How geographic access to care shapes disease burden: the current impact of post-exposure prophylaxis and potential for expanded access to prevent human rabies deaths in Madagascar

BackgroundPost-exposure prophylaxis (PEP) is highly effective at preventing human rabies deaths, however access to PEP is limited in many rabies endemic countries. The 2018 decision by Gavi to add human rabies vaccine to its investment portfolio should expand PEP availability and reduce rabies deaths. We explore how geographic access to PEP impacts the rabies burden in Madagascar and the potential benefits of improved provisioning.Methodology & Principal FindingsWe use travel times to the closest clinic providing PEP (N=31) as a proxy for access. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree framework we extrapolate rabies deaths and reporting and find that geographic access to PEP shapes burden sub-nationally. We estimate 960 human rabies deaths annually (95% Prediction Intervals (PI):790 - 1120), with PEP averting an additional 800 deaths (95% PI: 800 (95% PI: 640 - 970) each year. Under these assumptions, we find that expanding PEP to one clinic per district could reduce deaths by 19%, but even with all major health centers provisioning PEP (1733 additional clinics), we still expect substantial rabies mortality. Our quantitative estimates are most sensitive to assumptions of underlying rabies exposure incidence, but qualitative patterns of the impacts of travel times and expanded PEP access are robust.Conclusions & SignificancePEP is effective at preventing rabies deaths, and in the absence of strong surveillance, targeting underserved populations may be the most equitable way to provision PEP. Our framework could be used to guide PEP expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted. While better PEP access should save many lives, improved outreach and surveillance is needed and if rolled out with Gavi investment could catalyze progress towards achieving zero rabies deaths.Author SummaryCanine rabies causes an estimated 60,000 deaths each year across the world, primarily in low- and middle-income countries where people have limited access to both human vaccines (post-exposure prophylaxis or PEP) and dog rabies vaccines. Given that we have the tools to prevent rabies deaths, a global target has been set to eliminate deaths due to canine rabies by 2030, and recently, Gavi, a multilateral organization that aims to improve access to vaccines in the poorest countries, added human rabies vaccine to it’s portfolio. In this study, we estimated reported bite incidence in relation to travel times to clinics provisioning PEP, and extrapolate human rabies deaths in Madagascar. We find that PEP currently averts around 800 deaths each year, but that the burden remains high (1000 deaths/ year), particularly in remote, hard-to-reach areas. We show that expanding PEP availability to more clinics could significantly reduce rabies deaths in Madagascar, but our results suggest that expansion alone will not eliminate deaths. Combining PEP expansion with outreach, surveillance, and mass dog vaccination programs will be necessary to move Madagascar, and other Low- and Middle-Income countries, forward on the path to rabies elimination.