Jane E. Sykes and Bruno B. Chomel

Etiologic Agent and Epidemiology

Rabies is a deadly, zoonotic, neurologic disease caused by a bullet-shaped, enveloped RNA virus that belongs to the genus Lyssavirus (from Lyssa, the Greek goddess of madness, rage, and frenzy) (Figure 13-1). The virus is fragile in the environment, and readily inactivated by a variety of disinfectants, soaps, ultraviolet light, and heat. It can survive up to 3 to 4 days in carcasses at 20°C, and longer with refrigeration.^2,3 Freezing tissues at temperatures less than −20°C may prolong survival of the virus for years.

There are seven lyssavirus genotypes (Table 13-1). Classical rabies virus belongs to genotype 1. The remaining six lyssavirus genotypes primarily infect bats and less frequently cause fatal human encephalitis, which is clinically indistinguishable from classical rabies.⁴ Thus, although Taiwan, Australia, New Zealand, Iceland, the United Kingdom, Japan, most of western Europe, Fiji, Hawaii, and Guam are designated terrestrial rabies-free, lyssaviruses capable of causing fatal encephalitis in humans exist in some of these regions, including Australia, Western Europe, and the United Kingdom (Figure 13-2). The remaining information in this chapter pertains only to genotype 1 rabies virus infections.

Infection with rabies virus most commonly occurs as a result of inoculation of virus-containing saliva into a bite wound, in the large majority of the cases after a dog bite. Other routes of transmission reported in species other than dogs and cats are rare and include corneal or solid-organ transplantation in human patients⁵; aerosol transmission, such as that occurring within caves containing large numbers of bats^6,7; and transmission after ingestion of infected tissues or milk.^6,8

All warm-blooded animals are susceptible to rabies, although dogs, wild carnivores, and bats are considered the main natural reservoirs of rabies virus. In general, wolves, foxes, coyotes, jackals, dogs, cattle, raccoons, skunks, bats, and mongooses are highly susceptible to infection. Moderately susceptible hosts include cats, ferrets, primates, sheep, goats, and horses. Marsupials, including opossums, have a low degree of susceptibility. Some bird species can be experimentally infected but do not develop clinical signs and are unlikely hosts.⁹

Not every bite from a rabid animal leads to rabies virus infection, and infection may not always culminate in death, unless clinical signs develop. Factors influencing the outcome after a bite from a rabid animal include the proximity of the bite site to the central nervous system (CNS), the degree of innervation of the bite site, the age of the host (young animals are more susceptible), the amount of virus inoculated, and the neuroinvasiveness of the rabies virus variant involved. If left untreated, up to 60% of humans bitten by a rabid dog on the head or neck develop rabies, compared with up to 40% of those bitten on the hand, and 10% of those bitten on the trunk or leg.¹⁰

Rabies viruses that circulate within a certain geographic region are adapted to specific dominant reservoir hosts (e.g., bat rabies virus variants or raccoon rabies virus variants). All rabies virus variants can infect and cause disease in animals other than their reservoir hosts (spillover hosts). In all host species, rabies is usually an acute fatal illness, although some animals, such as bats and skunks, have a more prolonged course of illness than others, such as foxes, coyotes, or raccoons. The possibility of a subclinical carrier state, especially in bats, has been suggested based on the detection of rabies virus antibody and, rarely, the virus itself in some reservoir host species that are not showing signs of illness.⁴

Over the past 50 years, owing to mandatory vaccination and control programs, domestic animal rabies in the United States has decreased in prevalence, whereas wildlife rabies has increased. The dog rabies virus variant was considered eradicated from the United States at the beginning of the 21st century. Currently, cats are more commonly reported with rabies in the United States (about 300 cases/year) than dogs (fewer than 100 cases/year), most likely reflecting rabies vaccination practices (Figure 13-3, A). No feline rabies virus variant has been described. The geographic distribution of feline and canine rabies follows that of regions where wildlife rabies is endemic. Most cats and dogs are infected with the rabies virus variant that is associated with the major wildlife reservoir host in their respective geographic location (see Figure 13-3, B). Rabid cats are most often reported from the northeastern United States, mid-Atlantic, and south-Atlantic states, with lesser numbers from the north and south central states. The eastern distribution of feline rabies follows the distribution of raccoon rabies.^11,12 Rarely, cats are infected from bats. Rabies in dogs and cats is most commonly reported from the north central, south central, and Atlantic states (see Figure 13-3, A). Dogs may be infected with rabies virus variants from skunks or raccoons. Infected dogs have also been imported into the United States from other countries where canine rabies variants are endemic.^13,14 In Europe, the major wildlife reservoir species have been foxes and raccoon dogs, and in South Africa, jackals and mongooses predominate. In western Europe, fox rabies has largely been eliminated as a result of mass vaccination campaigns. Spillover occurs from wildlife reservoir hosts to domestic animal species, which subsequently contact humans. Nevertheless, the vast majority of human cases in North America result from contact with infected bats, which are present in all states except Hawaii (see Public Health Aspects). Rabies in rodents and lagomorphs is rare, possibly because they are always killed by the bite of a rabid animal. In the United States, most reports have been from woodchucks in raccoon endemic areas.¹⁵ A few cases of rabies in pet ferrets, rabbits, and a pet guinea pig have been described.¹⁶

Although rabies occurs in cats and dogs of any age, it is most frequently reported in young dogs and cats, with a median age of 1 year for both cats and dogs in one study; 75% of animals were 3 years of age or younger.¹⁷ Rabies can occur in puppies and kittens that have not yet reached the age at which routine rabies vaccination is approved, which is an emerging issue as a result of illegal importation of pet dogs from Mexico through California and Texas. Male dogs may be slightly more predisposed, and most dogs and cats with rabies have not been neutered and live in rural environments, frequently being unrestrained at night.^11,17 In the United States, some degree of seasonality occurs for rabies in dogs and cats, which correlates with seasonal increases in rabid raccoons and skunks.^11,17 For the majority of cats and dogs with rabies, a history of known contact with wild animals or a wound is lacking.

Clinical Features

Diagnosis

Rabies should be suspected in dogs and cats evaluated for sudden onset of behavioral changes and flaccid paralysis, especially in rabies-endemic regions, or in animals imported from rabies-endemic countries. Although a particularly high degree of suspicion is warranted for animals that lack a vaccination history for rabies, the disease has been reported in partially and completely vaccinated dogs and cats,11,17,23 so a history of rabies vaccination should not be used to dismiss suspicion for rabies.