Rabies PDF - A Comprehensive Guide

Rabies Importance Rabies is a neurological disease of mammals that is almost invariably fatal once the clinical signs develop. Humans are usually infected when they are bitten by an Hydrophobia, Lyssa inf...

Rabies Importance Rabies is a neurological disease of mammals that is almost invariably fatal once the clinical signs develop. Humans are usually infected when they are bitten by an Hydrophobia, Lyssa infected animal, or exposed to its saliva or central nervous system (CNS) tissues. Although rabies is generally well controlled among domesticated animals in Last Updated: October 2009 developed nations, canine rabies continues to be a serious problem in some areas of Africa, the Middle East, Asia and Latin America. Wildlife reservoirs have become increasingly important where canine rabies is under control. Rabies can be effectively treated if the exposure is recognized before the symptoms develop. However, people in impoverished countries do not always have access to post-exposure prophylaxis, and even in nations with good medical care, cases occur occasionally in people who do not realize they were exposed. Etiology Rabies results from infection by the rabies virus, a neurotropic virus in the genus Lyssavirus, family Rhabdoviridae. It is classified as genotype 1, serotype 1 in this genus. There are many strains of the rabies virus; each strain is maintained in particular reservoir host(s). Although these viruses can readily cause rabies in other species, they usually die out during serial passage in species to which they are not adapted. The reservoir host is sometimes used as an adjective to describe a strain’s origin. For example, if a virus from a skunk caused rabies in a dog, it would be described as skunk rabies in a dog, whereas a virus that is maintained in dog populations would be called canine rabies. Occasionally, a virus adapted to one species becomes established in another species. In the United States, skunk populations have been infected with raccoon and bat rabies variants, and canine rabies has become established in some populations of wild animals, such as gray foxes in Texas and Arizona. Closely related lyssaviruses, which are known as rabies-related lyssaviruses or nonrabies lyssaviruses, can cause a neurological disease that is identical to rabies. Lagos bat virus (genotype 2, serotype 2) is found in bats in parts of Africa, and has caused fatal cases of neurological disease in cats, dogs and a water mongoose (Atilax paludinosis). Some of these cats and dogs had been vaccinated against rabies. Mokola virus (genotype 3, serotype 3) is the only rabies-related lyssavirus that has not been found in bats. This virus has been isolated from rodents and shrews in Africa, but its reservoir host is unknown. It has caused fatal neurological disease in cats, dogs and humans, including rabies-vaccinated cats and dogs. Antibodies to Mokola virus have been reported in some healthy animals, and one child who might have been infected with this virus recovered. Duvenhage virus (genotype 4, serotype 4) occurs among bats in Africa. It has caused fatal rabies-like disease in several people. The European bat lyssaviruses (EBLV) are very similar to the Duvenhage virus, but are found in continental Europe. They are serotype 5 and are subdivided into 2 biotypes, EBLV1 (genotype 5) and EBLV2 (genotype 6). Clinical cases have been reported in animals (sheep, a stone marten) and humans. The Australian bat lyssavirus (ABLV; genotype 7) has been isolated in Australia. It has also been reported from humans with fatal rabies-like disease. Rabies and the rabies-related lyssaviruses have been classified into 2 phylogroups, based on how closely they are related. Phylogroup I contains the rabies virus, Duvenhage virus, EBLV1, EBLV2 and Australian bat virus, while phylogroup II consists of Lagos bat virus and Mokola virus. Four additional Eurasian bat viruses have also been tentatively classified as lyssaviruses. They include Irkut virus, Aravan virus and Khujand virus, which all belong to phylogroup I, and West Caucasian bat virus. Unless otherwise specified, the information in this outline refers to the classical rabies virus. Geographic Distribution With some exceptions (particularly islands), the rabies virus is found worldwide. Some countries including the United Kingdom, Ireland, Sweden, Norway, Iceland, Japan, Australia, New Zealand, Singapore, most of Malaysia, Papua New Guinea, the Pacific Islands and some islands in Indonesia have been free of the classical rabies RABS_H2009 © 2009 CFSPH page 1 of 9  Rabies virus for many years. According to the World Health The dissemination of the rabies virus within Organization (WHO), a country is considered to be free of the body rabies if there have been no indigenously acquired cases Immediately after