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Additional file 2. Vaccination coverage estimates. Estimates for each district for each year during which vaccination campaigns were undertaken. Details of the timings of the vaccination campaign are given for each year.

Additional file 3. Results of generalized linear models for the incidence of probable domestic dog rabies cases from models containing the mean domestic dog vaccination coverage from two years before cases occurred. The 95% confidence intervals for the estimates are shown in square brackets [].

Additional file 5. Results of generalized linear models for the incidence of probable jackal rabies cases from models containing the mean domestic dog vaccination coverage from two years before cases occurred. The 95% confidence intervals for the estimates are shown in square brackets [].

Additional file 1. Location of the probable animal rabies cases used within the subset analysis. Probable animal rabies cases are shown as black diamonds and include all species. The cases considered within the subset analysis are those located in the region outlined in blue. All cases included within the subset are within 10 km of another case.

Additional file 4. Results of generalized linear models for the incidence of probable domestic dog rabies cases from models containing the mean domestic dog vaccination coverage from three years before cases occurred. The 95% confidence intervals for the estimates are shown in square brackets [].

Additional file 6. Results of generalized linear models for the incidence of probable jackal rabies cases from models containing the mean domestic dog vaccination coverage from three years before cases occurred. The 95% confidence intervals for the estimates are shown in square brackets [].

Almost half of all countries in the world are effectively free of human deaths from dog-mediated rabies. But the disease still affects people in low- and middle-income countries, especially the rural poor, and children. Successful regional elimination of human rabies is attributable to advances in significant and sustained investment in dog vaccination, post-exposure vaccination and surveillance, illustrated by productive efforts to reduce human rabies in Latin America over the last 35 years. Nonetheless, countries still facing endemic rabies face significant barriers to elimination. Using the 2017 Global Strategic Plan to end human rabies deaths from dog-mediated rabies by 2030 as a reference point and an organizing framework, we assess progress toward global rabies elimination by examining the characteristics of successful regional control efforts and barriers to elimination. Although substantive barriers exist for countries where rabies remains endemic, advances in knowledge, technology, institutions, and economics provide a basis for optimism.

Dog-mediated rabies continues to kill tens of thousands of people every year in low- and middle-income countries despite being an entirely vaccine-preventable disease. WHO and partners have launched a global campaign to reach zero human deaths from dog-mediated rabies by 2030. The primary tools for reaching this target are mass dog vaccination to interrupt transmission in domestic dog populations that maintain infection, appropriate post-exposure prophylaxis (PEP) for rabies-exposed persons to prevent the fatal onset of disease, together with education to support their effective uptake. Models have been developed to assess the feasibility, impact and cost-effectiveness of these measures. From these models, we argue that the 2030 target of zero human rabies deaths is achievable, but will require concerted effort, engagement and investment. A proposed Gavi investment in human rabies vaccines has potential to drive progress towards the 2030 target; however, concomitant investment is needed to scale up mass dog vaccination or this target will be missed. Predicted economic benefits of mass dog vaccination vary according to national PEP provisioning and healthcare access. Integrated Bite Case Management can enhance surveillance and rationalize PEP use, but needs adapting to and integrating within local health systems and international reporting systems to improve PEP accountability, monitor impacts and support verification of disease freedom. Modelling approaches need refining to project realistic and geographically specific timelines for achieving targets. Model iterations informed by data on the implementation of interventions can be used to evaluate progress and guide future strategies. Critically such models are needed to advocate for investment, since the greatest risk to the ‘Zero by 30’ strategy is the limited long-term cross-sectoral or targeted financing to support countries to deliver and sustain mass dog vaccination.

Background: \ud Tens of thousands of people die from dog-mediated rabies annually. Deaths can be prevented through post-exposure prophylaxis for people who have been bitten, and the disease eliminated through dog vaccination. Current post-exposure prophylaxis use saves many lives, but availability remains poor in many rabies-endemic countries due to high costs, poor access, and supply.\ud \ud Methods: \ud We developed epidemiological and economic models to investigate the effect of an investment in post-exposure prophylaxis by Gavi, the Vaccine Alliance. We modelled post-exposure prophylaxis use according to the status quo, with improved access using WHO-recommended intradermal vaccination, with and without rabies immunoglobulin, and with and without dog vaccination. We took the health provider perspective, including only direct costs.\ud \ud Findings: \ud We predict more than 1 million deaths will occur in the 67 rabies-endemic countries considered from 2020 to 2035, under the status quo. Current post-exposure prophylaxis use prevents approximately 56 000 deaths annually. Expanded access to, and free provision of, post-exposure prophylaxis would prevent an additional 489 000 deaths between 2020 and 2035. Under this switch to efficient intradermal post-exposure prophylaxis regimens, total projected vaccine needs remain similar (about 73 million vials) yet 17·4 million more people are vaccinated, making this an extremely cost-effective method, with costs of US$635 per death averted and $33 per disability-adjusted life-years averted. Scaling up dog vaccination programmes could eliminate dog-mediated rabies over this time period; improved post-exposure prophylaxis access remains cost-effective under this scenario, especially in combination with patient risk assessments to reduce unnecessary post-exposure prophylaxis use.\ud \ud Interpretation: \ud Investing in post-exposure vaccines would be an extremely cost-effective intervention that could substantially reduce disease burden and catalyse dog vaccination efforts to eliminate dog-mediated rabies.\ud \ud Funding: \ud World Health Organization.

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.