Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: an observational and genomic study
- Ifakara Health Institute, United Republic of Tanzania
- University of Glasgow, United Kingdom
- Princeton University, United States
- University of Nairobi, Kenya
- College of the Atlantic, United States
- Animal and Plant Health Agency, United Kingdom
- Sokoine University of Agriculture, United Republic of Tanzania
- University of Surrey, United Kingdom
- Ministry of Health and Social Welfare, United Republic of Tanzania
- Ministry of Livestock Development and Fisheries, United Republic of Tanzania
- Ministry of Health, Community Development, Gender, Elderly and Children, United Republic of Tanzania
- Nelson Mandela African Institution of Science and Technology, United Republic of Tanzania
- Tanzania Veterinary Laboratory Agency, United Republic of Tanzania
- University of Dar es Salaam, United Republic of Tanzania
- 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.
Article and author information
Author details
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
- 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
- Preprint posted: November 29, 2022 (view preprint)
- Received: November 30, 2022
- Accepted: May 24, 2023
- Accepted Manuscript published: May 25, 2023 (version 1)
- 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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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
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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