infection, the rabies virus enters an in humans or animals during the previous 2 years, in the eclipse phase during which it is not easily detected. presence of adequate surveillance and import regulations. During this phase, it replicates in non-nervous tissue such Using this definition, several additional countries are as muscle. It does not usually stimulate an immune considered to be free of rabies. In some cases, these response at this time, but it is susceptible to neutralization nations have conducted rabies vaccination programs in if antibodies are present. After several days or months, the wildlife, but are susceptible to the reintroduction of the virus enters the peripheral nerves and is transported to the virus from neighboring countries. Official lists should be central nervous system by retrograde flow in the axons. consulted for the current list of rabies-free countries and After dissemination within the CNS, where clinical signs areas, as it may change. For example, rabies was develop as the neurons are infected, the virus is recently introduced into the island of Bali (Indonesia), distributed to highly innervated tissues via the peripheral which had been free of rabies for many years. nerves. Most of the virus is found in nervous tissue, The presence of the rabies-related lyssaviruses does salivary glands, saliva and cerebrospinal fluid (CSF), not prevent a nation from being listed as rabies-free. For which should all be handled with extreme caution. example, European bat lyssaviruses have been isolated Some virus has also been detected in other tissues from bats and a human with neurologic disease in the and organs, including the lungs, adrenal glands, kidneys, United Kingdom. Other countries considered to be rabies- bladder, heart, ovaries, testes, prostate, pancreas, free, such as Australia, also contain rabies-related intestinal tract, cornea, germinal cells of hair follicles in lyssaviruses. These viruses have not been reported from the skin, sebaceous glands, tongue papillae and the brown the Americas. fat of bats. The rabies virus is contained within the neurons, and handling most body fluids or intact organs is Transmission thought to carry a low risk of infection. However, a The rabies virus is readily transmitted between puncture could theoretically pierce a neuron, and health mammals, whether they are the same or different species. care personnel are given post-exposure prophylaxis after a This virus is usually spread in the saliva, when an infected needlestick or other puncture wound received while animal bites another. Less often, an animal or person is caring for a rabies patient. Organ transplants also pose a infected by contact with infectious saliva or neurological (rare) risk, if the donor is not known to have been infected tissues, through mucous membranes or breaks in the skin. with rabies. Blood, urine and feces are not thought to be The rabies virus is not transmitted through intact skin. infectious; however, a few studies have suggested that There are also rare reports of transmission by other viremia might occur at some point during the infection. A routes. A few cases have been reported after transplantation recent study in mice, using a polymerase chain reaction of organs, particularly corneas but also pancreas, kidneys (PCR) assay, found viral RNA in mice when they were and liver. Aerosol transmission has been documented in clinically ill, but not during the asymptomatic stage when special circumstances, such as in laboratories and bat caves virus was migrating to the CNS. with an unusually high density of aerosolized, viable virus Epidemiological cycles particles. Rabies viruses have been transmitted by ingestion in experimentally infected animals, and there is anecdotal Rabies is maintained in two epidemiological cycles, evidence of transmission in milk to a lamb and a human one urban and one sylvatic. In the urban rabies cycle, infant. (More conventional routes of spread could not be dogs are the main reservoir host. This cycle predominates ruled out in the latter case.) There is some speculation that in areas of Africa, Asia, and Central and South America ingestion could play a role in rabies transmission among where the proportion of unvaccinated and semi-owned or wild animals. One epizootic among kudu may have stray dogs is high. It has been virtually eliminated in spread between animals when they fed on thorn trees. North America and Europe; although sporadic cases occur There are no records of human disease acquired by this in dogs infected by wild animals, the urban cycle is not route. Nevertheless, in 2 incidents investigated by the perpetuated in the canine population. U.S. Centers for Disease Control and Prevention (CDC), The sylvatic (or wildlife) cycle is the predominant people who drank unpasteurized milk from