Rabies: Virus and Disease

Abstract This article summarises the current literature on rabies and the aetiological agents responsible for this disease, which includes all members of the Lyssavirus genus, of which rabies virus ( RABV ) is the prototype species. Members of the orders Chiroptera and Carnivora serve as maintenance reservoirs for all recognised lyssavirus species and knowledge of the diversity, evolution and geographical range of these viruses is continually improving. Many mammalian species, including humans, are susceptible to spill‐over infections from the maintenance hosts. Despite the availability of efficacious prophylactics, once clinical signs develop, the disease is almost invariably fatal. Effective rabies control requires elimination of the disease from animal reservoirs. In developed countries, parenteral dog vaccination and oral vaccination of wildlife have effectively controlled rabies in many regions but socioeconomic factors limit the application of similar measures in many developing countries where the vast majority of human cases are reported. Better understanding of disease pathogenesis and host immune responses is sought in efforts to develop effective therapeutic interventions. Key Concepts Rabies is a neurological disease that can affect almost all mammals and is almost invariably fatal once clinical signs develop. Rabies is caused by all members of the Lyssavirus genus, bullet‐shaped neurotropic viruses with small RNA genomes, which are normally transmitted in virus‐laden saliva through bites. The vast majority of human rabies cases are the result of exposure to rabid animals. Prevention of human disease is undertaken by a regimen of timely post‐exposure prophylaxis. Distinct Lyssavirus species and variants thereof are maintained in dogs in many developing countries and by several wildlife species including foxes, skunks, raccoons, raccoon dogs, mongooses, jackals and many species of bats throughout much of the world. Through a series of viral–host interactions, rabies virus (RABV) has evolved mechanisms that maintain the neural network required for its propagation and spread within the infected host while avoiding clearance by the host's immune system. Knowledge of the diversity of the Lyssavirus genus is steadily expanding with increased surveillance and development of molecular tools to enable rapid characterisation of new isolates. Current vaccines and biologicals are ineffective against the more diverse members of the genus, thereby indicating that novel reagents with broader efficacy may be required for future disease control. Ultimately, control and eradication of rabies will require elimination of the disease from animal reservoirs through the application of efficacious and cost‐effective methods of animal vaccination.