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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.

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.

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.

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.

Background With increased global attention to neglected diseases, there has been a resurgence of interest in eliminating rabies from developing countries through mass dog vaccination. Tanzania recently embarked on an ambitious programme to repeatedly vaccinate dogs in 28 districts. To understand community perceptions and responses to this programme, we conducted an anthropological study exploring the relationships between dogs, society, geography and project implementation in the districts of Kilombero and Ulanga, Southern Tanzania. Methodology/Principal Findings Over three months in 2012, we combined the use of focus groups, semi-structured interviews, a household questionnaire and a population-based survey. Willingness to participate in vaccination was mediated by fear of rabies, high medical treatment costs and the threat of dog culling, as well as broader notions of social responsibility. However, differences between town, rural and (agro-) pastoralist populations in livelihood patterns and dog ownership impacted coverage in ways that were not well incorporated into project planning. Coverage in six selected villages was estimated at 25%, well below official estimates. A variety of problems with campaign mobilisation, timing, the location of central points, equipment and staff, and project organisation created barriers to community compliance. Resource-limitations and institutional norms limited the ability for district staff to adapt implementation strategies. Conclusions and Significance In the shadows of resource and institutional limitations in the veterinary sector in Africa, top-down interventions for neglected zoonotic diseases likes rabies need to more explicitly engage with project organisation, capacity and community participation. Greater attention to navigating local realities in planning and implementation is essential to ensuring that rabies, and other neglected diseases, are controlled sustainably., Author Summary Mass vaccination of dogs is the most effective strategy to eliminate dog-mediated human rabies from developing countries. In 2009, a large-scale elimination demonstration project was funded and coordinated by the Bill and Melinda Gates Foundation (BMGF) and the World Health Organisation (WHO) in three southern countries, including the United Republic of Tanzania. This paper explores community perceptions and responses to this programme in the districts of Kilombero and Ulanga, Southern Tanzania. The study was based on focus groups and interviews in 16 villages as well as a household questionnaire (n = 113), a population-based survey (n = 6,157 households) and key informant interviews (n = 24). The study showed that fear of rabies, the threat of dog culling and broader ideas of community responsibility drove compliance. However differences in local livelihoods shaped dog ownership patterns and the distribution of dogs in ways that were not explicitly addressed by project strategies. A survey in six villages found that only 25% of dogs had been vaccinated in 2011. We discuss the operational constraints and problems that lowered coverage as viewed by different actors at the district and village-level. A more explicit engagement with project organisation, capacity and community involvement are needed to address this low coverage.

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.