rabid cows cycle in Europe and North America. It is also present were given post-exposure prophylaxis. Pasteurized milk simultaneously with the urban cycle in some parts of the and cooked meat are not expected to pose a risk of world. The epidemiology of this cycle is complex; factors infection, as the rabies virus is inactivated by heat; affecting it include the virus strain, the behavior of the however, as a precaution, the National Association of host species, ecology and environmental factors. In any State Public Health Veterinarians recommends against ecosystem, often one and occasionally up to 3 wildlife consuming tissues and milk from rabid animals. species are responsible for perpetuating a particular strain of rabies. The disease pattern in wildlife can either be Last Updated: October 2009 © 2009 CFSPH page 2 of 9  Rabies relatively stable, or occur as a slow moving epidemic. to carry the virus. A few cases of transmission have been Recent examples of epidemics include a fox rabies reported in corneal transplants or transplanted internal epidemic that moved slowly west in Europe, and a organs. raccoon rabies epidemic that moved north along the east coast of the U.S. and into Canada. Diagnostic Tests Antemortem diagnosis may include the detection of Disinfection antigens or nucleic acids, virus isolation or serology. RT- The rabies virus can be inactivated by lipid solvents PCR or immunofluorescence may detect viral nucleic (soap solutions, ether, chloroform, acetone), 1% sodium acids or antigens in saliva, or in skin biopsies taken from hypochlorite, 2% glutaraldehyde, 45-75% ethanol, iodine the nape of the neck. In skin, the virus occurs in the preparations, quaternary ammonium compounds, cutaneous nerves at the base of the hair follicles. Rabies formaldehyde or a low pH. This virus is also susceptible to virus is sometimes found in corneal impressions or eye ultraviolet radiation or heat of 1 hour at 50°C. It is rapidly wash fluid, and RT-PCR may occasionally detect nucleic inactivated in sunlight, and it does not survive for long acids in CSF. Virus isolation is helpful in either periods in the environment except in a cool dark area. antemortem or postmortem diagnosis. Rabies virus can sometimes be isolated from the saliva, conjunctival Infections in Humans secretions/tears, corneal impressions, skin biopsies or (less often) CSF in living patients, and from the brain at Incubation Period autopsy. Mouse neuroblastoma (MNA) cells and other In humans, the incubation period is a few days to cell lines can be used to recover the virus. Animal several years. Most cases become apparent after 1 to 3 inoculation into weanling mice may also be done. More months. In one study, approximately 4-10% of cases had than one test is usually necessary for an antemortem an incubation period of 6 months or more. diagnosis, as the virus is not invariably present in any tissue other than the CNS. Rabies is usually undetectable Clinical Signs during the incubation period, and infections can also be The early symptoms may include nonspecific difficult to diagnose when the clinical signs first appear. prodromal signs such as malaise, fever or headache, as In some cases, rabies virus cannot be isolated even when well as discomfort, pain, pruritus or sensory alterations at antigens or nucleic acids are detected by other methods. the site of virus entry. After several days, anxiety, Postmortem diagnosis is usually by immunofluorescence confusion and agitation may appear, and progress to to detect viral antigens in the brain. insomnia, abnormal behavior, hypersensitivity to light and Serological tests include indirect immuno- sound, delirium, hallucinations, slight or partial paralysis, fluorescence, virus neutralization and enzyme-linked hypersalivation, difficulty swallowing, pharyngeal spasms immunosorbent assay (ELISA), and can be performed on upon exposure to liquids, and convulsions. Either an serum or CSF. The detection of antibodies in the CSF is encephalitic (furious) form with hyperexcitability, definitive; however, antibodies in the serum might also autonomic dysfunction and hydrophobia, or a paralytic result from vaccination or the administration of human (dumb) form characterized by generalized paralysis, may rabies immunoglobulin. Circulating neutralizing predominate. Death usually occurs within 2 to 10 days; antibodies do not usually appear until late, and infected survival is extremely rare. people may still be seronegative when they die. Communicability Treatment Human saliva contains the rabies virus; person-to- Postexposure prophylaxis consists of immediate person transmission is theoretically possible but rare. wound cleansing and disinfection, followed by rabies Activities that could pose a risk for exposure include vaccination and the administration of human rabies