assay results were corroborated by studies of virus-specific antisera. We argue that these data are compelling evidence that swine influenza virus infections frequently occur among swine workers. It seems prudent to consider swine workers for sentinel influenza surveillance and routine human inactivated influenza vaccine immunizations. Additionally, in the event of heightened pandemic threat, protection of swine-exposed workers with antiviral medications and pandemic strain vaccines seems to be an important strategy to limit the spread of influenza virus among human and susceptible domestic animals.