Agricultural Pesticides and Shingles Risk in a Prospective Cohort of Licensed Pesticide Applicators

Abstract

Background: Some pesticides are immunotoxic and have been associated with an increased risk of immune-mediated diseases. The risk of shingles, the clinical reactivation of varicella-zoster virus, increases with aging and immunosuppression; little is known about its associations with pesticides.

Objective: We examined the use of agricultural pesticides in relation to incident shingles in a prospective cohort of licensed pesticide applicators.

Methods: The study sample included 12,820 (97% male) farmers (enrolled in 1993-1997 in North Carolina and Iowa), who were followed for a median of 12 y (interquartile range: 11-13). Shingles was self-reported at enrollment and at follow-up. We evaluated ever-use of 48 agricultural pesticides reported at study enrollment in relation to shingles risk and considered exposure-response for intensity-weighted lifetime days (IWLDs) of use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models, adjusting for state, and allowing estimates to vary by median attained age (60 y).

Results: Incident shingles was reported by 590 participants. Associations were positive ($\text{HRs}>1.2$) for ever- vs. never-use of eight insecticides, three fumigants, two fungicides, and five herbicides, and exposure-response trends were seen across increasing quartiles (Q3 and $Q4>Q1$) or tertiles (T3 and $T2>T1$) of IWLDs for four insecticides [permethrin (crops), coumaphos, malathion, and lindane], two fumigants (carbon tetrachloride/carbon disulfide and methyl bromide), and three herbicides [alachlor, trifluralin ($<60\text{years of age}$) and 2,4-dichlorophenoxyacetic acid]. Shingles was not associated with total years or days per year mixed or applied any pesticides, but in older participants, shingles was associated with a history of a high pesticide exposure event [$\text{HR}=1.89$ (95% CI: 1.45, 2.45)].

Conclusions: Several specific pesticides were associated with increased risk of shingles in farmers, especially at higher levels of cumulative use. These novel findings, if replicated in other populations, could have broader implications for the potential effects of pesticides on vaccine efficacy and susceptibility to other infections. https://doi.org/10.1289/EHP7797.

Figure 1.

Risk of shingles associated with greater cumulative intensity-weighted days of specific pesticide use. Pesticides (including insecticides, fumigants, fungicides, and herbicides) with at least 10 exposed cases per quartile (Q) or tertile (T), for selected results showing a pattern of increasing HRs in higher quartiles or tertiles (i.e., Q3 and $\mathrm{Q}4>\mathrm{Q}1$; T3 and $\mathrm{T}2>\mathrm{T}1$, or with one or more HRs for the upper quartiles or tertile with CIs excluding the null. Complete results are shown in Table S3. HRs are based on Cox proportional hazard models and 95% confidence limits with age as the time scale, were allowed to vary by median attained age (60 y). All models include state; metalaxyl was adjusted for methylbromide, metribuzin was adjusted for imazethapyr. Note: 2,4-D, 2,4-dichlorophenoxyacetic acid; HR, hazard ratio.