B058 - RABIES

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B058 - RABIES

Nature of the disease
Rabies is a fatal zoonosis caused by Lyssaviruses of the Rhabdoviridae family. Part from the classical rabies virus, there are 6 other lineage of viruses of the Lyssavirus genus responsible for rabies-like diseases, these are: Lagos bat virus, Mokola virus, Duvenhage virus, European bat viruses and Australian bat virus.

It can affect all warm-blooded animals and causes neurological disorders. It is characterised by a almost unique method of transmission (the bite of a rabid animal) and a long incubation period.

Classification
OIE List B disease, biosafety level 2 (except 'street strain' which is level 3)
Susceptible species
All warm blooded animals — including humans — are susceptible.

Susceptibility varies. The less susceptible specie is opossum. Many species can be considered ‘dead end’ hosts while others play an important role in maintaining the disease. In any given area the rabies virus appears to adapt to a specific host species which then tends to maintain the disease. Specific rabies biotypes can be identified by monoclonal antibody studies.

The important animal groups for maintaining rabies are:

  • Canidae — dogs, foxes, jackals, wolves, etc.
  • Mustelidae — skunks, martens, weasels, etc.
  • Viverridae — mongooses and meerkats
  • Procyonidae — raccoons
  • Chiroptera — bats
Distribution
Rabies is present in most of Europe, throughout Africa, the Middle East, most of Asia, and the Americas. United Kingdom, Ireland, parts of Scandinavia, Japan, Singapore, Australia, New Zealand, Papua New Guinea and the Pacific Islands are free. 

Recently, a rabies-like disease due to a previously unknown Lyssavirus has been found in bats in Australia.

Clinical signs 
Clinical signs can be very variable and potentially rabid animals should be approached with extreme caution. In all species the incubation period varies considerably from two weeks to several months, and death occurs 2 to 10 days after the onset of symptoms, rarely after 2 weeks. Recovery is exceptional.

Usually the clinical signs change during the illness, different forms of the disease are described that may differ between species but abnormal behaviour is a constant.

Dogs

In dogs there is a prodromal stage lasting 2-3 days which is characterised by a sudden change in temperament. This is followed by ‘furious rabies’, ‘dumb rabies’ or a combination of both. 

The furious form includes:

  • Unusual agitation, with hypersensitivity to sounds and movements,
  • A puzzled and anxious face,
  • Aggressions towards inanimate objects or other animals with biting and snapping,
  • Dilatation of pupils and loss of corneal reflex,
  • Variable appetite with sometimes apparent inability to swallow, sometimes swallowing of foreign objects,
  • Extensive roaming,
  • Change in voice, with low-pitched, hoarse howling,
  • After 1-4 days rapidly progressing ataxia, convulsions and ascending paralysis.

The dumb form includes:

  • Lethargy,
  • Muscle tremors,
  • Early paralysis of the throat (jaw, tongue, larynx) causing salivation and inability to swallow,
  • Paralysis of hindquarters,
  • Rare bites, usually only when provoked,
  • Coma and death within a few days

Cats

  • Clinical signs similar to dogs but furious form occurs in about 75% of cases,
  • During the prodromal stage, uneasy facial expressions, frequent mew and restless movement of the front feet,
  • Cats tend to be more aggressive than dogs,
  • Muscular incoordination and seizures are common.

Horses

  • Lameness, ataxia and recumbency are early distinctive signs,
  • Periods of marked excitement and aggressiveness alternate with periods of distress and calm,
  • Salivation, 
  • Sexual excitement,
  • Signs of acute colic,
  • Biting,
  • Self-mutilation,
  • Aimless wandering, staggering and progressive paralysis.

Cattle

  • Initial depression and cessation of milk production,
  • Paralysis of throat muscles, grinding of teeth and excess salivation,
  • Low pitched bellowing,
  • Sexual excitement in bulls,
  • Furious signs with attack over other animals, 
  • Paralysis, coma and death.

Sheep

  • Very similar to cattle,
  • Aggressive butting of other sheep and objects,
  • Anorexy,
  • Sexual excitement in rams,
  • Excitation phase followed by depression, weakness, paralysis, recumbency and death.

