Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: an observational and genomic study

  1. Kennedy Lushasi
  2. Kirstyn Brunker
  3. Malavika Rajeev
  4. Elaine A Ferguson
  5. Gurdeep Jaswant
  6. Laurie Louise Baker
  7. Roman Biek
  8. Joel Changalucha
  9. Sarah Cleaveland
  10. Anna Czupryna
  11. Anthony R Fooks
  12. Nicodemus J Govella
  13. Daniel T Haydon
  14. Paul CD Johnson
  15. Rudovick Kazwala
  16. Tiziana Lembo
  17. Denise Marston
  18. Msanif Masoud
  19. Matthew Maziku
  20. Eberhard Mbunda
  21. Geofrey Mchau
  22. Ally Z Mohamed
  23. Emmanuel Mpolya
  24. Chanasa Ngeleja
  25. Kija Ng'habi
  26. Hezron Nonga
  27. Kassim Omar
  28. Kristyna Rysava
  29. Maganga Sambo
  30. Lwitiko Sikana
  31. Rachel Steenson
  32. Katie Hampson  Is a corresponding author
  1. Ifakara Health Institute, United Republic of Tanzania
  2. University of Glasgow, United Kingdom
  3. Princeton University, United States
  4. University of Nairobi, Kenya
  5. College of the Atlantic, United States
  6. Animal and Plant Health Agency, United Kingdom
  7. Sokoine University of Agriculture, United Republic of Tanzania
  8. University of Surrey, United Kingdom
  9. Ministry of Health and Social Welfare, United Republic of Tanzania
  10. Ministry of Livestock Development and Fisheries, United Republic of Tanzania
  11. Ministry of Health, Community Development, Gender, Elderly and Children, United Republic of Tanzania
  12. Nelson Mandela African Institution of Science and Technology, United Republic of Tanzania
  13. Tanzania Veterinary Laboratory Agency, United Republic of Tanzania
  14. University of Dar es Salaam, United Republic of Tanzania
  15. University of Warwick, United Kingdom

Abstract

Background:

Dog-mediated rabies is endemic across Africa causing thousands of human deaths annually. A One Health approach to rabies is advocated, comprising emergency post-exposure vaccination of bite victims and mass dog vaccination to break the transmission cycle. However, the impacts and cost-effectiveness of these components are difficult to disentangle.

Methods:

We combined contact tracing with whole-genome sequencing to track rabies transmission in the animal reservoir and spillover risk to humans from 2010-2020, investigating how the components of a One Health approach reduced the disease burden and eliminated rabies from Pemba Island, Tanzania. With the resulting high-resolution spatiotemporal and genomic data we inferred transmission chains and estimated case detection. Using a decision tree model we quantified the public health burden and evaluated the impact and cost-effectiveness of interventions over a ten-year time horizon.

Results:

We resolved five transmission chains co-circulating on Pemba from 2010 that were all eliminated by May 2014. During this period, rabid dogs, human rabies exposures and deaths all progressively declined following initiation and improved implementation of annual islandwide dog vaccination. We identified two introductions to Pemba in late 2016 that seeded re-emergence after dog vaccination had lapsed. The ensuing outbreak was eliminated in October 2018 through reinstated islandwide dog vaccination. While post-exposure vaccines were projected to be highly cost-effective ($256 per death averted), only dog vaccination interrupts transmission. A combined One Health approach of routine annual dog vaccination together with free post-exposure vaccines for bite victims, rapidly eliminates rabies, is highly cost-effective ($1657 per death averted) and by maintaining rabies freedom prevents over 30 families from suffering traumatic rabid dog bites annually on Pemba island.

Conclusions:

A One Health approach underpinned by dog vaccination is an efficient, cost-effective, equitable and feasible approach to rabies elimination, but needs scaling up across connected populations to sustain the benefits of elimination, as seen on Pemba, and for similar progress to be achieved elsewhere.

Funding:

Wellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, the Department of Health and Human Services of the National Institutes of Health [R01AI141712] and the DELTAS Africa Initiative [Afrique One-ASPIRE/DEL-15-008] comprising a donor consortium of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA), the New Partnership for Africa's Development Planning and Coordinating (NEPAD) Agency, Wellcome [107753/A/15/Z], Royal Society of Tropical Medicine and Hygiene Small Grant 2017 [GR000892] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation [OPP49679]. Whole-genome sequencing was partially supported from APHA by funding from the UK Department for Environment, Food and Rural Affairs (Defra), Scottish government and Welsh government under projects SEV3500 & SE0421.

Data availability

Code to reproduce the analyses together with deidentified data are available from our public Github repository https://github.com/boydorr/PembaRabies and archived on Zenodo DOI: 10.5281/zenodo.7922464. Sequences are deposited on Genbank.

