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Rabies is one of the oldest known zoonoses. Recognized etiological agents consist of at least 15 proposed species of lyssaviruses with primary reservoirs residing in the Orders Carnivora and Chiroptera. A plethora of viral variants, maintained by a diverse set of abundant hosts, presents a formidable challenge to a strict concept of true disease eradication. Despite the availability of affordable and efficacious animal and human vaccines, today however dog rabies continues to escalate unabated across much of Asia and Africa, causing millions of suspect human exposures and tens of thousands of human rabies deaths annually. By identifying what hampers global human rabies elimination this chapter emphasizes that, given the global epidemiology of rabies, the "One Health" concept is key to solving the problem. Next to state of the art human rabies prevention, immunization and experimental therapy, it is obvious that human rabies can only be eliminated through rabies control at the animal source. This 'paradigm shift', however, needs new grassroot initiatives as well as political will and the closing of ranks of all stakeholders in the near future.

Rabies, an acute progressive encephalitis, is an ancient zoonosis. Its distribution encompasses all continents, except Antarctica. Agents consist of at least 11 species orgenotypes of rhabdoviruses, in the Genus Lyssavirus. Susceptible natural hosts include all mammals. Primary reservoirs reside in the Orders Carnivora and Chiroptera. A plethora of variants, maintained by a diversity of abundant hosts, presents a challenge to a strict concept of true eradication. Globally, the domestic dog remains the most significant species for viral transmission, responsible for millions of suspect human exposures and tens of thousands of fatalities. As such, this single major target provides an ideal opportunity for focused intervention programmes in humane disease prevention and control, driven by laboratory-based surveillance and guided via modern epidemiological insights. Historically, substantial technical progress throughout the 20th century led to the development of safe, affordable and efficacious animal and human vaccines, resulting in declining disease burdens in selected developed and developing countries. Regional and local disease resurgence occurs, due in part to a combination of political and economic instability, environmental perturbations, and shifting government priorities. Society must recall that despite the recent recognition of other important emerging infectious diseases, none exceed the case fatality rate of rabies. Given the clear relevance of rabies in public health, agriculture, and conservation biology, substantive international progress must continue towards enhanced public awareness, human rabies prevention, wildlife rabies control, and canine rabies elimination, with renewed collaborative vigour.