Rabies is an acute progressive viral infection of the central nervous system.1,2 The disease has affected humans and other animals for millennia. Although warm-blooded vertebrates are susceptible to experimental infection, only mammals are important hosts in nature. Rabies persists among the Carnivora and Chiroptera. The domestic dog is a primary reservoir on a global basis. Regionally, many wildlife species may serve as maintenance hosts. Transmission occurs by animal bite. Humans are affected by incidental infection from animals. The etiological agents are rod-shaped RNA viruses that belong to the genus Lyssavirus, in the Rhabdoviridae, a diverse family that includes a number of other agents affecting vertebrates, invertebrates, and plants.
Rabies exists on every continent, except Antarctica. Many island locations, such as in the Caribbean or Pacific Oceania, are fortunate and either never experienced rabies, or eliminated the disease by the application of control and quarantine measures. Other locations, such as parts of western Europe or the Americas, have controlled the disease in carnivores, but may experience enzootic disease among bats.
The occurrence of human rabies in Europe, Canada, and the United States has been reduced historically from scores of deaths annually to only a few cases per year. Human fatalities are much higher in the developing world.1,3,4 Typically, more than 50,000 persons, and millions of animals, die of rabies worldwide each year, and several million people receive rabies prophylaxis after exposure.1,3,4 Compared to developed countries, the diagnosis and reporting of human and animal rabies in many under developed areas of Asia, Africa, and Latin America is less than ideal. Data on the prevalence of the disease in many of these areas are often unreliable. The burden of rabies remains significant in many localities, where it causes otherwise preventable deaths, substantial anxiety, serious adverse effects from outdated vaccines, and incalculable costs to many individuals and their families.4 For example, the number of persons vaccinated for potential rabies exposure each year in the United States is estimated between 20,000 and 40,000 cases per year, whereas prophylaxis approaches a figure of a million exposures in India alone.3
The distribution of animal rabies is global in nature. Several different lyssaviruses serve as major etiological agents throughout the world. Each of these viral species is irregular in distribution and presumed reservoir attributes (Table 16-1). Owing to this diversity, with basic similarity to other RNA viruses, lyssaviruses lack proofreading enzymes. Consequently, during RNA replication, viral copy errors are made. Many of these replication errors are lethal, and do not result in competent progeny viruses. Molecular drift and eventual stability may occur when different variants arise and can overcome adaptive bottlenecks in certain animal populations. Such variants can be differentiated from each other by genetic, antigenic, ...