The potential effect of improved provision of rabies post-exposure prophylaxis in Gavi-eligible countries: a modelling study

Background: 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. Methods: 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. Findings: 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. Interpretation: 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. Funding: World Health Organization

Modelling the factors affecting the probability for local rabies elimination by strategic control

Dog rabies has been recognized from ancient times and remains widespread across the developing world with an estimated 59,000 people dying annually from the disease. In 2011 a tri-partite alliance consisting of the OIE, the WHO and the FAO committed to globally eliminating dog-mediated human rabies by 2030. Regardless of global support, the responsibility remains with local program managers to implement successful elimination programs. It is well known that vaccination programs have a high probability of successful elimination if they achieve a population-coverage of 70%. It is often quoted that reducing population turnover (typically through sterilizations) raises the probability for local elimination by maintaining herd immunity for longer. Besides this, other factors that affect rabies elimination are rarely mentioned. This paper investigates the probability for local elimination as it relates to immunity, fecundity, dog population size, infectivity (bite rates), in-migration of immunenaïve dogs, and the initial incidence. To achieve this, an individual-based, stochastic, transmission model was manipulated to create a dataset covering combinations of factors that may affect elimination. The results thereof were analysed using a logistic regression model with elimination as the dependent variable. Our results suggest that smaller dog populations, lower infectivity and lower incidence (such as when epidemics start with single introductions) strongly increased the probability for elimination at wide ranges of vaccination levels. Lower fecundity and lower in-migration had weak effects. We discuss the importance of these findings in terms of their impact and their practical application in the design of dogmediated rabies control programs

Modelling the factors affecting the probability for local rabies elimination by strategic control.

Dog rabies has been recognized from ancient times and remains widespread across the developing world with an estimated 59,000 people dying annually from the disease. In 2011 a tri-partite alliance consisting of the OIE, the WHO and the FAO committed to globally eliminating dog-mediated human rabies by 2030. Regardless of global support, the responsibility remains with local program managers to implement successful elimination programs. It is well known that vaccination programs have a high probability of successful elimination if they achieve a population-coverage of 70%. It is often quoted that reducing population turnover (typically through sterilizations) raises the probability for local elimination by maintaining herd immunity for longer. Besides this, other factors that affect rabies elimination are rarely mentioned. This paper investigates the probability for local elimination as it relates to immunity, fecundity, dog population size, infectivity (bite rates), in-migration of immune-naïve dogs, and the initial incidence. To achieve this, an individual-based, stochastic, transmission model was manipulated to create a dataset covering combinations of factors that may affect elimination. The results thereof were analysed using a logistic regression model with elimination as the dependent variable. Our results suggest that smaller dog populations, lower infectivity and lower incidence (such as when epidemics start with single introductions) strongly increased the probability for elimination at wide ranges of vaccination levels. Lower fecundity and lower in-migration had weak effects. We discuss the importance of these findings in terms of their impact and their practical application in the design of dog-mediated rabies control programs

A bioeconomic model for the optimization of local canine rabies control.

We present a new modeling tool that can be used to maximize the impact of canine rabies management resources that are available at the local level. The model is accessible through a web-based interface that allows for flexibility in the management strategies that can be investigated. Rabies vaccination, sterilization, chemo-contraception, and euthanasia can be specified and limited to specific demographic groups. Additionally, we allowed for considerable complexity in the specification of management costs. In many areas, the costs of contacting additional dogs increases as management effort increases, and this can have important strategic implications. We illustrated the application of the model by examining several alternative management strategies in an area of Mpumalanga Province, South Africa. Our results based on this dog population suggested that puppies should be vaccinated and sterilization would not be optimal if the spatial extent of management is not large (and perhaps not even then). Furthermore, given a sufficient budget, it was evident that vaccination campaigns should be repeated annually