bites, kisses or other direct contact between saliva and immunoglobulin. The rabies vaccine is given as 5 doses in mucous membranes or broken skin, sexual activity, and the U.S., and it is usually administered intramuscularly in sharing eating or drinking utensils or cigarettes. It is not the arm. Fewer doses and no rabies immunoglobulin are known how long humans can shed the virus before given if the person was previously vaccinated. becoming symptomatic; the CDC recommends post- Postexposure prophylaxis is highly effective if it is begun exposure prophylaxis for anyone who had at-risk contact soon after exposure. with a person during the 14 days before the onset of There is no effective treatment once the symptoms clinical signs. develop. Vaccines, antiviral drugs such as ribavirin, The CDC also recommends prophylactic treatment interferon-alpha, passively administered anti-rabies virus after a needlestick or other sharp object injury during an antibodies (human immunoglobulin or monoclonal autopsy or during patient care, due to the possibility that antibodies), ketamine and/or the induction of a coma have the object could have passed through nervous tissue. been tried in the past, but were usually ineffective. Feces, blood, urine and other body fluids are not thought Last Updated: October 2009 © 2009 CFSPH page 3 of 9  Rabies Treatment is often palliative, and there is a very high exposed or, for some other reason, did not seek medical probability of an unsuccessful outcome. One patient who treatment. Post-exposure prophylaxis, begun promptly, recovered well was treated with ribavirin and supportive is almost always successful. Human rabies is also rare in care including the induction of a therapeutic coma; Canada, most European countries, and some countries in however, the same treatment protocol has been South America. The prevalence rates are high in some unsuccessful in other patients. If treatment is successful in parts of the developing world. Worldwide, over 90% of sustaining life, there may be permanent and possibly rabies cases occur after exposure to rabid dogs. In severe neurologic defects. countries with a high percentage of vaccinated dogs, they are much less important as a vector, and wildlife Prevention such as bats account for a higher percentage of the cases. Domesticated animals (especially dogs, cats and Factors that may affect the outcome of exposure ferrets) should be vaccinated to prevent them from include the virus variant, dose of the virus, route and becoming infected and transmitting rabies to humans. location of exposure, and host factors such as age and Stray animals should also be controlled. Dogs, in immune status. Without post-exposure prophylaxis, an particular, act as reservoirs for a canine variant of the estimated 20% of people bitten by rabid dogs develop rabies virus. Cats are readily infected by rabies, but a cat- rabies. Once the symptoms appear, the disease is almost specific variant does not occur in feline populations. Wild always fatal within 3 weeks, even with intensive care. animals should not be handled or fed; wildlife behaving There have been only 6 reported cases of survival abnormally should particularly be avoided. Bats should be through the acute illness. Two people recovered well, kept out of houses and public buildings. In some areas, without severe neurological sequelae. Both of these wild animals are vaccinated orally, using baits. people had antibodies to the rabies virus at the time of Veterinarians and animal control officers should the diagnosis, and diagnostic tests based on the detection handle potentially rabid animals with extreme caution. of the virus were negative. Four survivors were left with Protective clothing such as thick rubber gloves, eye severe neurological complications. Five survivors had goggles and a plastic or rubber apron should be worn been treated with a rabies vaccine before or soon after when doing autopsies or in other circumstances when exposure, and before the symptoms developed. One exposure to infectious tissues could occur. young girl (who survived and recovered well) received Bites or other exposures should be reported no rabies prophylaxis because she had rabies virus- immediately. Post-exposure prophylaxis consists of neutralizing antibodies at diagnosis. Some survivors immediate wound cleansing and disinfection, rabies might have had post-vaccinal encephalomyelitis rather vaccination and the administration of human rabies than rabies. immunoglobulin. Asymptomatic dogs, cats or ferrets that have bitten humans are observed for 10 days; if the Infections in Animals animal develops symptoms of rabies during this time, it is euthanized and tested for rabies. Species Affected An inactivated human vaccine is available for All mammals are susceptible to rabies. There are veterinarians, animal