rabies

Pictures

Picture	Title	Caption	Copyright
Title Symptoms Caption Furious stage of rabies in cattle: Salivation, dropped lower jaw and strabismus can be seen on this highly excited rabid cow. Whilst pressing its head onto the fence it was producing a highly abnormal bellowing sound. Copyright Károly Vörös/Department of Internal Medicine, University of Veterinary Science, Budapest	Symptoms	Furious stage of rabies in cattle: Salivation, dropped lower jaw and strabismus can be seen on this highly excited rabid cow. Whilst pressing its head onto the fence it was producing a highly abnormal bellowing sound.	Károly Vörös/Department of Internal Medicine, University of Veterinary Science, Budapest
Title Symptoms Caption Rabies virus; Here, two dogs are afflicted with dumb rabies, manifested as depression and an attempt at self-imposed isolation. Domesticated animals afflicted with dumb rabies may become increasingly depressed, and try to hide in isolated places, while wild animals seem to lose their fear of human beings, often appearing unusually friendly. Copyright Public Domain - Released by the Centre for Disease Controls (CDC)	Symptoms	Rabies virus; Here, two dogs are afflicted with dumb rabies, manifested as depression and an attempt at self-imposed isolation. Domesticated animals afflicted with dumb rabies may become increasingly depressed, and try to hide in isolated places, while wild animals seem to lose their fear of human beings, often appearing unusually friendly.	Public Domain - Released by the Centre for Disease Controls (CDC)
Title Symptoms Caption Rabies virus; close up of a dog's face, showing symptoms of late paralytic rabies. USA. 1963. Copyright Public Domain - Released by the Centre for Disease Controls (CDC)/Barbara Andrews-1963	Symptoms	Rabies virus; close up of a dog's face, showing symptoms of late paralytic rabies. USA. 1963.	Public Domain - Released by the Centre for Disease Controls (CDC)/Barbara Andrews-1963

Identity

Preferred Scientific Name

• rabies

International Common Names

• English: dumb rabies; furious rabies; hydrophobia; lyssa; madness; paralytic rabies; rabies
• Spanish: rabia
• French: rage
• Russian: beshenstvo

Local Common Names

• Croatia: bjesnoce
• Germany: Tollwut
• Hungary: veszettség
• Italy: rabbia
• Poland: wscieklizna
• Portugal: raiva
• Slovakia: besnota
• Slovenia: stekline
• Yugoslavia (Serbia and Montenegro): bjesnoce

Overview

Rabies is caused by a neurotropic virus that is transmissible to all mammals. Birds are much less susceptible to the virus than mammals, and the presence of disease in them is very rare. The first description of rabies originates from Babylon (BC 2300). Later, Demokritos and Aristotle mentioned transmission by dogs (BC 500 and BC 400, respectively). Pasteur and his co-workers developed the first immunization method in 1885. Negri discovered the inclusion bodies named after him in 1903, and the immunofluorescence test for rabies was devised by Goldwasser and Kissling in 1958.

The importance of rabies is characterized by its worldwide distribution, fatal outcome and its zoonotic aspects. Although direct economic losses are low, costs of control and elimination of the disease from a region are very high.

This disease is on the list of diseases notifiable to the World Organisation for Animal Health (OIE). The distribution section contains data from OIE's WAHID database on disease occurrence. Please see the AHPC library for further information on this disease from OIE, including the International Animal Health Code and the Manual of Standards for Diagnostic Tests and Vaccines. Also see the website: www.oie.int.

Hosts/Species Affected

Hosts of infection can be any of the wild or domestic animals listed under the rabies virus data sheet. Ruminants, swine and horses kept outdoors under extensive husbandry systems are especially prone to infection.

Distribution

Rabies occurs throughout the world and only a few countries are free of the disease, due to successful eradication programs or to island status and enforcement of rigorous quarantine regulations (Aiello and Mais, 1998; Blancou, 1998). In farm animals, rabies occurs in cattle, sheep, pigs, and horses in most countries. Bovines, including cattle and buffaloes, are the most commonly affected domestic animals (Gylys et al., 1998; Jindal and Narang, 1998; Krebs et al., 1998). Rabies in cattle is a major economic and public health problem in South America, where vampire bat-transmitted rabies results in cyclic outbreaks (Alvarez-Peralta, 1997; Jacobo et al., 1998). In Europe, sylvatic rabies is a major problem where the red fox is the principal vector; cattle are mainly infected by rabid foxes (Pastoret and Brochier, 1999; Muller et al., 1999b). More recently, bat-transmitted rabies has also been described in Europe (WHO, 1996; World Health Organization, 1998). Rabies occurs in most countries in Africa, and affects cattle and other bovines. In USA, endemic infection exists throughout southern Ohio, and the prairie states; rabies in domestic animals has steadily decreased there during the past 30 years, whereas annual occurrence in wild animals has increased (Krebs et al., 1999). Rabies is widespread and is a serious problem in several countries in Asia (Rathore, 1998), and in both European and Asian Russia. Australia and New Zealand have never had the disease (Radostits et al., 1999).

