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
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
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- Computational and Systems Biology
- Epidemiology and Global Health
The chemical composition of foods is complex, variable, and dependent on many factors. This has a major impact on nutrition research as it foundationally affects our ability to adequately assess the actual intake of nutrients and other compounds. In spite of this, accurate data on nutrient intake are key for investigating the associations and causal relationships between intake, health, and disease risk at the service of developing evidence-based dietary guidance that enables improvements in population health. Here, we exemplify the importance of this challenge by investigating the impact of food content variability on nutrition research using three bioactives as model: flavan-3-ols, (–)-epicatechin, and nitrate. Our results show that common approaches aimed at addressing the high compositional variability of even the same foods impede the accurate assessment of nutrient intake generally. This suggests that the results of many nutrition studies using food composition data are potentially unreliable and carry greater limitations than commonly appreciated, consequently resulting in dietary recommendations with significant limitations and unreliable impact on public health. Thus, current challenges related to nutrient intake assessments need to be addressed and mitigated by the development of improved dietary assessment methods involving the use of nutritional biomarkers.
