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BackgroundDog-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.MethodsWe 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, estimated case detection and quantified the public health burden to evaluate these interventions.ResultsWe 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 highly cost-effective ($405 per death averted), their accessibility was limited and only dog vaccination interrupted transmission. A combined One Health approach rapidly eliminated rabies, was highly cost-effective ($1865 per death averted) and saved 20-120 families from rabid dog bites annually.ConclusionsA 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.FundingWellcome [207569/Z/17/Z, 095787/Z/11/Z, 103270/Z/13/Z], the UBS Optimus Foundation, 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] and the UK government. The rabies elimination demonstration project from 2010-2015 was supported by the Bill & Melinda Gates Foundation (OPP49679) and whole-genome sequencing was partially supported at APHA by Defra grant SE0421.

1. Understanding the role of different species in the transmission of multi-host pathogens, such as rabies virus, is vital for effective control strategies. Across most of sub-Saharan Africa domestic dogs Canis familiaris are considered the reservoir for rabies, but the role of wildlife has been long debated. Here we explore the multi-host transmission dynamics of rabies across south-east Tanzania. 2. Between January 2011 and July 2019, data on probable rabies cases were collected in the regions of Lindi and Mtwara. Hospital records of animal-bite patients presenting to healthcare facilities were used as sentinels for animal contact tracing. The timing, location and species of probable rabid animals were used to reconstruct transmission trees to infer who infected whom and the relative frequencies of within- and between-species transmission. 3. During the study, 688 probable human rabies exposures were identified, resulting in 47 deaths. Of these exposures, 389 were from domestic dogs (56.5%) and 262 from jackals (38.1%). Over the same period, 549 probable animal rabies cases were traced: 303 in domestic dogs (55.2%) and 221 in jackals (40.3%), with the remainder in domestic cats and other wildlife species. 4. Although dog-to-dog transmission was most commonly inferred (40.5% of transmission events), a third of inferred events involved wildlife-to-wildlife transmission (32.6%), and evidence suggested some sustained transmission chains within jackal populations. 5. A steady decline in probable rabies cases in both humans and animals coincided with the implementation of widespread domestic dog vaccination during the first 6 years of the study. Following the lapse of this program, dog rabies cases began to increase in one of the northernmost districts. 6. Synthesis and applications. In south-east Tanzania, despite a relatively high incidence of rabies in wildlife and evidence of wildlife-to-wildlife transmission, domestic dogs remain essential to the reservoir of infection. Continued dog vaccination alongside improved surveillance would allow a fuller understanding of the role of wildlife in maintaining transmission in this area. Nonetheless, dog vaccination clearly suppressed rabies in both domestic dog and wildlife populations, reducing both public health and conservation risks and, if sustained, has potential to eliminate rabies from this region.

Background: Every year at least 59,000 people are estimated to die from rabies and more than 10 million are treated with post-exposure prophylaxis (PEP). Over 99% of human rabies deaths occur in developing countries due to bites from domestic dogs. Large-scale mass dog vaccination programs can control dog rabies and, if sustained, can eliminate dog-mediated rabies. However, there has been very little investment in mass dog vaccination against rabies in sub-Saharan Africa, largely due to limited human and financial resources. To overcome this limitation, we piloted the delivery of synchronized dog vaccinations using a temporary workforce of university students. Fifty university students from Sokoine University of Agriculture and Muhimbili University of Health and Allied Sciences were selected to deliver dog vaccinations throughout the Kisarawe district in Tanzania in May 2021. We analysed the vaccination coverage achieved and the cost per dog vaccinated in delivering dog vaccinations using the university students compared to the traditional delivery. Results: A total of 1,457 dogs and 242 cats were vaccinated across 48 villages in the Kisarawe district of Tanzania over the course of five days. The overall cost in delivering mass dog vaccinations was estimated at US$ 28,990 equating to approximately US$19.90 per vaccinated dog. Post-vaccination transects were conducted in all 48 villages where dog vaccinations were implemented, counting 387 dogs. Of these, 54% dogs (N=210) were vaccinated against rabies, 67% (N=258) were free-roaming dogs and 72% of dogs encountered were adult (N=277). The overall district-level mean vaccination coverage was estimated to be 54.3% (CI 49.3% - 59.6). Conclusions: We demonstrated that using university students as a One Health workforce is effective in accelerating the countries’ efforts to meet the global target of eliminating dog-mediated human rabies by 2030.