For current information on disease incidence, see OIE's WAHID Interface.

Rabies is common and enzootic in many African countries. A total of 34 countries reported 1,608 outbreaks of rabies to AU-IBAR in 2011, accounting for 7.2% of all disease outbreaks reported making it the disease with the highest number of outbreak reports. By virtue of the reports received it would appear that rabies is the most widely distributed zoonotic disease in Africa. This observation should be tempered by the fact that other zoonotic diseases are less readily diagnosed on clinical signs alone and it can be argued that many cases of for example brucellosis, echinococcosis and cysticercosis go undetected and are consequently under-reported. Algeria, South Africa and Namibia recorded the highest number of outbreaks of brucellosis with 522, 236 and 183 reports respectively (AU-IBAR, 2011).

Countries in Africa reporting rabies to AU-IBAR in 2011

NS=Not specified 

Although rabies is one of the major zoonotic diseases, reports on its situation from many countries are often incomplete. There were many gaps in the reports received in 2011, most of which did not capture the number of outbreaks, cases, mortalities, species involvement, sources of infection and the number of human cases. These parameters are essential to substantiate the impact of rabies in public health. Nevertheless, available data calls for an urgent, concerted and coordinated effort in controlling the disease in Africa considering its impact on human health.

Dogs were the most commonly affected species, constituting 63% of all cases followed by cattle (16%) and sheep and goats (4%). There was a high incidence of rabies cases in wildlife reported by Namibia where 59 cases of a total of 70 reported cases occurred in wildlife. The species most commonly affected were the greater kudu antelope and jackal.

Distribution Table

The distribution in this summary table is based on all the information available. When several references are cited, they may give conflicting information on the status. Further details may be available for individual references in the Distribution Table Details section which can be selected by going to Generate Report.

Pathology

The virus travels via the peripheral nerves to the spinal cord and ascends to the brain after replication within muscle cells near the site of inoculation. After reaching the brain, the virus usually travels efferently through the peripheral nerves to the salivary glands (Aiello and Mais, 1998; Singh and Grewal, 1998a).

Macroscopic findings are unremarkable, and there is no gross pathognomonic lesion for rabies. Histopathological findings are characterized by non-suppurative encephalomyelitis and ganglioneuritis, with neuronal necrosis and the formation of glial nodules. Negri bodies (aggregates of viral material in the cytoplasm of neurones) are most commonly found in the Purkinje cells of the cerebellum in ruminants (Radostits et al., 1999).

Diagnosis

In any animal, the first sign is a change in behaviour, which may be indistinguishable from a gastrointestinal disorder, injury, foreign body in the mouth, poisoning, or an early infectious disease. Temperature change is not significant and drivelling may or may not be noted. Animals usually stop eating and drinking and may seek solitude. Frequently, the urogenital tract is irritated or stimulated as evidenced by frequent urination, erection in the male, and sexual desire. After the prodromal period of 1-3 days, animals either show signs of paralysis or become vicious. Paralysis of the cranial nerves is soon obvious and commonly results in difficulties in chewing, drinking, swallowing (dyspaghia), and evidence of drooling. Dropping of the lower jaw and strabismus can often be observed.

Signs may vary with the species affected (Kandavel et al., 1989; Aiello and Mais, 1998, Stoltenow et al., 1998; Vörös et al., 1999). Cattle with furious rabies are dangerous, attacking and pursuing man and other animals; instead of the usual placid expression there is one of alertness. A common clinical sign is a characteristic abnormal bellowing. In the paralytic form, cranial nerve paralysis, especially hind leg paresis followed by paralysis of all four legs may be observed, while excitement may be missing. Finally, recumbency and death will follow. The signs in sheep and goats resemble those in cattle. In sheep, vigorous wool pulling, tremors and sudden falling can occur; however, many sheep become quiet and anorectic. Infected goats are commonly aggressive, and continuous bleating is common. Rabid swine manifest excitement and a tendency to attack, or conversely, dullness and incoordination. Rapid chewing movements and convulsions can also be present. Paralysis and death usually occurs in pigs 12-48 hours after the onset of signs, which may be extremely variable (Hou, 1992; Kociorski, 1994).

