Rabies: Introduction - The Merck Veterinary Manual

Rabies: Introduction

Etiology and Epidemiology

Transmission and Pathogenesis

Management of Suspected Rabies Cases—Exposure of Pets

Zoonotic Risk

Rabies is an acute viral encephalomyelitis that principally affects carnivores and bats, although it can affect any mammal. It is invariably fatal once clinical signs appear. Rabies is found throughout the world, but a few countries claim to be free of the disease due either to successful elimination programs and/or to their island status and enforcement of rigorous quarantine regulations.

Etiology and Epidemiology:

Rabies is caused by lyssaviruses in the Rhabdovirus family. Lyssaviruses are usually confined to 1 major reservoir species in a given geographic area, although spillover to other species is common. Identification of different virus variants by laboratory procedures such as monoclonal antibody analysis or genetic sequencing has greatly enhanced understanding of rabies epidemiology. Generally, each virus variant is responsible for rabies transmission between members of the same species in a given geographic area. From an epidemiologic perspective, it is preferable to use the name of the species acting as the reservoir as an adjective: rabies maintained by dog-to-dog transmission is termed canine rabies, whereas rabies in a dog as a result of infection with a variant from a different reservoir, eg, skunk (or fox), should be referred to as skunk (or fox, etc) rabies in a dog.

In North America, distinct virus variants are responsible for rabies in dogs and coyotes in Mexico and south Texas, red and Arctic foxes in Canada and Alaska, raccoons along the eastern seaboard, gray foxes in Texas and a closely related variant in gray foxes in the southwestern USA. Two different variants are responsible for rabies in striped skunks, one in the south central states and the other in the north central states. Another skunk rabies virus variant is seen in California. The epidemiology of rabies in bats is complex, but in general, each variant found in bats may be assigned to a predominant bat species. Spillover from bats to terrestrial animals is seen infrequently. Most human cases of rabies in the USA in the past decade have been caused by bat rabies virus variants (especially the variant associated with Lasionycteris noctivagans , the silver-haired bat, and Pipistrellus subflavus , the Eastern Pipistrelle).

Rabies, raccoon

Reservoirs of rabies vary throughout the world. Canine rabies predominates in Africa, Asia, Latin America, and the Middle East. In North America and Europe, where canine rabies has been practically eliminated, rabies is maintained in wildlife. For many years, skunks were the most commonly reported rabid animal in the USA, but since 1990, rabid raccoons have been the most numerous. Canine rabies became established in coyotes ( Canis latrans ) in southern Texas and Mexico, with the potential to spread throughout much of the USA and Canada. Skunk, raccoon, and fox rabies are each found in fairly distinct geographic regions of North America, although some overlap occurs. Bat rabies is distributed throughout the USA and Central and South America. In Europe, red fox rabies predominates. In parts of northern and eastern Europe, rabies in raccoon dogs is of increasing concern. Rabies in insectivorous bats may be widely distributed in Europe. The vampire bat is an important reservoir in Mexico, Central and South America, and is the source of outbreaks in cattle. Other wild species play an important role in the transmission of rabies in certain areas, including mongooses in the Caribbean, southern Africa, and parts of Asia; jackals in certain parts of Africa; and wolves in parts of northern Europe.

No cat-to-cat transmission of rabies has been recorded, and no feline rabies virus variant is known. However, cats are the most commonly reported rabid domestic animal in the USA. Virus is present in the saliva of rabid cats, and people have developed rabies after being bitten by a rabid cat. Reported cases in domestic cats have outnumbered those in dogs in the USA every year since 1988.

Transmission and Pathogenesis:

Transmission is almost always by introduction of virus-laden saliva into the tissues, usually by the bite of a rabid animal. Although much less likely, it is possible for virus from saliva, salivary glands, or brain to cause infection by entering the body through other fresh wounds or through intact mucous membranes. Usually, saliva is infectious at the time that clinical signs occur, but it is possible for dogs and cats to shed virus for several days before onset of clinical signs. Viral shedding in skunks has been reported for up to 8 days prior to onset of signs. Rabies virus has not been isolated from skunk musk (spray).

The incubation period is both prolonged and variable; typically, the virus remains at the inoculation site for a considerable time. The unusual length of the incubation period helps to explain how postexposure treatment, including in humans the practice of locally infiltrating hyperimmune serum, is effective. Most cases in dogs develop within 21-80 days after exposure, but the incubation period may be shorter or considerably longer. One reliably recorded case of rabies in a human had an incubation period >6 yr.

The virus travels via the peripheral nerves to the spinal cord and ascends to the brain. After reaching the brain, the virus travels via peripheral nerves to the salivary glands. If an animal is capable of transmitting rabies via its saliva, virus will be detectable in the brain. Virus is shed intermittently in the brain.

Hematogenous spread does not occur. Under most circumstances, there is no danger of aerosol transmission of rabies. However, aerosol transmission has occurred under very specialized conditions in which the air contains a high concentration of suspended particles or droplets carrying viral particles. Such conditions have been responsible for laboratory transmission under less than ideal containment situations. There has also documented aerosol transmission in 1 bat cave. Oral and nasal secretions containing virus were probably aerosolized from tens of millions of bats. Aerosol infection may occur via direct attachment of the virus to olfactory nerve endings.