Highlights • Prompt post-exposure vaccination is extremely effective in preventing human rabies. • Intradermal post-exposure vaccination is easily adopted by health workers in Tanzania. • High costs of PEP to government affect the supply chain and limit its availability. • Limited PEP supply results in higher out-of-pocket payments and increased risks. • Investment to facilitate free PEP provision would reduce rabies deaths., Background Rabies is preventable through prompt administration of post-exposure prophylaxis (PEP) to exposed persons, but PEP access is limited in many rabies-endemic countries. We investigated how access to PEP can be improved to better prevent human rabies. Methods Using data from different settings in Tanzania, including contact tracing (2,367 probable rabies exposures identified) and large-scale mobile phone-based surveillance (24,999 patient records), we estimated the incidence of rabies exposures and bite-injuries, and examined health seeking and health outcomes in relation to PEP access. We used surveys and qualitative interviews with stakeholders within the health system to further characterise PEP supply and triangulate these findings. Results Incidence of bite-injury patients was related to dog population sizes, with higher incidence in districts with lower human:dog ratios and urban centres. A substantial percentage (25%) of probable rabies exposures did not seek care due to costs and limited appreciation of risk. Upon seeking care a further 15% of probable rabies exposed persons did not obtain PEP due to shortages, cost barriers or misadvice. Of those that initiated PEP, 46% did not complete the course. If no PEP was administered, the risk of developing rabies following a probable rabies exposure was high (0.165), with bites to the head carrying most risk. Decentralized and free PEP increased the probability that patients received PEP and reduced delays in initiating PEP. No major difficulties were encountered by health workers whilst switching to dose-sparing ID administration of PEP. Health infrastructure also includes sufficient cold chain capacity to support improved PEP provision. However, high costs to governments and patients currently limits the supply chain and PEP access. The cost barrier was exacerbated by decentralization of budgets, with priority given to purchase of cheaper medicines for other conditions. Reactive procurement resulted in limited and unresponsive PEP supply, increasing costs and risks to bite victims. Conclusion PEP access could be improved and rabies deaths reduced through ring-fenced procurement, switching to dose-sparing ID regimens and free provision of PEP.