Clinical observation may only lead to a suspicion of rabies, because symptoms of the disease are not always characteristic and may vary greatly from one animal to another.

Several diseases, especially those affecting the nervous system, can resemble some signs of rabies (Leupold et al., 1989). The following list includes examples for farm animals (Radostits et al., 1999).

Cattle, sheep and goats

Lead poisoning, lactation tetany, polioencephalomalacia (vitamin B1 hypovitaminosis), vitamin A deficiency, listeriosis, bacterial meningoencephalitis, pseudorabies (Aujeszky's disease in cattle), enterotoxemia in sheep, pregnancy ketosis in sheep, coenurosis in sheep.

Swine

Pseudorabies, Teschen's disease, African swine fever, bacterial meningoencephalitis.

As a golden rule, in regions where the disease is present, rabies should be considered in any cases with even uncertain nervous signs or in animals found in a moribund stage or dead in outside pens or pastures, until otherwise proven.

As there is no gross pathognomonic lesion for rabies, diagnosis can only be made by laboratory techniques, preferably conducted on central nervous system (CNS) tissue previously removed from the cranium; the hippocampus (Ammon's horn) and the medulla oblongata are the tissues of choice. However, similar laboratory methods can also be applied to other organs, such as the salivary glands and cornea (Singh et al., 1999). Specimens for rabies diagnosis must be processed rapidly and sent to the laboratory under cold conditions, because rabies virus can be soon inactivated by heat (Barrat, 1992).

Diagnosis is preferably performed using the fluorescent antibody test (FAT). A drop of immune serum previously conjugated with fluorescein isothiocyanate is added to a fixed brain tissue smear, preferably made from several parts of the brain including the hippocampus and medulla oblongata (Umoh and Blenden, 1981; Barnard and Voges, 1982; Barrat, 1992). Alternatively, antibody may be conjugated to an enzyme such as peroxidase instead of fluorescein isothiocyanate (FITC). This conjugate may be used for direct diagnosis with the same sensitivity as FAT (Genovese and Andral, 1978). The immunoenzyme technique can provide rapid results when handling a large number of samples as part of an epidemiological survey. This is 'rapid rabies enzyme immunodiagnosis' (RREID), an ELISA test that detects rabies antigen (Perrin et al., 1986). Both FAT and RREID provide a reliable diagnosis in 98-100% of cases.

Histological tests can be used to demonstrate infected neuronal cells. These traditional procedures will reveal aggregates of viral material (the Negri bodies) in the cytoplasm of neurones. Nevertheless, this method does not always detect the virus (Singh and Grewal, 1998b), and the sensitivity of histological techniques depends on the degree of autolysis of the specimen; up to 15% false-negative results are observed on putrefied specimens. As a single negative test on fresh material does not rule out the possibility of infection, inoculation tests should be carried out simultaneously. Newborn mice or 3-4-week-old mice are inoculated intracerebrally with a suspension of hippocampal tissue, or a pool of several CNS tissues, and then kept under observation for 28 days. For any mouse that dies between 5 and 28 days, the cause of death should be confirmed by FAT. A neuroblastoma cell line, identified CCL131 in the American Type Culture Collection (ATCC), is used as a cell culture test for routine diagnosis of rabies. This cell line is sensitive to street isolates, but should be checked for susceptibility to locally predominant virus variants before use. Replication of rabies virus in the cells is revealed by FAT (Barrat et al., 1986). This test is as sensitive as the mouse inoculation test, but it is much cheaper and gives a more rapid result.

Serological evidence of infection is rarely obtained because of the high mortality rate of host species, although such evidence may be used in some epidemiological surveys. However, serological tests are used to assess the potency of vaccines against rabies; these are the virus neutralization test and the fluorescent antibody virus neutralization (FAVN) tests (Smith et al., 1973; Zalan et al., 1979; Perrin et al., 1985).

