Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: an eco-epidemiological community-based cohort study in Brazil
- Lancaster University, United Kingdom
- Federal University of Bahia, Brazil
- Swedish University of Agricultural Sciences, Sweden
- Yale School of Public Health, United States
- University of Pennsylvania, United States
- World Health Organization - Denmark, Denmark
- University of Liverpool, United Kingdom
Abstract
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 37 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 Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB/JCB0020/2016). MTE was supported by a Medical Research UK doctorate studentship. FBS participated in this study under a FAPESB doctorate scholarship.
Data availability
Rat and human data analysed in this study have been deposited in OSF (https://doi.org/10.17605/OSF.IO/AQZ2Y). However, household coordinates and valley ID have been removed from the human data to ensure participant anonymity. Modelling functions, R scripts and metadata for analyses in this manuscript are publicly available at https://github.com/maxeyre/Rattiness-infection-framework.
Article and author information
Author details
Ticiana SA Carvalho-Pereira
Elsio A Wunder Jnr
Funding
National Institutes of Health (F31 AI114245)
- Albert I Ko
- Federico Costa
National Institutes of Health (R01 AI052473)
- Albert I Ko
- Federico Costa
National Institutes of Health (U01 AI088752)
- Albert I Ko
- Federico Costa
National Institutes of Health (R01 TW009504)
- Albert I Ko
- Federico Costa
National Institutes of Health (R25 TW009338)
- Albert I Ko
- Federico Costa
Medical Research Council (964635)
- Max T Eyre
Wellcome Trust (102330/Z/13/Z)
- Nivison Nery Jnr
- Albert I Ko
- Federico Costa
Fundação Oswaldo Cruz
- Federico Costa
Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB/JCB0020/2016)
- Fábio N Souza
- Federico Costa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Niel Hens, Hasselt University, Belgium
Ethics
Animal experimentation: For the rats captured in the rat ecology study, the ethics committee for the use of animals from the Oswaldo Cruz Foundation, Salvador, Brazil, approved the protocols used (protocol number 003/2012), which adhered to the guidelines of the American Society of Mammalogists for the use of wild mammals in research [48] and the guidelines of the American Veterinary Medical Association for the euthanasia of animals [49]. These protocols were also approved by Yale University's Institutional Animal Care and Use Committee (IACUC), New Haven, Connecticut (protocol number 2012-11498).
Human subjects: Participants were enrolled according to written informed consent procedures approved by the Institutional Review Boards of the Oswaldo Cruz Foundation and Brazilian National Commission for Ethics in Research, Brazilian Ministry of Health (CAAE: 01877912.8.0000.0040) and Yale University School of Public Health (HIC 1006006956).
Version history
- Received: August 17, 2021
- Preprint posted: September 22, 2021 (view preprint)
- Accepted: September 14, 2022
- Accepted Manuscript published: September 16, 2022 (version 1)
- Accepted Manuscript updated: September 26, 2022 (version 2)
- Version of Record published: October 13, 2022 (version 3)
- Version of Record updated: October 18, 2022 (version 4)
Copyright
© 2022, Eyre et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Linking rattiness, geography and environmental degradation to spillover Leptospira infections in marginalised urban settings: an eco-epidemiological community-based cohort study in Brazil
eLife 11:e73120.
https://doi.org/10.7554/eLife.73120
Further reading
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- Epidemiology and Global Health
Background:
Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality.
Methods:
We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow-up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors.
Results:
Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15–38%) higher total mortality, 14% (95% CI, 0–31%) higher cancer mortality, and 31% (95% CI, 10–55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects.
Conclusions:
Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality.
Funding:
Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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