Rabies, Still Neglected after 125 Years of Vaccination

Rabies is a viral zoonotic infection ofthe central nervous system caused by alyssavirus. The disease is fatal withoutproper post exposure prophylaxis (PEP).In July 1885, Louis Pasteur obtained hisfirst success against rabies by vaccinatingJoseph Meister, a 9-year-old boy present-ing with multiple deep bite wounds [1].After more than 700 successful inocula-tions, Pasteur launched an internationalsubscription and opened the world’s firstresearch institute dedicated to the preven-tion of rabies and other infectious diseases.The Institut Pasteur was born. Due tosubstantial advances during the 20thcentury, safe and effective human andanimal vaccines based on tissue culturemethodologies are available today. Today,125 years later, Institut Pasteur is at thecore of an international network of 30institutes. Through its numerous institu-tions established in enzootic areas, theworldwide contribution of the InstitutPasteur International Network to rabiessurveillance and control is still of para-mount importance. Each year, the Inter-national Network is responsible for PEPadministration to more than 180,000exposed patients, mainly in Southeast Asiaand Africa. Scientists and health staff arealso involved in various national commit-tees that work on the development andsuccessful implementation of rabies con-trol programs.Sadly, whereas extensive efforts indeveloped countries have largely con-trolled dog (the United States and Europe)and fox (western and central Europe)rabies [2,3], dog rabies remains enzooticin much of the world, and 15 millionpeople require PEP every year. Rabies isconsidered one of the most neglecteddiseases in the world’s developing coun-tries with the greatest burden in poor ruralcommunities, and disproportionately inchildren. According to the World HealthOrganization (WHO), 30% to 50% of the55,000 victims estimated each year areindividuals under 15 years of age [4]. Over95% of these human rabies cases areconcentrated in Asia (especially in India)and Africa, and 99% of them are trans-mitted by dogs. There are several reasonsfor the lack of accurate data, includingweak or non-existent rabies surveillancesystems; under-reporting of cases by localcommunities and central authorities; un-reliable diagnosis of cases, which isgenerally based on clinical criteria ratherthan laboratory confirmation; and inade-quate legislation for compulsory notifica-tion of cases. The absence of accurate dataon disease burden, upon which regionaland national priorities for research andcontrol are based, leads to a vicious cycleof indifference and neglect [5].The question now is why, despite theavailability of safe and effective humanvaccines, human rabies deaths continue toescalate in many parts of the world. Thereare several general and specific explana-tions for the continued burden of dograbies [6–8].In general, there is a lack of awarenessamongst policy-makers of the rabies bur-den and impacts and the need forprioritizing resources towards its control.Further, despite the widely advocatedneed for intersectoral collaboration be-tween government ministries, the recogni-tion of roles and responsibilities amongstagencies as well as integration of budgetsacross ministries still poses considerablechallenges.Mass vaccination of dogs is the mostcost-effective way to achieve a significantand lasting reduction in the number ofhuman deaths from rabies [9]. However,such prevention efforts are often notprioritized by national governments ineven the most endemic countries. Amongthe reasons for the low priority affordedrabies are, as for many neglected tropicaldiseases, its predominance in remote ruralareas and its disproportionate impact onpeople living in extreme poverty. There-fore, lack of resources, gaps in epidemio-logical knowledge (e.g., level of vaccina-tion coverage needed in any given setting),lack of in-country expertise on implemen-tation of canine rabies control strategies,and sustainability issues impair the successof such programs.Additionally, in most developing coun-tries (with some notable exceptions), thereis a lack of awareness among the popula-tion, including medical practitioners andhealth authorities, about the widespreadextent of the disease and the risk oftransmission from dogs to human popula-tions [6–8]. Additionally, the infrastruc-ture for the management of rabies expo-sure is scarce. Many people who areexposed to rabies do not seek PEP,because they are not aware of the risk ofcontracting this disease or because theylive in rural areas too far away from rabiesprevention centers, which are generallylocated in big cities. In some cases, theworld’s poorest people simply cannotafford the cost of PEP.A range of key scientific questions alsoremains unsolved, and there is an urgencyto promote research and development onthe fundamental aspects of rabies molec-ular pathobiology, improved control tools,and operational research. There is also aneed for multidisciplinary integrative ap-proaches that rely on the followingelements.1. It is essential to find ways to improveepidemiological surveillance using di-agnostic approaches to rabies based onvalidated protocols and specimens andevaluated under field conditions [10–12]. Epidemiological models are alsoneeded to better estimate the inci-dence of rabies [4,13,14]. Recentresearch on this topic published in thisjournal yielded rabies incidence for