handlers, wildlife officers, many strains of the rabies virus; each strain is maintained laboratory workers and others at a high risk of exposure. in particular reservoir host(s). Important maintenance International travelers may also be vaccinated in some hosts include members of the Canidae (dogs, jackals, cases. People who have been vaccinated must still receive coyotes, wolves, foxes and raccoon dogs), Mustelidae post-exposure prophylaxis, but vaccination eliminates the (skunks, martens, weasels and stoats), Viverridae requirement for rabies immunoglobulin and decreases the (mongooses and meerkats), and Procyonidae (raccoons), number of post-exposure vaccinations. It may also and the order Chiroptera (bats). Cat-adapted rabies provide some protection for persons with inapparent variants have not been seen, although cats are often exposure, or enhance immunity if postexposure infected with rabies viruses from other hosts, and they can prophylaxis is delayed. Rabies vaccines seem to provide readily transmit the virus. some degree of cross-protection against rabies-related The important reservoir hosts vary with the area. In lyssaviruses in phylogroup I, but there is little or no cross- North America, maintenance hosts for rabies virus protection with the viruses in phylogroup II (Mokola virus include insectivorous bats, striped skunks (Mephitis and Lagos bat virus). The amount of protection against mephitis), raccoons (Procyon lotor) coyotes (Canis phylogroup I viruses may vary with the specific virus. latrans) and various species of foxes. Red foxes (Vulpes vulpes), insectivorous bats, wolves and raccoon dogs Morbidity and Mortality (Nyctereutes procyonoides) appear to be important hosts In the U.S., clinical rabies is rare in humans, with in Europe. The canine rabies variant is well controlled in 0-3 cases usually reported each year. Deaths are usually the U.S., Canada and Europe, and it may no longer be reported in people who did not realize they had been circulating or circulates only at low levels in some areas. Last Updated: October 2009 © 2009 CFSPH page 4 of 9  Rabies However, this virus has apparently become established uncommon. Death usually occurs within 2 to 6 days, as the in some wildlife populations, such as gray foxes result of respiratory failure. (Urocyon cinereoargenteus) in Texas and Arizona, and it The furious form is associated with infection of the could be re-established in dogs from these reservoirs. limbic system, and is the predominant form in cats. It is Canine rabies continues to be a significant problem characterized by restlessness, wandering, howling, in areas of Africa, Asia, the Middle East, and Latin polypnea, drooling and attacks on animals, people or America. Wildlife hosts may also be present. Both inanimate objects. Animals with this form often swallow insectivorous and vampire bats are hosts for rabies virus foreign objects such as sticks, stones, straw or feces. Wild in Mexico, Central and South America. Vampire bats animals often lose their fear of humans, and may attack (Desmodus rotundus) are sometimes responsible for humans or animal species they would normally fear (e.g., outbreaks among cattle in South America. Rabies has also porcupines). Nocturnal animals may be seen in the been reported in various other wildlife species, including daylight. Cattle may appear unusually alert. Convulsions wolves, coyotes, skunks and foxes, in Central and South can occur, particularly in the terminal stages. In the America. Red foxes and golden jackals (Canis aureus) furious form of rabies, death sometimes occurs during a are often involved in wildlife rabies in the Middle East. seizure but, in most cases, incoordination and ascending Red and arctic foxes, raccoon dogs, mongooses and paralysis are seen late in the disease. The animal usually jackals are hosts for the virus in parts of Asia. dies 4 to 8 days after the onset of the clinical signs. Mongooses are also important in the Caribbean. In The clinical signs are rarely definitive, and it may be Africa, there is evidence that the virus may be difficult to distinguish the furious and dumb forms. The maintained in jackals, foxes, mongooses, genets and most reliable signs are behavioral changes and other species. unexplained paralysis. In some cases in cats, no behavioral changes were noticed, and the illness appeared Incubation Period to begin as ataxia or posterior weakness, followed by The incubation period varies with the amount of ascending paralysis. Horses and mules are often distressed virus transmitted, virus strain, site of inoculation (bites and extremely agitated, which may be interpreted as colic. closer to the head have a shorter incubation period), host Laryngeal paralysis can cause a change in vocalizations, immunity and nature of the wound. In dogs and cats, the including