The following data sets were generated

Article and author information

Author details

  1. Kennedy Lushasi

    Environmental Health and Ecological Sciences Department, Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2060-4202
  2. Kirstyn Brunker

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Malavika Rajeev

    Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Elaine A Ferguson

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2010-765X
  5. Gurdeep Jaswant

    University of Nairobi, Nairobi, Kenya
    Competing interests
    The authors declare that no competing interests exist.
  6. Laurie Louise Baker

    College of the Atlantic, Bar Barbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Roman Biek

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3471-5357
  8. Joel Changalucha

    Environmental Health and Ecological Sciences Department, Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  9. Sarah Cleaveland

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Anna Czupryna

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Anthony R Fooks

    Animal and Plant Health Agency, Weybridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Nicodemus J Govella

    Environmental Health and Ecological Sciences Department, Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  13. Daniel T Haydon

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Paul CD Johnson

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6663-7520
  15. Rudovick Kazwala

    Department of Veterinary Medicine and Public Health, Sokoine University of Agriculture, Morogoro, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  16. Tiziana Lembo

    Boyd Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Denise Marston

    Department of Comparative Biomedical Sciences, University of Surrey, Guilford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  18. Msanif Masoud

    Ministry of Health and Social Welfare, Zanzibar, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  19. Matthew Maziku

    Ministry of Livestock Development and Fisheries, Dodoma, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  20. Eberhard Mbunda

    Ministry of Livestock Development and Fisheries, Dodoma, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  21. Geofrey Mchau

    Department of Epidemiology, Ministry of Health, Community Development, Gender, Elderly and Children, Dodoma, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  22. Ally Z Mohamed

    Ministry of Livestock Development and Fisheries, Zanzibar, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  23. Emmanuel Mpolya

    Department of Global Health and Biomedical Sciences, Nelson Mandela African Institution of Science and Technology, Arusha, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6210-9445
  24. Chanasa Ngeleja

    Tanzania Veterinary Laboratory Agency, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  25. Kija Ng'habi

    Mbeya College of Health and Allied Sciences, University of Dar es Salaam, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  26. Hezron Nonga

    Ministry of Livestock Development and Fisheries, Dodoma, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  27. Kassim Omar

    Ministry of Livestock Development and Fisheries, Zanzibar, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  28. Kristyna Rysava

    University of Warwick, Warwick, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  29. Maganga Sambo

    Environmental Health and Ecological Sciences Department, Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  30. Lwitiko Sikana

    Environmental Health and Ecological Sciences Department, Ifakara Health Institute, Dar es Salaam, United Republic of Tanzania
    Competing interests
    The authors declare that no competing interests exist.
  31. Rachel Steenson

    Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  32. Katie Hampson

    Orr Centre for Population and Ecosystem Health, University of Glasgow, Glasgow, United Kingdom
    For correspondence
    katie.hampson@glasgow.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5392-6884

Funding

Wellcome Trust (207569/Z/17/Z,095787/Z/11/Z)

  • Katie Hampson

Wellcome Trust (103270/Z/13/Z)

  • Kennedy Lushasi

UBS Optimus Foundation (NA)

  • Tiziana Lembo

National Institutes of Health (Department of Health and Human Services (R01AI141712)

  • Katie Hampson

DELTAS Africa Initiative (Afrique One-ASPIRE/DEL-15-008)

  • Kennedy Lushasi

Bill and Melinda Gates Foundation (OPP49679)

  • Sarah Cleaveland

UK Department for Environment, Food and Rural Affairs , Scottish government and Welsh government (SEV3500 & SE0421)

  • Anthony R Fooks

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jennifer Flegg, The University of Melbourne, Australia

Ethics

Human subjects: The study was approved by the Zanzibar Medical Research and Ethics Committee (ZAMREC/0001/JULY/014), the Medical Research Coordinating Committee of the National Institute for Medical Research of Tanzania (NIMR/HQ/R.8a/vol.IX/2788), the Ministry of Regional Administration and Local Government (AB.81/288/01), and Ifakara Health Institute Institutional Review Board (IHI/IRB/No:22-2014).

Version history

  1. Preprint posted: November 29, 2022 (view preprint)
  2. Received: November 30, 2022
  3. Accepted: May 24, 2023
  4. Accepted Manuscript published: May 25, 2023 (version 1)
  5. Version of Record published: June 27, 2023 (version 2)

Copyright

© 2023, Lushasi 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. Kennedy Lushasi
  2. Kirstyn Brunker
  3. Malavika Rajeev
  4. Elaine A Ferguson
  5. Gurdeep Jaswant
  6. Laurie Louise Baker
  7. Roman Biek
  8. Joel Changalucha
  9. Sarah Cleaveland
  10. Anna Czupryna
  11. Anthony R Fooks
  12. Nicodemus J Govella
  13. Daniel T Haydon
  14. Paul CD Johnson
  15. Rudovick Kazwala
  16. Tiziana Lembo
  17. Denise Marston
  18. Msanif Masoud
  19. Matthew Maziku
  20. Eberhard Mbunda
  21. Geofrey Mchau
  22. Ally Z Mohamed
  23. Emmanuel Mpolya
  24. Chanasa Ngeleja
  25. Kija Ng'habi
  26. Hezron Nonga
  27. Kassim Omar
  28. Kristyna Rysava
  29. Maganga Sambo
  30. Lwitiko Sikana
  31. Rachel Steenson
  32. Katie Hampson
(2023)
Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: an observational and genomic study
eLife 12:e85262.
https://doi.org/10.7554/eLife.85262

Share this article

https://doi.org/10.7554/eLife.85262

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