Background The human resource gap in veterinary sectors, particularly in low-income countries, imposes limitations on the delivery of animal healthcare in hard-to-reach populations. Lay animal health workers have been deployed in these settings to fill the gap though there are mixed views about the benefits of doing this and whether they can deliver services safely. We mapped evidence on the nature and extent of roles assigned to lay animal vaccinators, and identified lessons useful for their future deployment. Methodology/Principal findings Following the PRISMA Extension for Scoping Reviews guidelines, we searched seven bibliographic databases for articles published between 1980 and 2021, with the search terms lay OR community-based OR volunteer AND "animal health worker" OR vaccinator*, and applied an a priori exclusion criteria to select studies. From 30 identified studies, lay vaccinators were used by non-government developmental (n = 12, 40%), research (n = 10, 33%) and government (n = 5, 17%) programmes to vaccinate domestic animals. The main reason for using lay vaccinators was to provide access to animal vaccination in the absence of professional veterinarians (n = 12, 40%). Reported positive outcomes of programmes included increased flock and herd sizes and farmer knowledge of best practice (n = 13, 43%); decreased disease transmission, outbreaks and mortality (n = 11, 37%); higher vaccination coverage (10, 33%); non-inferior seroconversion and birth rates among vaccinated herds (n = 3, 10%). The most frequently reported facilitating factor of lay vaccinator programmes was community participation (n = 14, 47%), whilst opposition from professional veterinarians (n = 8, 27%), stakeholders seeking financial gains to detriment of programmes goals (n = 8, 27%) and programming issues (n = 8, 27%) were the most frequently reported barriers. No study reported on cost-effectiveness and we found no record from a low and middle-income country of lay vaccinator programmes being integrated into national veterinary services. Conclusion Although the majority of included studies reported more benefits and positive perceptions of lay vaccinator programmes than problems and challenges, regularization will ensure the programmes can be designed and implemented to meet the needs of all stakeholders., Author summary In the absence of professional animal healthcare workers in hard-to-reach settings, lay persons, with limited, non-formal training, have been used to provide animal healthcare services, including vaccination. In spite of the perceived crucial roles lay persons play in the animal health sector, their services are largely unrecognized within official animal healthcare systems. We compiled evidence on how lay persons have been used in animal vaccination programmes and make recommendations regarding how they can be used in more effective ways. We found they were used by both government and non-government institutions to vaccinate different domestic animals and provide regular animal healthcare services. They were mainly used where professional animal healthcare workers are not available or are limited in number. The programmes were more successful where they had the support of the public and institutions, and their outcomes were largely similar to those delivered by professionals. We also found that community participation was an important facilitating factor, whilst the main challenges they faced were opposition from professional veterinarians, financial interests of stakeholders and planning issues. We concluded that lay animal vaccinator programmes could be more beneficial if better regulated.

An increasing number of countries are committing to meet the global target to eliminate human deaths from dog-mediated rabies by 2030. Mass dog vaccination is central to this strategy. To interrupt rabies transmission from dogs to humans, the World Health Organization recommends that vaccination campaigns should be carried out every year in all dog-owning communities vaccinating 70% of their susceptible dogs. Monitoring and evaluation of dog vaccination campaigns are needed to measure progress towards elimination. In this study, we measured the delivery performance of large-scale vaccination campaigns implemented in 25 districts in south-east Tanzania from 2010 until 2017. We used regression modelling to infer the factors associated with, and potentially influencing the successful delivery of vaccination campaigns. During 2010–2017, five rounds of vaccination campaigns were carried out, vaccinating in total 349,513 dogs in 2,066 administrative vaccination units (rural villages or urban wards). Progressively more dogs were vaccinated over the successive campaigns. The campaigns did not reach all vaccination units each year, with only 16–28% of districts achieving 100% campaign completeness (where all units were vaccinated). During 2013–2017 when vaccination coverage was monitored, approximately 20% of vaccination units achieved the recommended 70% coverage, with average coverage around 50%. Campaigns were also not completed at annual intervals, with the longest interval between campaigns being 27 months. Our analysis revealed that districts with higher budgets generally achieved higher completeness, with a twofold difference in district budget increasing the odds of a vaccination unit being reached by a campaign by slightly more than twofold (OR: 2.29; 95% CI: 1.69–3.09). However, higher budgets did not necessarily result in higher coverage within vaccination units that were reached. We recommend national programs regularly monitor and evaluate the performance of their vaccination campaigns, so as to identify factors hindering their effective delivery and to guide remedial action.