Pigs

  • Trembling and withdrawn,
  • Attack and bite if provoked,
  • Abnormal grunting,
  • Anorexy,
  • Alternating periods of intense activity and recumbency,
  • Clonic convulsion,
  • Progressive incoordination, paralysis and death.
Post-mortem findings 
There are no characteristic gross lesions. Stomach may contain abnormal objects (sticks, stones etc).
Microscopic lesions are found in the central nervous system (Negri bodies).
Differential diagnosis 
  • Canine distemper and infectious canine hepatitis,
  • Aujeszky's disease
  • Borna disease,
  • Equine viral encephalomyelitis
  • Equine encephalosis
  • Bacterial and mycotic diseases of the central nervous system including listeriosis and
    cryptococcosis
  • Poisons — including '1080' (sodium fluoroacetate), heavy metals (such as lead), chlorinated hydrocarbon and organophosphate pesticides, and nitrogen trichloride
  • Foreign bodies in the oropharynx or oesophagus and other traumatic injuries
  • Acute psychosis in dogs and cat
  • Teschen's disease
  • Erysipela
Specimens required for diagnosis 
Diagnosis can be based on identification of the agent or on serological tests.

Serological tests include Virus Neutralisation, Rapid Fluorescent Focus Inhibition Test (RFFIT) and ELISA but as the seroconversion occurs lately these tests are more often used to assess the vaccination level.

For the identification of the agent many techniques are available, based on processing brain samples.

As collecting such samples can be hazardous and that they are easily spoiled it should be done only by skilled technicians. 

It is possible to send the all head of the animal or alternatively to collect samples from foramen or retro-orbital route using a pipette. 

Shipment of samples must fulfill international standards and insure that no leaking is possible. Heads should be wrapped with absorbent material, placed in a leak proof container and sealed in plastic bag within insulated boxes containing refrigerant. 

If those conditions cannot be fulfilled OIE recommend to submit preserved samples 

  • either in a solution of 50% glycerol in phosphate buffered saline (BPS) which allows to perform Direct Fluorescence Antibody test, Immunohistochemistry, histology or isolation,
  • or in formalin but then the virus is inactivated and isolation is no longer possible.
Transmission   
Rabid animals start excreting the virus up to 5 weeks before the onset of clinical symptoms, so there is potential for the disease to spread from apparent normal animals. 

Two rabies cycle are recognised depending on whether the principal maintenance host is the domestic dog (urban rabies) or a wild animal species (sylvatic rabies).

Rabies is transmitted by contamination of a fresh wound with infected saliva. This is usually from the bite of a rabid animal, but can also result from licking abraded skin or mucous membranes.

Respiratory transmission can occur, it seems to be important in the contamination of people by bats as the virus could be in aerosol in the caves, due to the excretion of infective saliva by bats emitting their high-pitched sounds. 

Oral transmission by ingestion also occurs and is used in the oral vaccination of wild animals.

Transplacental and seminal transmission have been shown. 

Risk of introduction   
The highest threat for rabies introduction is through the illegal entry of an infected animal e.g. through smuggling, fishing vessels or itinerant yachts. 

As dogs are the most likely risk species to be introduced, a dog biotype virus is the most likely type to be introduced. Should such an animal bite other dogs, an urban rabies cycle could be established.
Introduction of sylvatic rabies through illegal entry of wildlife while possible is less likely.

Humans cases from people exposed overseas may sporadically occur but as humans are dead end hosts there is no risk that they will spread the disease.

Spread of Australian bat viruses to Papua New Guinea by movement of bats should be considered as the range of one of the virus carrier, the black flying fox (P. alecto), extends to the north of Australia into Papua New Guinea and the eastern islands of Indonesia. 

Control / vaccines  
There is no treatment for rabies.

Prevention is done through vaccines. First vaccine against rabies was prepared by Pasteur in 1885. Now all kind of vaccines are available:

  • Killed or inactivated vaccines are the safest vaccines and should be used in rabies free countries, however they require the use of an adjuvant, yearly booster and they do not protect against other Lyssaviruses.
  • Live vaccines are very effective through the oral route and they are used to control rabies in wildlife, successful campaign were carried in Switzerland, France and Canada.
  • Live recombinant vaccines are also effective and are to be used in the control of rabies in wildlife.

Protection of Humans at risk (e.g. veterinarians, animal handlers) is insured by vaccination using inactivated vaccines.

Urban rabies can be effectively controlled by registration and compulsory mass vaccination of owned dogs and elimination of stray dogs and cats. Vaccination of livestock is not essential for eradication, but may be desirable to reduce sporadic cases in these animals.

Where sylvatic rabies occurs, contact between dogs, cats and wildlife should be reduced as much as possible. Oral vaccination of wildlife using bait systems has proven effective in the control and elimination of wildlife rabies in Europe and Canada.

References
  • KING AA (1998) RABIES In Zoonoses, ed by SR PALMER, Lord SOULSEY and D.I.H. SIMPSON, Oxford University Press, Bath Press, Avon, 1998, p.437-458
  • Office International des Epizooties, 2002
  • Rabies, In Merck Veterinary Manual, National Publishing Inc. Eight ed, 1998, Philadelphia, p 966-970
  • Rabies, In Veterinary Medicine, Saunders, Eight ed, 1997, London p. 1087-1094