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

Abstract

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.

Figure 1

Decision tree covering rabies exposure, health seeking, and health outcomes, including death due to rabies or prevention through PEP PEP provided to individuals bitten by healthy animals results in costs but does not avert deaths. For the full decision tree, see appendix. PEP=post-exposure prophylaxis.

Figure 2

DALYs (undiscounted; A), deaths (undiscounted; B), cost per DALYs averted (discounted; C), and cost per death averted (discounted; D) from 2020 to 2035 under the modelled scenarios Estimated outcomes presented with 95% PIs. Estimates do not include costs of dog vaccinations and only show the cost-effectiveness of PEP incremental to dog vaccination. Costs of IBCM are assumed to be covered by introductory grants (together with improved PEP access). Modelling assumptions are shown in panel and results in appendix. Only the base case is shown for scenario 2—ie, scenario 2a base case. DALYs=disability-adjusted life-years. IBCM=integrated bite case management. PEP=post-exposure prophylaxis. PI=prediction interval. RIG=rabies immunoglobulin. S=scenario. Vax=vaccination.

Figure 3

Projected outcomes under different scenarios over the 2020–35 time period Estimated outcomes per year presented with 95% PIs. (A) Human deaths from rabies (× 1000); (B) people initiating courses of PEP (× 1000); (C) vials of vaccine (× 1000) required for all 67 countries (top) and for selected countries (Bangladesh, Ethiopia, Kenya, and Myanmar) according to the status quo (scenario 1), under improved PEP access (scenario 2, base case), and with improved access to PEP vaccines concomitant with mass dog vaccination (scenario 4b). The step changes correspond to the timing of improvements in access to PEP and introduction of dog vaccination programmes. Bangladesh, Ethiopia, and Kenya are all phase 1 countries (implementation in 2020) in the Global Strategic Plan (appendix), whereas Myanmar is a phase 2 country (implementation in 2022). PEP=post-exposure prophylaxis. PI=prediction interval. S=scenario. Vax=vaccination.

Figure 4

The cost-effectiveness plane showing the ICERs for dog vaccination scenarios Under dog vaccination (scenarios 4a–c) improved PEP access (scenarios 4b and 4c) all have greater health benefits and similar or lower costs. The differences between clusters relate to the size of the populations at risk. ICER=incremental cost-effectiveness ratio. IBCM=integrated bite case management. PEP=post-exposure prophylaxis. Vax=vaccination.