An age-structured mathematical model of tetanus epidemiology, immunity, and vaccination across the life course

Tetanus remains a significant public health concern despite substantial reductions in incidence and mortality following the widespread introduction of tetanus-toxoid-containing vaccines (TTCVs). Because immunity is acquired only through vaccination and wanes over time, the World Health Organization recommends three booster doses throughout childhood and adolescence in addition to the three-dose infant primary series. However, few mathematical models explicitly represent the cumulative, dose-dependent nature of tetanus immunity needed to evaluate alternative vaccination strategies. We developed a novel age-structured model of tetanus epidemiology, immunity, and vaccination to address this gap.

We developed a deterministic compartmental model stratified by age, vaccination history, and immunity status. The model incorporates environmental exposure, neonatal and non-neonatal tetanus, routine infant vaccination, booster doses, maternal immunization, and waning immunity. Unlike previous tetanus models, each TTCV dose is represented explicitly, allowing protection, waning, and booster responses to vary according to vaccination history. Model parameters were informed by published literature and expert consultation. Sensitivity analyses were conducted using Latin hypercube sampling and partial rank correlation coefficients, and model outputs were compared with published seroprevalence studies.

The model reproduced expected patterns of vaccine-derived immunity and waning described in the literature and generated population protection estimates consistent with seroprevalence data from settings with different vaccination schedules. Sensitivity analyses identified the duration of vaccine-derived protection as a primary source of uncertainty, with vaccine effectiveness also substantially influencing population immunity. The framework successfully captured heterogeneous immunity profiles by age and vaccination history and the cumulative effects of primary series, booster doses, and maternal vaccination.

This model provides a novel framework for representing cumulative TTCV-derived immunity across the life course. By explicitly tracking dose-specific protection and waning, it enables the evaluation of booster-dose strategies and maternal immunization programs and provides a platform for informing evidence-based tetanus vaccination policy.