Associations of exposure to perfluoroalkyl substances individually and in mixtures with persistent infections: Recent findings from NHANES 1999-2016

Abstract

Certain viruses and parasites can cause persistent infections that often co-occur and have been associated with substantial morbidity and mortality. Separate lines of research indicate exposures to per- and polyfluoroalkyl substances (PFAS) suppress the immune system. We hypothesized that PFAS exposures might systematically increase susceptibility to persistent infections resulting in a higher pathogen burden. We used data from 8778 individuals (3189 adolescents, 5589 adults) in the nationally-representative U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2016 to examine cross-sectional associations between serum concentrations of four highly detected PFAS (PFOS, PFOA, PFHxS, PFNA) with the presence of antibodies to cytomegalovirus, Epstein Barr virus, hepatitis C and E, herpes simplex 1 and 2, HIV, T. gondii, and Toxocara spp. Seropositivity was summed to calculate a pathogen burden score reflecting the total number of infections. Separate survey-weighted multivariable regression models were fitted to analyze PFAS individually and quantile g-computation was used to analyze PFAS mixtures. Among adolescents, 38.7% had at least one persistent infection while 14.9% had two or more; among adults, these percentages were 48.0% and 19.7%. Each PFAS was individually associated with significantly higher pathogen burdens and the most pronounced associations were observed in adolescents [e.g., among adolescents, a doubling of PFOS was associated with 30% (95% CI: 25-36%) higher pathogen burden]. Quantile g-computation revealed PFAS mixtures as a whole were also associated with higher pathogen burdens. Taken together, these results suggest PFAS exposure may increase susceptibility to and foster the clustering of persistent infections, particularly among adolescents. Since persistent infections are important contributors to long-term health, prospective data are needed to confirm these findings.

Keywords: Chemical mixtures; Infectious disease; PFAS; Pathogens.

Figure 1.

Directed Acyclic Graph of Hypothesized Associations between PFAS Exposures and Pathogen Burden

Figure 2.

Adjusted Associations of Individual Serum PFAS Concentrations with Pathogen Burden Note: Adjusted for age (years, restricted cubic spline), race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American, other Hispanic, other race), sex (male, female), the ratio of family income to the federal poverty threshold (unitless, restricted cubic spline), educational attainment (less than high school diploma, high school diploma, some college, college graduate), serum cotinine concentrations (ng/mL, restricted cubic spline), BMI (kg/m², restricted cubic spline) with an offset term for the (log-transformed) number of pathogens to which IgG antibodies were tested.

Figure 3.

Correlations between Serum PFAS Concentrations and Quantile G-Computation Weights in Relation to Pathogen Burden