List of Symptoms/Signs

Disease Course

The incubation period of naturally occurring cases is usually about 3 weeks, but can vary from 2 weeks to several months. Rabid animals of all species exhibit typical signs of central nervous system (CNS) disturbance, with minor variations peculiar to carnivores, ruminants, bats, and humans. The clinical course, particularly in dogs, can be divided into three phases: the prodromal, the excitative, and the paralytic. The term 'furious rabies' refers to animals in which the excitative phase is predominant, and 'dumb' or 'paralytic rabies' to those in which the excitative phase is extremely short or absent and the disease progresses quickly to the paralytic phase. The disease progresses rapidly after the onset of paralysis; death usually occurs within 3-6 days and is virtually certain within 10 days of the first signs (Tanyi et al., 1988; Schulz, 1989).

Epidemiology

The source of infection is always an infected animal, and the method of spread is almost always by the bite of an infected animal, although contamination of skin wounds by fresh saliva may result in infection. Aerosol transmission can occur under special circumstances, for example, in bat caves or in laboratories manipulating the virus. The virus may appear in the milk of infected animals, but spread by this means is not very likely. Animal vectors are numerous and their role differs according to region. Traditionally the dog, and to a lesser extent the cat, have been the main sources of infection in domestic settings. The native fauna provide the major sources of infection in countries where domestic or feral carnivores are well controlled (Muller et al., 1999). Cattle are rarely a source of infection, although transmission to humans may occur when manipulating the mouth of a rabid animal, for example, during treatment or examination (Tariq et al., 1991; Radostits et al., 1999).

Impact: Economic

Losses from diseased animals (which invariably all die) are relatively low (Borowka, 1994). Of more significance is the value of condemned milk from infected or possibly infected cows and the expenses of preventive vaccination of animals (World Health Organization, 1989, Dufour et al., 1989), and post-infection vaccination of people (Anon., 1999; Zeller et al., 1989).

Zoonoses and Food Safety

Rabies is transmissible to humans by the inoculation (via bites, mainly from carnivores, or wounds contaminated with saliva) or inhalation (from bats) of infectious virus. Rabies in humans produces very grave central nervous system (CNS) clinical signs (Krebs et al., 1999), and has a fatal outcome in nearly all cases. This very severe illness requires skilful intensive care with attention to the airway, maintenance of oxygenation, and control of seizures.

Post-infection control of the disease should be done by vigorous first aid for bite wounds and post-exposure immunization (Zeller et al., 1989; Ostrowska and Hermanowska-Szpakowicz, 1997). Therefore, local health authorities must be consulted in all cases of suspected exposure.

The milk and meat of infected animals should be condemned. People that have accidentally consumed infected products should be vaccinated against rabies; this may be an expensive operation (Borowka, 1994; Anon., 1999).

Disease Treatment

No treatment should be attempted after clinical signs are evident. Euthanasia of suspect animals must be avoided, particularly if human exposure has occurred, since the development of the disease in animals is necessary to establish a diagnosis (Radostits et al., 1999). In several countries, cases of rabies in farm animals are notifiable to the animal health and disease regulatory bodies.

Prevention and Control

Rabies vaccines for use in animals contain either live virus attenuated for the target species (for example, Flury low egg passage, Flury high egg passage, Street-Alabama-Dufferin or Kelev), or virus inactivated by chemical or physical means, or recombinant vaccines.

Subtypes of rabies virus may vary considerably in their pathogenicity. They can be classified according to origin as vulpine, canine, etc. However, with the exception of serotype 3, their immunogenicity provides almost complete cross-protection. For animals, live vaccines are also effective by the oral route and can be distributed in baits in order to immunize wild (or domestic) animals (Kieny et al., 1984, Krebs et al., 1999). Live recombinant vaccine (for example, vaccinia rabies-glycoprotein recombinant) has also proved to be effective.

Both live and inactivated vaccines have their advantages and disadvantages (Baer, 1991), but both can be used to immunize animals for periods of between 1 and 3 years (Sihvonen et al., 1994; Basheer et al., 1997; Jenkins, 1998). They are not to be relied on to protect previously unvaccinated animals that have been exposed to infection (Blancou et al., 1991).

In addition to vaccination, prevention of exposure should be encouraged whenever is possible by vaccinating vector animals, and keeping farm animals indoors. A promising widespread oral vaccination technique distributed in baits has been used with promising results in Canada, in the USA and in Europe (World Health Organization, 1989; Krebs et al., 1999; Pastoret and Brochier, 1999).

Control of Vectors

The chemicals warfarin and diphenadione have been used to control vampire bats in South America (Delpietro et al., 1991; Sald and Flores-Crespo, 1991).

Rabies is included on the list of notifiable diseases by the Office International des Epizooties (OIE). Strict quarantine regulation is and should be performed in countries and regions that are currently free from disease. Control of rabies is internationally organized by OIE.

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