Interventions tackling zoonoses require an understanding of healthcare patterns related to both human and animal hosts. The control of dog-mediated rabies is a good example. Despite the availability of effective control measures, 59,000 people die of rabies every year worldwide. In Tanzania, children are most at risk, contributing ~40% of deaths. Mass dog vaccination can break the transmission cycle, but reaching the recommended 70% coverage is challenging where vaccination depends on willingness to vaccinate dogs. Awareness campaigns in communities often target children, but do not consider other key individuals in the prevention chain. Understanding factors related to dog ownership and household-level responsibility for dog vaccination and child health is critical to the design of vaccination strategies. We investigated who makes household decisions about dogs and on health care for children in rural Tanzania. In the Kilosa district, in-depth interviews with 10 key informants were conducted to inform analysis of data from a household survey of 799 households and a survey on Knowledge Attitudes and Practices of 417 households. The in-depth interviews were analysed using framework analysis. Descriptive analysis showed responsibilities for household decisions on dogs’ and children’s health. Multivariate analysis determined factors associated with the probability of dogs being owned and the number of dogs owned, as well as factors associated with the responsibility for child health. Dog ownership varied considerably between villages and even households. The number of dogs per household was associated with the size of a household and the presence of livestock. Children are not directly involved in the decision to vaccinate a dog, which is largely made by the father, while responsibility for seeking health care if a child is bitten lies with the mother. These novel results are relevant for the design and implementation of rabies interventions. Specifically, awareness campaigns should focus on decision-makers in households to improve rabies prevention practices and on the understanding of processes critical to the control of zoonoses more broadly., Author summary The design of interventions tackling diseases transmitted between animals and humans requires an understanding of healthcare patterns related to both human and animal hosts. The control of dog-mediated rabies is a good example of this need. Rabies is still a major problem in Tanzania, where children are most at risk, and more than 40% of deaths are in children under 15 years old. While the vaccination of dogs against rabies is an effective method for controlling the disease, dog vaccination coverage is too low and depends on the willingness of dog owners to vaccinate. If a person is bitten by a rabid dog, the only way to prevent death is to receive post-exposure prophylaxis (PEP) in time. Hence, understanding factors related to dog ownership and responsibility for dog vaccination and child health is critical to the design of vaccination strategies. This study found that it is important to understand the role of these processes critical to the control of zoonoses, so that disease prevention campaigns can focus on a range of decision-makers, particularly those in households.

Estimates of dog population sizes are a prerequisite for delivering effective canine rabies control. However, dog population sizes are generally unknown in most rabies-endemic areas. Several approaches have been used to estimate dog populations but without rigorous evaluation. We compare post-vaccination transects, household surveys, and school-based surveys to determine which most precisely estimates dog population sizes. These methods were implemented across 28 districts in southeast Tanzania, in conjunction with mass dog vaccinations, covering a range of settings, livelihoods, and religious backgrounds. Transects were the most precise method, revealing highly variable patterns of dog ownership, with human/dog ratios ranging from 12.4:1 to 181.3:1 across districts. Both household and school-based surveys generated imprecise and, sometimes, inaccurate estimates, due to small sample sizes in relation to the heterogeneity in patterns of dog ownership. Transect data were subsequently used to develop a predictive model for estimating dog populations in districts lacking transect data. We predicted a dog population of 2,316,000 (95% CI 1,573,000–3,122,000) in Tanzania and an average human/dog ratio of 20.7:1. Our modelling approach has the potential to be applied to predicting dog population sizes in other areas where mass dog vaccinations are planned, given census and livelihood data. Furthermore, we recommend post-vaccination transects as a rapid and effective method to refine dog population estimates across large geographic areas and to guide dog vaccination programmes in settings with mostly free roaming dog populations.

A Rabies Elimination Demonstration Project was implemented in Tanzania from 2010 through to 2015, bringing together government ministries from the health and veterinary sectors, the World Health Organization, and national and international research institutions. Detailed data on mass dog vaccination campaigns, bite exposures, use of post-exposure prophylaxis (PEP), and human rabies deaths were collected throughout the project duration and project areas. Despite no previous experience in dog vaccination within the project areas, district veterinary officers were able to implement district-wide vaccination campaigns that, for most part, progressively increased the numbers of dogs vaccinated with each phase of the project. Bite exposures declined, particularly in the southernmost districts with the smallest dog populations, and health workers successfully transitioned from primarily intramuscular administration of PEP to intradermal administration, resulting in major cost savings. However, even with improved PEP provision, vaccine shortages still occurred in some districts. In laboratory diagnosis, there were several logistical challenges in sample handling and submission but compared to the situation before the project started, there was a moderate increase in the number of laboratory samples submitted and tested for rabies in the project areas with a decrease in the proportion of rabies-positive samples over time. The project had a major impact on public health policy and practice with the formation of a One Health Coordination Unit at the Prime Minister’s Office and development of the Tanzania National Rabies Control Strategy, which lays a roadmap for elimination of rabies in Tanzania by 2030 by following the Stepwise Approach towards Rabies Elimination (SARE). Overall, the project generated many important lessons relevant to rabies prevention and control in particular and disease surveillance in general. Lessons include the need for (1) a specific unit in the government for managing disease surveillance; (2) application of innovative data collection and management approaches such as the use of mobile phones; (3) close cooperation and effective communication among all key sectors and stakeholders; and (4) flexible and adaptive programs that can incorporate new information to improve their delivery, and overcome challenges of logistics and procurement.

