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

  1. Max T Eyre  Is a corresponding author
  2. Fábio N Souza
  3. Ticiana SA Carvalho-Pereira
  4. Nivison Nery Jnr
  5. Daiana de Oliveira
  6. Jaqueline S Cruz
  7. Gielson A Sacramento
  8. Hussein Khalil
  9. Elsio A Wunder Jnr
  10. Kathryn P Hacker
  11. José E Hagan
  12. James E Childs
  13. Mitermayer G Reis
  14. Mike Begon
  15. Peter J Diggle
  16. Albert I Ko
  17. Emanuele Giorgi
  18. Federico Costa
  1. Lancaster University, United Kingdom
  2. Federal University of Bahia, Brazil
  3. Swedish University of Agricultural Sciences, Sweden
  4. Yale School of Public Health, United States
  5. University of Pennsylvania, United States
  6. World Health Organization - Denmark, Denmark
  7. 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

  1. Max T Eyre

    Centre for Health Informatics, Computing, and Statistics, Lancaster University, Lancaster, United Kingdom
    For correspondence
    maxeyre3@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9847-8632
  2. Fábio N Souza

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3542-8918
  3. Ticiana SA Carvalho-Pereira

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2370-2198
  4. Nivison Nery Jnr

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
  5. Daiana de Oliveira

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
  6. Jaqueline S Cruz

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
  7. Gielson A Sacramento

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
  8. Hussein Khalil

    Swedish University of Agricultural Sciences, Umeå, Sweden
    Competing interests
    No competing interests declared.
  9. Elsio A Wunder Jnr

    Department of Epidemiology of Microbial Disease, Yale School of Public Health, New Haven, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5239-8511
  10. Kathryn P Hacker

    University of Pennsylvania, Philadelphia, United States
    Competing interests
    No competing interests declared.
  11. José E Hagan

    Regional Office for Europe, World Health Organization - Denmark, Copenhagan, Denmark
    Competing interests
    No competing interests declared.
  12. James E Childs

    Department of Epidemiology of Microbial Disease, Yale School of Public Health, New Haven, United States
    Competing interests
    No competing interests declared.
  13. Mitermayer G Reis

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.
  14. Mike Begon

    Department of Evolution, Ecology and Behaviour, University of Liverpool, Liverpool, United Kingdom
    Competing interests
    No competing interests declared.
  15. Peter J Diggle

    Centre for Health Informatics, Computing, and Statistics, Lancaster University, Lancaster, United Kingdom
    Competing interests
    No competing interests declared.
  16. Albert I Ko

    Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, United States
    Competing interests
    Albert I Ko, has received funding from Serimmune and Zoetis for work related to leptospirosis. AIK also received payment and honoraria from Reckit Global Health Institute for participating in a non-profit panel. AIK received travel support from World Health Organisation and Brazilian Ministry of Health. AIK is listed as co-inventor on an issued patent (US 7,718,183 B2) and pending patent (US 61/951,732) related to leptospirosis vaccines. AIK is also on the following boards: Board of Directors, American Society of Tropical Medicine and Hygiene; Executive Board Member (2009-present), International Leptospirosis Society; Member, Inaugural Expert Panel, Reckitt Global Hygiene Institute; Steering Committee Member, Global Leptospirosis Environmental Action Network (GLEAN), WHO. The author has no other competing interests to declare..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9023-2339
  17. Emanuele Giorgi

    Centre for Health Informatics, Computing, and Statistics, Lancaster University, Lancaster, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0640-181X
  18. Federico Costa

    Institute of Collective Health, Federal University of Bahia, Salvador, Brazil
    Competing interests
    No competing interests declared.

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.

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).

Reviewing Editor

  1. Niel Hens, Hasselt University, Belgium

Publication history

  1. Received: August 17, 2021
  2. Accepted: September 14, 2022
  3. Accepted Manuscript published: September 16, 2022 (version 1)
  4. Accepted Manuscript updated: September 26, 2022 (version 2)

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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  1. Max T Eyre
  2. Fábio N Souza
  3. Ticiana SA Carvalho-Pereira
  4. Nivison Nery Jnr
  5. Daiana de Oliveira
  6. Jaqueline S Cruz
  7. Gielson A Sacramento
  8. Hussein Khalil
  9. Elsio A Wunder Jnr
  10. Kathryn P Hacker
  11. José E Hagan
  12. James E Childs
  13. Mitermayer G Reis
  14. Mike Begon
  15. Peter J Diggle
  16. Albert I Ko
  17. Emanuele Giorgi
  18. Federico Costa
(2022)
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

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