an abnormal bellow in cattle or a hoarse incubation period is 10 days to 6 months; most cases howling in dogs. Diagnosis can be difficult in rabbits and become apparent between 2 weeks and 3 months. In rodents unless there is a history of exposure to a cattle, an incubation period from 25 days to more than 5 potentially rabid animal, such as a raccoon. Some infected months has been reported in vampire bat-transmitted rabbits have had obvious neurological signs, often of the rabies. paralytic form, but others have developed only a Clinical Signs nonspecific illness before death, or had other signs that were not initially suggestive of rabies. In one report, The initial clinical signs are often nonspecific and may sudden death was the only sign in many infected squirrels. include apprehension, restlessness, anorexia or an increased Some animals may die within a day, without marked appetite, vomiting, a slight fever, dilation of the pupils, clinical signs. Survival is extremely rare once the clinical hyperreactivity to stimuli and excessive salivation. The first signs appear. sign of post-vaccinal rabies is usually lameness in the vaccinated leg. Animals often have behavior and Communicability temperament changes, and may either become unusually All species can transmit the virus to humans and other aggressive or uncharacteristically affectionate. Pigs animals, but the efficiency of transmission varies with the typically have a very violent excitation phase at the onset of host species and the form of rabies. Animals with the disease. These signs usually last for 2 to 5 days, and may be furious form of rabies are more likely to disseminate rabies followed by a phase in which either the paralytic or the than animals with the paralytic form. Carnivores are also furious form of rabies predominates. more efficient vectors, in general, than herbivores. The paralytic (“dumb”) form of rabies is characterized Herbivore-to-herbivore transmission is uncommon. by progressive paralysis. In this form, the throat and Insectivorous bats have been implicated in most recent masseter muscles become paralyzed; the animal may be human cases in the U.S. unable to swallow and it can salivate profusely. There may Virus shedding occurs in 50-90% of animals, be facial paralysis or the lower jaw may drop. Ruminants depending on the host species and the infecting strain; the may separate from the herd, become somnolent or amount of virus found in the saliva varies from a trace to depressed, and rumination may stop. Ataxia, incoordination high titers. Shedding can begin before the onset of clinical and ascending spinal paresis or paralysis are also typical of signs. Cats excrete virus for 1 to 5 days before the signs this form. The paralytic form of rabies may be preceded by appear, cattle for 1 to 2 days, skunks for up to 14 days and a brief excitatory phase, or none at all. Biting is bats for 2 weeks. Virus shedding in dogs is usually said to Last Updated: October 2009 © 2009 CFSPH page 5 of 9  Rabies be limited to the 1 to 5 days before the onset of clinical Treatment signs; however, in some experimental studies (using There is no treatment once the clinical signs viruses of Mexican or Ethiopian origin), the virus was appear. Few studies have been published on post- present in the saliva for up to 13 days before the first exposure vaccination protocols for animals, and these clinical signs. procedures are often considered to be inadvisable Asymptomatic carriers are thought to be very rare because they may increase human exposure. In the among domesticated animals. Possible cases have been U.S., post-exposure prophylaxis of animals has not reported among dogs in Ethiopia and India, including one been validated and is not recommended. Post-exposure experimentally infected dog that recovered from clinical prophylaxis of livestock and pets, using commercial rabies and carried the virus in her saliva and tonsils, but vaccines licensed for this purpose, is practiced in some not the brain or other organs. Asian countries including India. Post-Mortem Lesions Prevention There are no characteristic gross lesions. The stomach Rabies can be prevented in domesticated animals by may contain various abnormal objects, such as sticks and vaccination and by the avoidance of contact with rabid stones. The typical histological signs, found in the central wild animals. Rabies vaccines are available for dogs, cats, nervous system, are multifocal, mild, polioencephalo- ferrets, cattle, sheep and horses. Both inactivated and myelitis and craniospinal ganglionitis with mononuclear modified live vaccines are effective, but rare cases of perivascular infiltrates, diffuse glial proliferation, post-vaccinal rabies have been reported with the modified regressive changes in neuronal cells, and glial nodules. live vaccines in