BackgroundWith a global target set for zero human deaths from dog-mediated rabies by 2030 and some regional programmes close to eliminating canine rabies, there is an urgent need for enhanced surveillance strategies suitable for declaring freedom from disease and elimination of transmission with known confidence.MethodsUsing exhaustive contact tracing across settings in Tanzania we generated detailed data on rabies incidence, rabid dog biting behaviour and health-seeking behaviour of bite victims. Using these data we compared case detection of sampling-based and enhanced surveillance methodologies and investigated elimination verification procedures.FindingsWe demonstrate that patients presenting to clinics with bite injuries are sensitive sentinels for identifying dog rabies cases. Triage of patients based on bite history criteria and investigation of suspicious incidents can confirm >10% of dog rabies cases and is an affordable approach that will enable validation of disease freedom following two years without case detection. Approaches based on sampling the dog population without using bite-injury follow-up were found to be neither sensitive nor cost-effective.InterpretationThe low prevalence of rabies, and short window in which disease can be detected, preclude sampling-based surveillance. Instead, active case finding guided by bite-patient triage is needed as elimination is approached. Our proposed methodology is affordable, practical and supports the goal of eliminating human rabies deaths by improving administration of lifesaving post-exposure prophylaxis for genuinely exposed but untreated contacts. Moreover, joint investigations by public health and veterinary workers will strengthen intersectoral partnerships and capacity for control of emerging zoonoses.

Rabies can be eliminated by achieving comprehensive coverage of 70% of domestic dogs during annual mass vaccination campaigns. Estimates of vaccination coverage are, therefore, required to evaluate and manage mass dog vaccination programs; however, there is no specific guidance for the most accurate and efficient methods for estimating coverage in different settings. Here, we compare post-vaccination transects, school-based surveys, and household surveys across 28 districts in southeast Tanzania and Pemba island covering rural, urban, coastal and inland settings, and a range of different livelihoods and religious backgrounds. These approaches were explored in detail in a single district in northwest Tanzania (Serengeti), where their performance was compared with a complete dog population census that also recorded dog vaccination status. Post-vaccination transects involved counting marked (vaccinated) and unmarked (unvaccinated) dogs immediately after campaigns in 2,155 villages (24,721 dogs counted). School-based surveys were administered to 8,587 primary school pupils each representing a unique household, in 119 randomly selected schools approximately 2 months after campaigns. Household surveys were conducted in 160 randomly selected villages (4,488 households) in July/August 2011. Costs to implement these coverage assessments were $12.01, $66.12, and $155.70 per village for post-vaccination transects, school-based, and household surveys, respectively. Simulations were performed to assess the effect of sampling on the precision of coverage estimation. The sampling effort required to obtain reasonably precise estimates of coverage from household surveys is generally very high and probably prohibitively expensive for routine monitoring across large areas, particularly in communities with high human to dog ratios. School-based surveys partially overcame sampling constraints, however, were also costly to obtain reasonably precise estimates of coverage. Post-vaccination transects provided precise and timely estimates of community-level coverage that could be used to troubleshoot the performance of campaigns across large areas. However, transects typically overestimated coverage by around 10%, which therefore needs consideration when evaluating the impacts of campaigns. We discuss the advantages and disadvantages of these different methods and make recommendations for how vaccination campaigns can be better monitored and managed at different stages of rabies control and elimination programs.

