Synonyms: Hydrophobia,Lyssa,Tollwat,le rage

This is an acute viral infection in man and other warm blooded animals characterized by signs of abnormal behaviour, nervous disturbances such as increased excitability and irritability, impairment of consciousness, ascending paralysis and death.

Etiology

R.N.A. virus, Family Rhabdoviridae, Genus Lyssa virus. The virus is bullet shaped in structure and measures about 180-250 nm in length by 75 om in diameter (Murphy, 1975).

The virus again has been grouped into street virus and fixed virus. The street virus is derived from one that exists in nature in naturally occurring cases and the fixed virus denotes to strains of virus that has been adapted by serial intracranial passage in some animal (rabbit) in the laboratory. And this is used in vaccine production. Fixed virus causes paralytic disease with.a relatively short Incubation period following intracerebral inoculation, absence of negri bodies and absence of virus in salivary glands and saliva.

Resistance to physical and chemical action

The virus is heat susceptible and very much sensitive to ether, chloroform, formalin and other detergents e.g. Potassium permanganate, phenol, alkali, bichloride, of mercury, sunlight and moderate heat destroy the virus. The virus can be preserved in 50% glycerol and it can survive in tissue culture at 37°C for a week.

Susceptible hosts

All warm cular animals are susceptible and there is no difference in, susceptibility with relation to age of the animals. The susceptibility varies in different species. Animals like dog, fox, wolf, jackal, skunk, mongoose, cat, rat, squirrels, vampire bat are extremely susceptible in the tropical areas of the world. Cattle, goat and sheep are moderately susceptible. Cattle and Equidae may be considered as dead end hosts for rabies virus. In that, the disease is usually not transmitted directly to other species.

Distribution

The disease is known since ancient times. The disease has been recorded in various parts of the world in different species of animals (W.H.O., 1979). In India, there is report of the disease in 5000 years ago in vedic period. In 500 B.c. Democritus ascribed the disease in animals. Aristotal 300 B.c. drew attention to the danger of biting of rabid dog. The disease is noted in most of the tropical countries of the world. Australia, Newzealand, Papua, New Gunea, Pizi, Bahamas, Turks, Hong Kong, Singapore, Brunei, Baharin, Cyprus, Britain, Howei are the countries presently free from rabies. Japan is the first in Asia to eradicate rabies.

Mode of transmission

• Bite of rabid animals, usually carnivorous animals.
• Aerosol infection is possible.
• Aberrent route such as ingestion and inhalation may play a significant role in the natural spread of rabies

The virus is excreted in the saliva 3-8 days prior to manifestation of clinical symptoms

The infective virus travels centrifugally from peripheral nerves to the spinal cord and the brain. It then travels centripetally to the salivary glands. The virus in no case enter the salivary glands prior to being in the brain

The ability of the virus to reach the central nervous system depends on various factors. They are as follows:

• Age of the animal – Younger animals are considered more susceptible over adults.
• Site of bite – The distance of the bite from the central nervous system is an important factor in the virus reaching the brain. In man, the virus can reach the brain from facial wound in 30 days, from the arm in 40 days and from the legs in 60 days.
• Virulence of the virus – More the virulence, more the chance of clinical disease.
• Concentration of the virus
• The degree of wound. The presence of hyaluronidase in the saliva has got disease inducing effect. Ths saliva of wild carnivores has a high hyaluronidase content which is found to be increased at the time of attack. This increases the permeability of tissues and accelerates the virulence of the virus. In the initial phase of rabies, saliva should be considered infective

Pathogenesis

Following bite, the virus is deposited in the wound by the infective saliva. Then there is local replication of the virus in the epithelial cells or myocytes The virus then cross the neuromuscular and neurotendinal spindles and move centripetally to the central nervous system via nervous pathways as the infection progresses Ancillary or alternate pathway for spread of virus via blood or lymph in severe bite has been suggested. It has been suggested that virus may replicate in muscle fiber before invading the nervous system and this replication of virus in muscle cells may indicate an amplification step to produce huge quantities of virus to invade the peripheral nervous system After reaching the brain, virus invade ganglion cells and spread centrifugally to the peripheral nerves (facial, glossopharyngeal, trigeminal, olfactory) from the brain. Virus may reach salivary glands, thymus, lymph nodes, taste buds, olfactory cells and then oral and nasal secretions The salivary glands show degenerative changes of the acinar epithelial cells along with infiltration of plasmocytes and lymphocytes The electron microscopy shows presence of virus in the cornea which might have reached through peripheral nerves The virus may be excreted through milk of cow but infection through milk has not been the rule. The virus cannot be demonstrated in the blood. The virus may invade the foetus through infected pregnant bitch.

On invading the brain, virus damage the brain stem and medulla. Irritation of nerve cells causes increased excitability. Infected nerve cells undergo degeneration and there is paralysis of various muscles. Due to paralysis of the muscles of deglutition, the animal is unable to swallow. There is drooling of saliva. Paralysis of jaw muscles prevent closing of jaws as such there is dropped jaw. Paralysis of respiratory muscles cause asphyxia and death.

Mild pulmonary atelactasis and tracheal and bronchial congestion are the features in rabies in cattle. These lesions may be responsible for bellowing which is an important clinical attribute.

Clinical findings

Clinical manifestation in dogs

Two types of syndromes are noted in dogs. They are considered as furious form and dumb form. But, this distinction is not always possible.

Furious form.

It refers to syndrome in that excitation is the predominant changes and it can be divided into stages of melancholy and stage of excitation.

Stage of melancholy.

