Rajeev, Malavika, Guis, Hélène, Edosoa, Glenn, Mangahasimbola, Reziky, Hanitriniaina, Chantal, Randrianarijaona, Anjasoa, Mangahasimbola, Reziky Tiandraza, Hierink, Fleur, Ramiandrasoa, Ravo, Nely, José, Heraud, Jean-Michel, Andriamandimby, Soa Fy, Baril, Laurence, Metcalf, C. Jessica E., Hampson, Katie, Princeton University, Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité d’Épidémiologie et de Recherche clinique [Antananarivo, Madagascar], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Organisation Mondiale de la Santé - World Health Organization [Madagascar] (OMS/WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Réseau International des Instituts Pasteur (RIIP), Université d'Antananarivo, University of Geneva [Switzerland], Ministère de la Santé Publique [Antananarivo, Madagascar], Unité de Virologie [Antananarivo, Madagascar] (IPM), University of Glasgow, and This work was funded by grants from the Center for Health and Wellbeing and the Department of Ecology and Evolutionary Biology at Princeton University to CJEM and MR. MR is supported by an NSF Graduate Research Fellowship. KH is supported by the Wellcome Trust (207569/Z/17/Z). Funding for open access publication was made possible by support from the Princeton University Library Open Access Fund.
Background Post-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 findings We use spatially resolved data on numbers of bite patients seeking PEP across Madagascar and estimates of travel times to the closest clinic providing PEP (N = 31) in a Bayesian regression framework to estimate how geographic access predicts reported bite incidence. We find that travel times strongly predict reported bite incidence across the country. Using resulting estimates in an adapted decision tree, 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: 640–970) each year. Under these assumptions, we find that expanding PEP to one clinic per district (83 additional clinics) could reduce deaths by 19%, but even with all major primary clinics 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 & significance PEP 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. Given the potential for countries to use Gavi funding to expand access to PEP in the coming years, this framework could be used as a first step to guide expansion and improve targeting of interventions in similar endemic settings where PEP access is geographically restricted and baseline data on rabies risk is lacking. While better PEP access should save many lives, improved outreach, surveillance, and dog vaccination will be necessary, and if rolled out with Gavi investment, could catalyze progress towards achieving zero rabies deaths., Author summary Canine 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 incidence of patients seeking PEP 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 reaffirm that expansion alone is will not achieve the global goal of zero human deaths from dog-mediated rabies by 2030. 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.