Neurologic Symptoms Associated With Cattle Farming in the Agricultural Health Study

Recent research1,2 indicates that occupational exposure to farm animals at several stages of food production may be an important source of exposure to pathogens. The bacterial pathogen Campylobacter jejuni is particularly common in poultry but can also colonize swine and other livestock, including cattle.3 Campylobacter spp. is the most commonly identified bacterial cause of foodborne illness in the United States,4 and campylobacteriosis is the leading cause of bacterial diarrhea worldwide.5 Although food-borne exposure is an important source of Campylobacter infection, case–control studies6,7 have demonstrated significant positive associations between exposure to farm animals, including cattle, and Campylobacter infection. Elevated levels of anti–C. jejuni antibodies have been reported in meat processing workers,8 poultry workers,9 and slaughterhouse workers.2 Infection with C. jejuni is the most frequently identified antecedent to Guillain-Barre Syndrome (GBS), an autoimmune peripheral neuropathy.10–12 GBS is the leading cause of acute flaccid paralysis in the United States and worldwide.13 The incidence of GBS after C. jejuni infection has been estimated to be about 1.17 per 1000 person-years, but certain strains of C. jejuni are more strongly associated with GBS.14,15 Evidence indicates that the mechanism for the association between C. jejuni exposure and GBS involves molecular mimicry between C. jejuni lipo-oligosaccharides and peripheral nerve gangliosides.16–21 Peripheral neuropathy, whether motor or sensory, can have varying degrees of severity and can be due to various causes. In GBS, the mechanism of neuropathy is autoimmune. The two most prominent types of GBS are acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is the most common type of GBS in North America and Europe, and acute motor axonal neuropathy (AMAN), which is most common in China and Mexico.12,22,23 Weakness is a symptom of both AIDP and AMAN, whereas numbness is more associated with AIDP. In addition to GBS with its acute manifestation, there also is a disease with a longer but heterogeneous course, called chronic inflammatory demyelinating polyradiculoneuropathy, which also exhibits features characteristic of autoimmune disease.24,25 AMAN is most strongly associated with C. jejuni infection, but there is evidence that other forms of autoimmune peripheral neuropathy may be associated with C. jejuni as well.26 Although the symptoms of GBS are often severe, with 80% to 90% of GBS patients becoming unable to walk during their illness, we hypothesize that some people exposed to C. jejuni may experience subclinical, or less severe, symptoms of autoimmune peripheral neuropathy.27,28 Despite the evidence that occupational exposure to animals may be an important source of Campylobacter infection, few studies have examined these exposures to C. jejuni as a risk factor for development of peripheral neuropathy. In 2007, Price et al9 reported for the first time that poultryhouse workers (n = 20) had significantly increased odds of reporting symptoms of peripheral neuropathy compared with community referents (n = 40). Furthermore, among men reporting poultry contact (n = 18), levels of anti–C. jejuni antibodies were significantly higher, and immunoglobulin G antiganglioside autoantibodies associated with autoimmune peripheral neuropathy were increased as compared with male controls (n = 18), but with borderline statistical significance (P = 0.074).9 Davis et al29 used the large sample size of the Agricultural Health Study (AHS) to build on the findings of Price et al, documenting that self-reported work with swine or with both swine and poultry was significantly associated with symptoms of peripheral neuropathy. Campylobacter has been of particular concern in poultry, but there has also been recent attention to the role of cattle as reservoirs of Campylobacter.30 We hypothesize that occupational exposure to cattle may increase the risk of C. jejuni–associated autoimmune peripheral neuropathy, including less severe, or subclinical, peripheral neuropathy. This study examines the association between occupational exposure to dairy or beef cattle and neurologic symptoms in AHS participants.