Here, there is change in the behaviour of the animal. The dog may show the tendency to bite either inanimate or animate objects. It often does not obey its master. It may show unusual violence and frenzied behaviour. Dogs those are under restraint bite nearby objects e.g. door, wire, cage, feeding vessels etc Infected dog remains unusual ly alert. They may respond very sharply to any stimulus. There is strabismus. Dogs will snap or bite imaginary objects. They may show imaginary fly catching stance. There is no deviation in appetite in the initial phase, but later it becomes depraved. They will have the urge to chew or bite or eat non-edible substances e.g. stone, bone, mud, straw, grass or even their own faeces. Dogs show intense irritative signs towards unknown strange person or animal. Gradually signs of excitability increases. The pupils get dilated and there is altered facial expression. Appetite is entirely suppressed but the animal may lick water and attempt to drink water but due to obvious paralysis of pharyngeal and laryngeal muscles does not succeed to drink water.

Saliva hangs from mouth in long strands. The above period lasts for 1-3 days

Stage of excitement.

In this stage, the excitability and irritability increases and dogs become very much aggressive, This period may last for 1-7 days. At the onset dog may hide in dark place due to photophobia. Later on, the animal will develop urge to bite It will experience less sense towards pain when bitten by other animals. During violent attempt of chasing, the dog may break the teeth, injure the gum and head. There is visible change in the sound of barking, which is very characteristic. The animal is unable to swallow. There is drooling of saliva. The change of voice may be pointed out as a deciding factor to differentiate it from normal voice. This is due to paralysis of the vocal cord. After some time the infected animals will show signs of emaciation, exhaustion and dejection. There will be incordination and muscle tremors. Animals may lick their genitalia. The bitch may show the signs of heat and accept the male. In the fag end, the dog will lose its ability to bark ; the lower jaw will hang, tongue will protrude and head will drop down. The dog will develop dyspnoea, ascending paralysis, coma, and death. The total episode may last as long as 10 days

Dumb form.

This form is also known as paralytic form. In this form, there is paralysis of the lower jaw, tongue, larynx and hind quarters. The dogs are not capable to bite but their saliva remain infective, throat muscles are paralysed. There is hanging of the jaw due to paralysis of jaw muscles. The dog is unable to close the mouth (open mouth condition). In fair percentage of cases, the owner is suspicious that a bone or some other object might have stuck in the throat and the owner may try to open the mouth for examination and thus predispose them to the possibility of contracting the infection. This aspect should be viewed with utmost care by the owner and the veterinary clinician. In the terminal stage of the disease dogs show progressive weakness and paralysis which cause them to stagger or fall. Ultimately there is coma and death. The entire clinical course of the disease upto death takes 1-7 days

Clinical findings in Cat

The rabies in cat is usually more furious in form than dog.

Clinical findings in Cattle­

Cattle and buffalo show signs of incoordination. There is loss of appetite and sudden fall in milk yield. There is trembling and twitching of ears. There is paralysis of the muscles of deglutition with excessive salivation and grinding of teeth. They tend to slobber and have difficulty in drinking of water. They often show signs simulating choke. Cattle will bellow incessantly in a characteristic low pitched voice due to vocal cord paralysis. Increased sexual excitement may be noted both in, cow and bull. In field cases, bellowing and excessive salivation are the most common signs

Clinical findings in Sheep

Clinical signs are more or less similar to cattle and buffalo. Remarkable symptom is sexual excitement. Animal shows restlessness, staring eyes, twitching of lips, salivation, and aggressiveness

Clinical findings in Goat

Goat shows more aggression and continuous bleating.

Clinical findings in Pig

Pig may become furious and attempt to bite any accessible objects

Classification of exposures

Class I :

Slight or negligible exposure, i.e. minimum risk. All cases of licks (except those on fresh cuts and scratches drawing blood ).

Class_II

Moderate exposure, i.e. definite but moderate risk.

1. All bites except those on the head, neck, face, palm and finger, and less than five minor wounds in number.
2. Licks on fresh cuts and scratches drawing blood.

Class III

Severe exposure, i.e. definite and grave risk. All bites on the neck or above, palm and finger. Lacerated wound/wounds anywhere on the body, multiple bites (5 or more wounds), wolf, jackal and other wild animal bite.

Diagnosis

• Detection of Negri bodies – in the Gasserian ganglion, hippocampus, medulla oblongata or cerebellum.Negri bodies determination is indicative of rabies but negative results cannot exclude rabies.
• Mouse inoculation test.
• Corneal test or saliva test. This is based on the demonstration of rabies virus antigen in the corneal epithelium and the saliva of the patient. This is the only test that can be done prior to death.
• Fluorescent antibody technique (FAT).
• Immunoperoxidase test (IP).
• Complement fixation test.
• Rapid rabies immunoenzymatic diagnosis (RRIED)
• DOT-hybridization test.
• RT-PCR. One tube reverse transcription polymerase chain reaction (RT-PCR) can be used as practical application as confirmatory test to fluorescence antibody. (FAT) or mouse inoculation (MIT) in busy rabies diagnostic laboratories

Preservation of brain and salivary glands

If the brain and salivary glands are to be sent through messenger, they should be carefully packed in polythene bags and placed inside a wide mouth thermoflask containing ice. But, if they are to be sent through mail following steps are recommended

1. Divide the brain into two equal halves with a brain knife by cutting vertically through longitudinal sulcus.
2. Place a layer of cotton about 1 cm thick at the bottom of a wide mouthed leak proof glass or polythene bottle.
3. Put one half of the brain inside the bottle.
4. Add methylated spirit or formol saline, 10 times the volume of the brain.
5. In another wide mouthed bottle, place the other half of the brain and add 50% glycerol saline 10 times the volume of the brain.
6. In third bottle preserve both salivary glands in 50% glycerol saline.
7. Close the lids of the bottles firmly. Security against leakage should be ensured by dipping the mouth of the capped container upto the neck in melted paraffin.