Integrating contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies: An observational and genomic study
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eLife assessment
This paper presents an analysis of both contact tracing and whole-genome sequence data to track the elimination of dog-mediated rabies in Pemba Island, Tanzania. The work is a valuable contribution to the literature as it will have practical implications for the elimination of dog-mediated rabies in other regions/contexts. The main claims made are largely supported, but the strength of evidence for the cost-effectiveness is limited.
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Abstract
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 to 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 10-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 and SE0421.
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eLife assessment
This paper presents an analysis of both contact tracing and whole-genome sequence data to track the elimination of dog-mediated rabies in Pemba Island, Tanzania. The work is a valuable contribution to the literature as it will have practical implications for the elimination of dog-mediated rabies in other regions/contexts. The main claims made are largely supported, but the strength of evidence for the cost-effectiveness is limited.
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Reviewer #1 (Public Review):
In this work, the authors set out to use contact tracing and whole-genome sequencing to track the elimination of dog-mediated rabies in Pemba island, Tanzania. A major strength is the use of multiple data types in the analysis. A major limitation is the rudimentary health economics approach to make claims about the cost-effectiveness of different approaches. The work will likely have an impact on influencing the practical policies that can be implemented to target the elimination of dog-mediated rabies in other regions/contexts.
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Reviewer #2 (Public Review):
In this paper, the authors illustrate how a One Health approach can strengthen our understanding of the dynamics of the spread and the control of rabies. This is done by analyzing multiple epidemiological and sequence data from both dogs and humans, on the island of Pemba. The joint analyses of these data make it possible to reconstruct the history of rabies introduction and circulation on the island and to quantify the impact of different control measures in particular the cost per death averted.
Data documenting rabies epidemics tend to be rare and of limited quality so the effort to collect these data and analyze them with state-of-the-art statistical techniques should be saluted.
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Reviewer #3 (Public Review):
In the proposed paper, the authors use a combination of case data and genetic data to characterise the impact of a dog vaccine campaign on rabies transmission on Pemba island. This represents an impressive set of data to answer key questions linked to rabies control. It is rare to see a combination of detailed genetic and epidemiology data from the same disease system. Overall, I thought it was an impressive paper. My only major concerns were with the phylogenetic analyses.
The phylogenetic analyses were difficult to understand. The authors use a phylogenetic framework to estimate the underlying number of rabid dogs per outbreak (171 in the first outbreak and 140 in the second one), but it was unclear to me where the information was coming from. From the supplementary material, it seems the authors build …
Reviewer #3 (Public Review):
In the proposed paper, the authors use a combination of case data and genetic data to characterise the impact of a dog vaccine campaign on rabies transmission on Pemba island. This represents an impressive set of data to answer key questions linked to rabies control. It is rare to see a combination of detailed genetic and epidemiology data from the same disease system. Overall, I thought it was an impressive paper. My only major concerns were with the phylogenetic analyses.
The phylogenetic analyses were difficult to understand. The authors use a phylogenetic framework to estimate the underlying number of rabid dogs per outbreak (171 in the first outbreak and 140 in the second one), but it was unclear to me where the information was coming from. From the supplementary material, it seems the authors build transmission trees consistent with the phylogenies. However, these are reliant on (a) a serial interval and (b) a dispersal kernel. There is no reference as to what serial interval distribution was used and how it was calculated. Similarly, there is no information on the dispersal kernel, including what data was used to fit it. I suspect that the serial interval for rabies (and probably the dispersal kernel) has a long tail, which would lead to substantial uncertainty in the transmission chains, however, I could not see uncertainty in the outbreak sizes.
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