Rabies typically presents as an acute encephalomyelitis with an extremely high fatality rate. It is primarily a zoonotic infection in humans, and the disease is almost entirely preventable with timely postexposure prophylaxis.
EPIDEMIOLOGY AND PATHOGENESIS
Rabies is caused by highly neurotropic negative-stranded RNA lyssavirus variants in the family Rhabdoviridae. Infection spreads from terrestrial mammals to humans by introduction of infectious saliva by bites or scratches, through mucous membrane exposures, and rarely, by aerosol inhalations. It is not known to cross intact skin. Rare human-to-human transmissions are reported after organ transplantation.
Transmission by rabid dogs poses the greatest hazard worldwide. A 2015 study estimates that canine rabies causes approximately 59,000 human deaths annually worldwide. The majority of cases occur in Asia and Africa, with India accounting for over 35% of global rabies burden.
With mass vaccination of dogs, canine rabies has been eliminated in the United States. However, unvaccinated dogs and cats can become infected from rabid wildlife. Bats are the source of most human rabies in the United States. In many cases, bat-associated rabies occurs without a recognized bite. Rabies exposure can also occur through contact with skunks, raccoons, coyotes, foxes, and many other species. Rabies is not endemic in rodents or lagomorphs.
Rabies may occur in any climate or season, and susceptibility does not seem to vary with age, sex, or race. The incidence of rabies infection is highest in children, probably because they are more likely to be bitten by dogs and more likely to have multiple bites in high-risk sites. In the United States, an average of 3 human cases occur per year. Some of these cases are due to imported rabies in travelers to canine rabies–endemic areas. The attack rate in persons bitten by rabid animals is difficult to estimate, and it depends on the location of the wound, the depth of the bite, the presence of saliva infected with virus, and the protection afforded by clothing. Following inoculation, rabies virus enters the nerves either directly or after local replication. The nicotinic acetylcholine receptors are believed to be important for viral entry. In vitro studies have identified 2 more putative receptors—neural cell adhesion molecule and p75 neutrophin receptor—with probable role in infection and viral spread. Rabies virus reaches the central nervous system without a viremic phase via axonal transport in a retrograde fashion. Rabies virus localizes to areas of rich cholinergic innervation including amygdala, hippocampus, thalamus, hypothalamus, and basal ganglia. The pathologic changes are minimal, and the infected neurons do not show morphologic signs of degeneration. Perivascular infiltration with lymphocytes, polymorphonuclear leukocytes, and plasma cells is seen histologically. Rabies infection frequently causes cytoplasmic eosinophilic inclusion bodies (Negri bodies) found most commonly in the hippocampus and Purkinje cells of the cerebellum. After infection of the brain, the virus travels via the sensory and autonomic nervous system to the eyes, salivary glands, skin, and ...