Use of specific pesticides is associated with increased risk of developing shingles in the Agricultural Health Study

Abstract

BACKGROUND: Some pesticides are immunotoxic and may increase risk of immune-mediated diseases. Risk of shingles, the clinical reactivation of varicella zoster virus (VZV), increases with aging and immunosuppression; little is known about associations with pesticides. OBJECTIVE: We evaluated pesticide use in relation to incident shingles among licensed pesticide applicators in the Agricultural Health Study, a prospective cohort in Iowa and North Carolina. METHODS: We identified 590 incident shingles cases among 12,820 applicators (97% male farmers) enrolled in 1993-7 and followed for a median of 12 years (IQR 11,13). We evaluated associations with ever-use of 48 pesticides reported at enrollment and examined exposure-response trends for cumulative intensity-weighted lifetime days of use. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models, adjusting for state and correlated pesticides, and allowing estimates to vary by median age of cases (60 years). RESULTS: Shingles risk was associated with ever-use of 14 pesticides (5 insecticides, 2 fumigants, 2 fungicides, and 5 herbicides (HRs 1.22 to 1.94). Increasing exposure-response trends (p<0.01) were seen for four insecticides (coumaphos, carbaryl, diazinon, permethrin on crops), two fumigants (methyl bromide, carbon tetrachloride), and two herbicides (trifluralin, and 2,4-D). In older participants, shingles was associated with self-reported history of a high pesticide exposure event (HR 1.89; 95%CI 1.45, 2.45). Findings were similar after excluding those with a history of leukemia/lymphoma or autoimmune diseases. CONCLUSIONS: Specific pesticides were related to shingles risk in farmers, with several demonstrating exposure-response trends. These novel findings support further investigation of pesticides in relation to shingles risk and VZV immunity. Some pesticides may compromise cell-mediated immune responses to VZV, as seen with aging and immunosuppressant medications, which may have broader implications for vaccine efficacy and susceptibility to other infections.