dogs and cats. Vaccines have not been Negri bodies can be seen in some but not all cases. validated in rabbits or rodents, although they might be used extralabel in petting zoos or other facilities where Diagnostic Tests animals are in contact with many people. Wild animals In animals, the rabies virus is usually identified by can be immunized with oral vaccines distributed in bait. immunofluorescence in a brain sample taken at necropsy. In countries with large stray dog populations, similar The virus might also be found in other tissues such as the vaccines may be useful. Conventional rabies vaccines do salivary gland, skin (tactile facial hair follicles) and not seem to protect animals against rabies-related viruses corneal impression smears, but detection is less efficient. in phylogroup II (Mokola virus and Lagos bat virus); Immunofluorescence can identify 98-100% of cases these viruses have caused fatal disease in vaccinated caused by all genotypes of the rabies and rabies-related animals. Some cross-protection seems to exist with viruses, and is most effective on fresh samples. Other rabies-related viruses in phylogroup I. tests to detect the virus include immunohistochemistry Preventing animals from roaming will reduce the risk and enzyme-linked immunosorbent assays (ELISAs). RT- of exposure to rabid wild animals. To protect pet rabbits PCR is also useful, particularly when the sample is small and rodents, they should be housed indoors, and watched (e.g., saliva) or when large numbers of samples must be closely if they are allowed outside to exercise. Rabbits tested in an outbreak or epidemiological survey. kept outside should be kept in an elevated, double-walled Histology to detect aggregates of viral material in neurons hutch that does not have exposed wire mesh floors. As (Negri bodies) is nonspecific, and it is not recommended much as possible, domesticated animals should be kept if more specific techniques are available. from contact with wildlife, especially those that behave A single negative test does not rule out infection; unusually. Bats caught by cats should be submitted for therefore, virus isolation in cell culture (mouse rabies testing. neuroblastoma or baby hamster kidney cells) is often done To prevent the transmission of rabies to humans or concurrently. Mouse inoculation may also be used in other animals (as well as to prevent unnecessary some circumstances. Identification of variant strains is prophylaxis in people who have been exposed), performed in specialized laboratories with monoclonal unvaccinated animals that have been exposed should be antibodies, specific nucleic acid probes, or RT-PCR euthanized and tested. Alternatively, they may be placed followed by DNA sequencing. in strict isolation for 6 months, with vaccination of dogs, Serology is occasionally used to test seroconversion cats and ferrets either upon entry into isolation or 1 in domesticated animals before international travel or in month before release. Livestock, rabbits and other wildlife vaccination campaigns. It is rarely useful for the animals are isolated but not necessarily vaccinated. diagnosis of clinical cases, as the host usually dies Vaccinated animals are revaccinated and confined under before developing antibodies. Serological tests include observation for at least 45 days. Animals with expired virus neutralization tests and ELISAs. There is some vaccinations are evaluated on a case-by-case basis. cross-reactivity between the rabies virus and rabies- Asymptomatic dogs, cats or ferrets that have bitten related viruses. humans (with no history of exposure to rabies) are currently observed for 10 days; if the animal develops Last Updated: October 2009 © 2009 CFSPH page 6 of 9  Rabies signs of rabies during this time, it is euthanized and World Health Organization tested for rabies. Countries free of the rabies virus may http://www.who.int/mediacentre/factsheets/fs099/en/ require a prolonged quarantine period before animals World Organization for Animal Health (OIE) can be imported. http://www.oie.int/ Morbidity and Mortality OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals Canine rabies remains common in Africa, Asia, the http://www.oie.int/eng/normes/mmanual/a_summry.htm Middle East and Latin America. In the U.S., Canada and Europe, canine rabies has become uncommon or is absent, OIE International Animal Health Code and most cases are seen in wildlife. In the U.S., 35% of all http://www.oie.int/eng/normes/mcode/A_summry.htm animal cases were reported in raccoons, 23% in skunks, 26% in bats and 7% in foxes in 2008. Domesticated References animals account for less than 10% of all cases Abelseth MK. Rabies. In: Holzworth J, editor. Diseases of documented annually in the U.S.; most cases are seen in the cat. 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