Abstract
BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection is a lifelong sexually transmitted infection with substantial disease and economic burdens. Despite its global impact, key features of its transmission dynamics-including sex-specific biological susceptibility (the inherent likelihood of acquiring infection upon exposure, independent of behavioral factors) and sexual mixing patterns (how individuals form sexual partnerships across age and risk groups)-remain poorly quantified. METHODS: A population-level mathematical model of HSV-2 transmission dynamics was applied to heterosexual transmission in the USA and calibrated to nationally representative data from the National Health and Nutrition Examination Surveys (NHANES) conducted between 1988 and 2016. Bayesian inference was used to estimate: (1) relative biological susceptibility of women compared to men, (2) degree of assortativity in age group mixing, and (3) degree of assortativity in sexual risk behavior group mixing. Assortativity reflects the tendency of individuals to form partnerships with others who share similar characteristics, such as age or level of sexual risk behavior, and was quantified on a scale from 0 (no preferential mixing) to 1 (exclusive within-group mixing). RESULTS: The model demonstrated robust fits to sex-specific, age-specific, and temporal trends in HSV-2 prevalence across NHANES rounds, supporting the validity of the inferred transmission dynamics. Women were estimated to be 7.12 times (95% credible interval (Crl) 4.36-10.17) more biologically susceptible to HSV-2 infection than men, indicating a substantially higher likelihood of acquiring infection upon exposure. The degree of assortativity in age group mixing was high at 0.83 (95% Crl 0.75-0.88), indicating that most transmission occurs between individuals of similar age. In contrast, assortativity in sexual risk behavior group mixing was moderate at 0.49 (95% Crl 0.43-0.55), indicating that transmission frequently occurs across different risk groups rather than being confined within the same group. CONCLUSIONS: Women are much more biologically susceptible to HSV-2 infection than men. HSV-2 transmission mostly occurs within similar age groups but often crosses different sexual risk groups, reflecting strong age-assortative and moderate risk-assortative mixing patterns.