Scrub typhus is a mite-borne infection, largely affecting rural populations in many parts of Asia. This cohort study explored socio-demographic, behavioural, and spatial risk factors at different levels of endemicity. 2206 rural residents from 37 villages in Tamil Nadu, South India, underwent a questionnaire survey and blood sampling at baseline and annually over 2 years to detect sero-conversion. Satellite images were used for visual land use classification. Local sero-prevalence was estimated using 5602 baseline blood samples.

Two hundred and seventy cases of seroconversions occurred during 3629 person-years (incidence rate 78/1000, 95%CI 67, 91). Older age was associated with scrub typhus in crude but not in multivariable analysis adjusting for socio-economic factors. By contrast, the increased risk in females compared to males (RR 1.4) was unaffected by adjusting for confounders. In multivariable analysis, agricultural and related outdoor activities were only weakly associated with scrub typhus. However, agricultural activities were strongly associated with scrub typhus if local sero-prevalence was low, but not if it was high. Females were at a higher risk than males in high-prevalence areas but not in low-prevalence areas. To conclude, agricultural activities were not strongly associated with scrub typhus. Transmission within human settlements may predominate in highly endemic settings.