Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: an eco-epidemiological community-based cohort study in Brazil

Background: Zoonotic spillover from animal reservoirs is responsible for a significant global public health burden, but the processes that promote spillover events are poorly understood in complex urban settings. Endemic transmission of Leptospira, the agent of leptospirosis, in marginalised urban communities occurs through human exposure to an environment contaminated by bacteria shed in the urine of the rat reservoir. However, it is unclear to what extent transmission is driven by variation in the distribution of rats or by the dispersal of bacteria in rainwater runoff and overflow from open sewer systems. Methods: We conducted an eco-epidemiological study in a high-risk community in Salvador, Brazil, by prospectively following a cohort of 1,401 residents to ascertain serological evidence for leptospiral infections. A concurrent rat ecology study was used to collect information on the fine-scale spatial distribution of rattiness, our proxy for rat abundance and exposure of interest. We developed and applied a novel geostatistical framework for joint spatial modelling of multiple indices of disease reservoir abundance and human infection risk. Results: The estimated infection rate was 51.4 (95%CI 40.4, 64.2) infections per 1,000 follow-up events. Infection risk increased with age until 30 years of age and was associated with male gender. Rattiness was positively associated with infection risk for residents across the entire study area, but this effect was stronger in higher elevation areas (OR 3.27 95%CI 1.68, 19.07) than in lower elevation areas (OR 1.14 95%CI 1.05, 1.53). Conclusions: These findings suggest that, while frequent flooding events may disperse bacteria in regions of low elevation, environmental risk in higher elevation areas is more localised and directly driven by the distribution of local rat populations. The modelling framework developed may have broad applications in delineating complex animal-environment-human interactions during zoonotic spillover and identifying opportunities for public health intervention.Funding: This work was supported by the Oswaldo Cruz Foundation and Secretariat of Health Surveillance, Brazilian Ministry of Health, the National Institutes of Health of the United States (grant numbers F31 AI114245, R01 AI052473, U01 AI088752, R01 TW009504 and R25 TW009338); the Wellcome Trust (102330/Z/13/Z), and by the Fundacao de Amparo a Pesquisa do Estado da Bahia (FAPESB/JCB0020/2016). M.T.E is supported by an MRC doctorate studentship. F.N.S. participated in this study under a FAPESB doctorate scholarship.