Abstract
BACKGROUND: Leprosy remains a persistent public health challenge, where human-to-human transmission of Mycobacterium leprae via respiratory droplets is well established. In the tropical Americas, growing evidence implicates armadillos as important zoonotic reservoirs, particularly through direct contact during hunting and handling. However, such transmission has so far been considered rare and highly localised. This study provides a comprehensive spatial analysis of the role of armadillo hunting in human leprosy transmission, quantifying its contribution to disease prevalence and identifying geographic hotspots where interventions could be most effective. METHODS: Using Brazil's 326,001 reported leprosy cases from 2013 to 2022, we applied a pathogeographical approach to explore transmission dynamics. We compiled data on 554 hunted armadillos across 175 municipalities and M. leprae prevalence in 376 armadillo individuals from 97 municipalities (mean prevalence = 38.5%). These were used to build spatial models assessing hunting-related infection risk and integrated as a variable into a generalised linear model alongside socioeconomic, climatic, and environmental predictors to evaluate their effects on human leprosy prevalence. RESULTS: Key predictors of armadillo hunting included higher population density (P < 0.001) and firearm availability (P < 0.01). Infection in armadillos was negatively correlated with native habitat coverage (coefficient: - 2.28; P < 0.001), suggesting that environmental degradation can amplify infection risk. The armadillo-hunting infection risk variable-generated by combining armadillo hunting and infection favourability models-emerged as the second strongest predictor of human leprosy prevalence (coefficient: 1.69; P < 0.001), accounting for ~ 25% of cases nationally and around 40% in deforestation hotspots. Additional positive predictors included greater precipitation seasonality (coefficient: 0.82; P < 0.001) and malnutrition (coefficient: 0.01; P < 0.001), while higher population density (coefficient: - 0.64; P < 0.001), natural habitat coverage (coefficient: - 0.50; P < 0.001) and socioeconomic status (coefficient: - 0.47; P = 0.013) were linked to reduced disease prevalence. CONCLUSIONS: Armadillo hunting seems to play a more significant role in human leprosy transmission than previously recognised. To address this overlooked pathway, targeted interventions should focus on reducing unsafe and illegal hunting, improving communication around zoonotic risks, strengthening disease surveillance in high-risk areas, and conducting genetic studies to confirm wildlife-to-human transmission. Our findings highlight the importance of incorporating wildlife-associated transmission pathways into strategies to reduce disease prevalence and mitigate future outbreaks in tropical regions facing rapid environmental change and persistent poverty.