Local heterogeneity in Lassa fever serology in rural Nigeria: Implications for vaccine trial site selection

INTRODUCTION: Lassa virus (LASV) causes significant morbidity in West Africa, yet vaccine trial planning is hampered by a lack of high-resolution, community-level seroprevalence data. We aimed to characterize the fine-scale spatial and demographic heterogeneity of LASV exposure in rural Nigeria to inform site selection strategies. METHODS: We conducted a cross-sectional serosurvey across nine villages in three Nigerian states (Benue, Ebonyi, and Cross River). We recruited 1,874 individuals and tested for LASV IgG using the highly specific Panadea LASV IgG ELISA. We employed Bayesian hierarchical models to estimate seroprevalence and investigated 21 pre-specified demographic, environmental, and behavioral risk factors for association with seropositivity. Village-specific transmission dynamics were explored using Bayesian generalized additive models for age-stratified seroprevalence. RESULTS: The overall model-based IgG seroprevalence was 3.2% (95% CrI: 2.5-4.0%). We observed marked fine-scale heterogeneity, with village-level estimates ranging from 0.8% to 6.5%. Age-seroprevalence curves suggested? divergent transmission dynamics, ranging from cumulative endemic exposure to recent focal outbreaks in younger cohorts. Likely constrained by low overall prevalence and high exposure ubiquity, univariable analyses detected no strong or consistent associations between seropositivity and the 21 pre-specified risk factors, including rodent consumption and agricultural practices. No significant village-wide spatial clustering of seropositive households was observed via Local Getis-Ord (Gi*). DISCUSSION: LASV exposure in rural Nigeria is characterized by low overall prevalence punctuated by significant hyper-local variation. The lack of consistent individual-level risk factors and the divergent age-exposure profiles suggest that risk may be influenced by stochastic, localized ecological drivers or obscured by the temporal misalignment of cross-sectional surveys. Vaccine trial site selection must move beyond regional incidence data to incorporate interdisciplinary, One Health metrics including high-resolution human serosurveillance and longitudinal reservoir monitoring to identify active transmission hotspots.