Katie Hampson and colleagues describe their experience of developing and deploying a large-scale rabies surveillance system based on mobile phones in southern Tanzania.

There are a number of errors in Table 3. The table legend should read: Breakdown of economic costs of rabies by cluster in millions of USD. The headings for columns six, seven, and eight are incorrect. They should be in the following order: Dog vaccination, Dog population management, Livestock losses. Please see the correct Table 3 below. Table 3 Breakdown of economic costs of rabies by cluster in millions of USD.

An estimated 59 000 people die annually from rabies, keeping this zoonosis on the forefront of neglected diseases, especially in the developing world. Most deaths occur after being bitten by a rabid dog. Those exposed to a suspect rabid animal should receive appropriate post-exposure prophylaxis (PEP) or risk death. However, vaccination of dogs to control and eliminate canine rabies at the source has been implemented in many places around the world. Here, we analysed the vaccination and cost data for one such campaign in the area surrounding and including Dar es Salaam, Tanzania and estimated the cost per dog vaccinated. We also estimated the cost of human PEP. We found that the cost per dog vaccinated ranged from $2.50 to $22.49 across districts and phases, with the phase average ranging from $7.30 to $11.27. These figures were influenced by over purchase of vaccine in the early phases of the programme and the significant costs associated with purchasing equipment for a programme starting from scratch. The cost per human PEP course administered was approximately $24.41, with the average patient receiving 2.5 of the recommended four vaccine doses per suspect bite. This study provides valuable financial insights into programme managers and policymakers working towards rabies elimination.

Many of the pathogens perceived to pose the greatest risk to humans are viral zoonoses, responsible for a range of emerging and endemic infectious diseases. Phylogeography is a useful tool to understand the processes that give rise to spatial patterns and drive dynamics in virus populations. Increasingly, whole-genome information is being used to uncover these patterns, but the limits of phylogenetic resolution that can be achieved with this are unclear. Here, whole-genome variation was used to uncover fine-scale population structure in endemic canine rabies virus circulating in Tanzania. This is the first whole-genome population study of rabies virus and the first comprehensive phylogenetic analysis of rabies virus in East Africa, providing important insights into rabies transmission in an endemic system. In addition, sub-continental scale patterns of population structure were identified using partial gene data and used to determine population structure at larger spatial scales in Africa. While rabies virus has a defined spatial structure at large scales, increasingly frequent levels of admixture were observed at regional and local levels. Discrete phylogeographic analysis revealed long-distance dispersal within Tanzania, which could be attributed to human-mediated movement, and we found evidence of multiple persistent, co-circulating lineages at a very local scale in a single district, despite on-going mass dog vaccination campaigns. This may reflect the wider endemic circulation of these lineages over several decades alongside increased admixture due to human-mediated introductions. These data indicate that successful rabies control in Tanzania could be established at a national level, since most dispersal appears to be restricted within the confines of country borders but some coordination with neighbouring countries may be required to limit transboundary movements. Evidence of complex patterns of rabies circulation within Tanzania necessitates the use of whole-genome sequencing to delineate finer scale population structure that can that can guide interventions, such as the spatial scale and design of dog vaccination campaigns and dog movement controls to achieve and maintain freedom from disease.

Over the past 20 years, major progress has been made in our understanding of critical aspects of rabies epidemiology and control. This paper presents results of recent research, highlighting methodological advances that have been applied to burden of disease studies, rabies epidemiological modelling and rabies surveillance. These results contribute new insights and understanding with regard to the epidemiology of rabies and help to counteract misperceptions that currently hamper rabies control efforts in Africa. The conclusion of these analyses is that the elimination of canine rabies in Africa is feasible, even in wildlife-rich areas, through mass vaccination of domestic dogs and without the need for indiscriminate culling to reduce dog population density. Furthermore, the research provides valuable practical insights that support the operational planning and design of dog vaccination campaigns and rabies surveillance measures.