Clinical Findings:

Clinical signs of rabies are rarely definitive. Rabid animals of all species usually exhibit typical signs of CNS disturbance, with minor variations among species. The most reliable signs, regardless of species, are acute behavioral changes and unexplained progressive paralysis. Behavioral changes may include sudden anorexia, signs of apprehension or nervousness, irritability, and hyperexcitability (including priapism). The animal may seek solitude. Ataxia, altered phonation, and changes in temperament are apparent. Uncharacteristic aggressiveness may develop—a normally docile animal may suddenly become vicious. Commonly, rabid wild animals may lose their fear of humans, and species that are normally nocturnal may be seen wandering about during the daytime.

The clinical course may be divided into 3 phases—prodromal, excitative, and paralytic/endstage. However, this division is of limited practical value because of the variability of signs and the irregular lengths of the phases. During the prodromal period, which lasts ~1-3 days, animals show only vague CNS signs, which intensify rapidly. The disease progresses rapidly after the onset of paralysis, and death is virtually certain. Some animals die rapidly without marked clinical signs.

The term “furious rabies” refers to animals in which aggression (the excitative phase) is pronounced. “Dumb or paralytic rabies” refers to animals in which the behavioral changes are minimal, and the disease is manifest principally by paralysis.

Furious Form:

This is the classic “mad-dog syndrome,” although it may be seen in all species. There is rarely evidence of paralysis during this stage. The animal becomes irritable and, with the slightest provocation, may viciously and aggressively use its teeth, claws, horns, or hooves. The posture and expression is one of alertness and anxiety, with pupils dilated. Noise invites attack. Such animals lose caution and fear of other animals. Carnivores with this form of rabies frequently roam extensively, attacking other animals, including people, and any moving object. They commonly swallow foreign objects, eg, feces, straw, sticks, and stones. Rabid dogs may chew the wire and frame of their cages, breaking their teeth, and will follow a hand moved in front of the cage, attempting to bite. Young pups can seek human companionship and are overly playful, but bite even when petted, usually becoming vicious in a few hours. Rabid skunks may seek out and attack litters of puppies or kittens. Rabid domestic cats and bobcats can attack suddenly, biting and scratching viciously. As the disease progresses, muscular incoordination and seizures are common. Death results from progressive paralysis.

Paralytic Form:

This is first manifest by paralysis of the throat and masseter muscles, often with profuse salivation and inability to swallow. Dropping of the lower jaw is common in dogs. Owners frequently examine the mouth of dogs and livestock searching for a foreign body or administer medication with their bare hands, thereby exposing themselves to rabies. These animals may not be vicious and rarely attempt to bite. The paralysis progresses rapidly to all parts of the body, and coma and death follow in a few hours.

Species Variations:

Cattle with furious rabies can be dangerous, attacking and pursuing humans and other animals. Lactation ceases abruptly in dairy cattle. The usual placid expression is replaced by one of alertness. The eyes and ears follow sounds and movement. A common clinical sign is a characteristic abnormal bellowing, which may continue intermittently until shortly before death.

Horses and mules frequently show evidence of distress and extreme agitation. These signs, especially when accompanied by rolling, may be interpreted as evidence of colic. As in other species, horses may bite or strike viciously and, because of their size and strength, become unmanageable in a few hours. People have been killed outright by such animals. These animals frequently suffer self-inflicted wounds.

Rabid foxes and coyotes often invade yards or even houses, attacking dogs and people. The abnormal behavior that can occur is demonstrated by the fox that attacks a porcupine; finding a fox with porcupine quills can, in most cases, support a diagnosis of rabies.

Rabid raccoons and skunks typically show no fear of humans and are ataxic, frequently aggressive, and active during the day, despite their often crepuscular nature. In urban areas, they may attack domestic pets.

In general, rabies should be suspected in terrestrial wildlife acting abnormally. The same is true of bats that can be seen flying in the daytime, resting on the ground, attacking people or other animals, or fighting.

Rodents and lagomorphs rarely constitute a risk for rabies exposure. However, each incident must be evaluated individually. Reports of laboratory-confirmed rabies in woodchucks are not uncommon in association with the raccoon rabies epizootic in the eastern USA.

Diagnosis:

Clinical diagnosis is difficult, especially in areas where rabies is uncommon and should not be relied on when making public health decisions. In the early stages, rabies can easily be confused with other diseases or with normal aggressive tendencies. Therefore, when rabies is suspected and definitive diagnosis is required, laboratory confirmation is indicated. Suspect animals should be euthanized and the head removed for laboratory shipment.

Rabies testing should be done by a qualified laboratory, designated by the local or state health department in accordance with established national standardized protocols for rabies testing. Immunofluorescence microscopy on fresh brain tissue, which allows direct visual observation of a specific antigen-antibody reaction, is the test of choice. When properly used, it can establish a highly specific diagnosis within a few hours. Brain tissues examined must include medulla oblongata and cerebellum (and should be preserved by refrigeration with wet ice or cold packs). The mouse inoculation test or tissue culture techniques using mouse neuroblastoma cells may be used for indeterminate fluorescent antibody results, but it is no longer in common use in the USA.

Control:

Comprehensive guidelines for control in dogs have been prepared by the World Health Organization and include the following: 1) notification of suspected cases, and euthanasia of dogs with clinical signs and dogs bitten by a suspected rabid animal; 2) reduction of contact rates between susceptible dogs by leash laws, dog movement control, and quarantine; 3) mass immunization of dogs by campaigns and by continuing vaccination of young dogs; 4) stray dog control and euthanasia of unvaccinated dogs with low levels of dependency on, or restriction by, humans; and 5) dog registration.

The Compendium of Animal Rabies Control, compiled and updated annually by the National Association of State Public Health Veterinarians (NASPHV), summarizes the most current recommendations for the USA and lists all USDA-licensed rabies vaccines that are marketed in the USA. Many effective vaccines, such as modified-live virus, recombinant, and inactivated types, are available for use throughout the world; in the USA, no modified-live rabies virus vaccines are currently marketed (for any species). Recommended vaccination frequency is every 3 yr, after an initial series of 2 vaccines 1 yr apart. Several vaccines are also available for use in cats, and a few for use in ferrets, horses, cattle, and sheep. Because of the increasing importance of rabies in cats, vaccination of cats is extremely important. No vaccine is approved for use in wildlife kept as pets (including wolf hybrids), and protective immunity from the commercially available vaccines for domestic species has not been demonstrated in these species.

Until recently, the control of rabies in wildlife populations relied on the destruction of wildlife in an attempt to reduce the contact rate between susceptible animals; however, this proved difficult and often not publicly acceptable or effective. In Europe and Canada, use of oral vaccines distributed in baits to control fox rabies is widespread and effective. The disease in foxes has been eliminated from most of western Europe and curtailed significantly in Ontario. Use of a vaccinia-rabies glycoprotein recombinant virus vaccine in the USA has successfully controlled coyote rabies in southern Texas and appears to be limiting the western expansion of raccoon rabies from the eastern USA. The USDA license limits use of the vaccine to state or federal rabies programs; it is not available to private veterinarians or for individual animal use. It is also being used to assist in the control of dog rabies in developing countries.

Management of Suspected Rabies Cases—Exposure of Pets:

Where terrestrial wildlife or bat rabies is known to occur, any animal bitten or otherwise exposed by a wild, carnivorous mammal (or a bat) not available for testing should be regarded as having been exposed to rabies. The NASPHV recommends that any unvaccinated dog, cat, or ferret exposed to rabies be euthanized immediately. If the owner is unwilling to do this, the animal should be placed in strict isolation (ie, no human or animal contact) for 6 mo and vaccinated against rabies 1 mo before release. If an exposed animal is currently vaccinated, it should be revaccinated immediately and closely observed for 45 days.

Zoonotic Risk:

When a person is exposed to an animal suspected of having rabies, the risk of rabies transmission should be evaluated carefully. Risk assessment should include consideration of the species of animal involved, the prevalence of rabies in the area, whether exposure sufficient to transmit rabies occurred, and the current status of the animal and its availability for diagnostic testing. Wild carnivores and bats present a considerable risk where the disease is found, regardless of whether abnormal behavior has been observed. Insectivorous bats, though small, can inflict a wound with their teeth and should never be caught or handled with bare hands. Because bat bites often go unnoticed, direct contact with bats could be considered a risk for exposure. Any wild carnivore or bat suspected of exposing a person to rabies should be considered rabid unless proved otherwise by laboratory testing; this includes bats found in rooms with sleeping or otherwise unaware persons. Although some people make “pets” of wildlife, if one of those animals exposes a human or domestic animal, the wild animal should be managed like free-ranging wildlife. Any healthy domestic dog, cat, or ferret, whether vaccinated against rabies or not, that exposes (bites or deposits saliva in a fresh wound or on a mucous membrane) a person should be confined for 10 days; if the animal develops any signs of rabies during that period, it should be euthanized and its brain promptly submitted for rabies diagnosis. If the dog, cat, or ferret responsible for the exposure is stray or unwanted, it may be euthanized as soon as possible and submitted for rabies diagnosis. Since the advent of testing by immunofluorescence microscopy, there is no value in holding such animals to “let the disease progress” as an aid to diagnosis.

Pre-exposure immunization is strongly recommended for all people in high-risk groups, such as veterinary staff, animal control officers, rabies and diagnostic laboratory workers, and travelers working in countries in which canine rabies is endemic or epizootic. Vaccine is administered on days 0, 7, and 21 or 28. However, pre-exposure prophylaxis cannot be absolutely relied on in the event of subsequent rabies exposure and must be supplemented by a limited postexposure regimen (2 doses of vaccine IM on days 0 and 3).