In this article we will discuss about Rabies in Animals:- 1. Definition of Rabies 2. Etiology of Rabies 3. Tenacity of the Virus 4. Animals Susceptible 5. Modes of Infection 6. Pathogenesis 7. Postmortem Lesions 8. Symptoms 9. Course 10. Diagnosis 11. Treatment 12. Protective Inoculation 13. Pre Exposure Immunization 14. Control.
Definition of Rabies:
Rabies is an acute contagious and almost always fatal infective disease or animals characterised in typical cases by symptoms of mental disturbances, increased nervous excitability with subsequent paralysis and death.
Etiology of Rabies:
The causal agent is Rabies virus which is a small (200 x 80 mm) approx. RNA containing bullet shaped virus belonging to the genus Lyssa virus and family Rhabdoviridaei. The virus is neurotropic.
In its most characteristic and purest form, the virus is contained in Central Nervous System of the affected animal. It is also present in salivary glands and their secretion — the saliva, which is infective 3 to 8 days (and according to Pasteur even 10 days) before appearance of any clinical symptom.
The infective material produces characteristic cell inclusions in the nerve cells termed as Negri bodies.
Two epidemiological cycles of rabies are distinguished — Urban and Wild (Sylvatic). Maximum number of animals are infected due to bites of urban rabid animals, specially dogs, which maintain a cycle amongst themselves. The Sylvatic cycle propagates itself within wild animals who sometimes transmit the infection to urban animals. Carnivorous bats have been found to be carriers of rabies and responsible for inflicting rabies to cattle.
Street and Fixed virus:
With the “classic” rabies virus, the distinction should be pointed out between the “Street virus” and the “Fixed virus”.
The “Street virus” as is focussed in natural cases of disease refers to the virus recently isolated from animals and which has not undergone any modification in the laboratory. The strains of the virus are characterised by a very variable incubation period and by their capacity to invade the salivary glands.
The “Fixed virus”, by contrast, refers to strains adapted to laboratory animals by serial intracerebral passages which have a short incubation period of only 4 to 6 days and do not invade the salivary glands. The enhanced virulence being permanent and the maximum obtainable.
Negri bodies:
These are rounded or oral inclusion bodies found in the nerve cells, specially of the brain but are most abundant in the Ammon’s horn of the hippocampus major. They measure from 1 to 15µ or more and contain small, highly refractile, sharply defined bodies.
It may be noted that the longer the incubation period, the better chance have been the Negri bodies to develop; the shorter the incubation period, the less is the chance of development. For this reason, Negri bodies are absent in animals infected with fixed virus.
Staining:
Sections are stained with eosin (McConkey’s modification of Lentz A is best) and then counter-stain with methylene blue 1%. The nerve cells are stained blue with black nucleus and the Negri bodies stained deep red situated within the boundary of the nerve cells. Negri bodies are sometimes found as free bodies outside the nerve cells but these are not usually considered as diagnostic.
However, when the specimen is received in the laboratory and processed as per standard methods which include:
(a) Detection of Negri Body by Sellor’s stain.
(b) Detection of Viral antigen by immunofluorescence — Fluorescent Antibody Test (FAT).
(c) Mouse pathogenicity or Biological test.
Of these tests, the sensitivity of Seller’s staining has been reported to be 75%. It is a rapid and cheap test and the report is available within 2 hours. However, if this test is negative, fluorescent antibody test (FAT) is performed after fixing the smears in acetone for 18 hours in cold.
This is a highly (95-99%) sensitive test but requires sophisticated equipment and trained technologist. The mouse pathogenicity test (Biological test — BT) is the ideal test, yet it does not have much practical utility because the results are available only after 2-3 weeks of observation.
Other tests include, corneal smear examined by fluorescent antibody test. The presence of rabies virus in the saliva can be demonstrated by making a smear and staining with fluorescein conjugated or by inoculating the saliva into experimental animals viz. mice and observing the animal for pathogenicity.
Tenacity of the Virus of Rabies:
Virus contained in the dropped saliva is infective even after 24 hours and when dried as long as 14 hours. At 136° F (58°C), it is destroyed in half an hour. Its destruction by putrefaction is usually slow and in such cases, its virulence has been known to last for even 3 months. The virus is highly resistant against cold, dryness, decay etc. It can remain infectious for weeks in carcasses.
It is inactivated by formaldehyde, sunlight, lipid solvents and various antiseptics. Of chemical agents, 1 in 1,000 Perchloride of mercury, 1% Pot. permanganate, 2% Sulphuric acid, 5% Carbolic or Salicylic acid and 1% Creoline destroy the virus in a few minutes.
Animals Susceptible to Rabies:
All animals and man. Rabies virus can infects all the mammals, may it be a small mouse or a massive elephant. The disease is more frequent in canine species than in other species. Wild carnivora such as jackals may keep the disease going (Sylvatic form) and may infect man and domesticated animals. Other important animals such as skunks, bats, racoons, mongoose and foxes are also capable of transmitting the disease. Cats, monkeys, mongoose, jackals and cattle are responsible for spreading of the disease in India apart from principal source—dog.
In man, the disease is termed as Hydrophobia (or dread of water) due to violent spasms of the gullet making it impossible for patient to drink water, hence the name ‘hydrophobia’.
Modes of Infection of Rabies:
Naturally, through the bites of rabid animals, exceptionally by the virus being conveyed by the saliva to the recent wound or abrasions, by licking or otherwise. The virus cannot penetrate the intact skin but there is possibility of infection through intact mucosa, particularly conjunctiva.
In order to infect, the virus must come in contact with torn nerves, because it has to obtain entrance to nerve tissues and proceed along the nerves to the brain and the central nervous system and cord before any symptoms can appear. It is a neurotropic virus.
Pathogenesis of Rabies:
After reaching the central nervous system, the virus causes damage to the nerve cells and also the vascular wall. Irritation of nerve cells first causes a condition of stimulation manifested by the changes of animal’s general habits, then to reflex excitability and after a time, the degeneration of nerve cells leading to paralysis including paralysis of respiratory muscles which is an immediate cause of death.
At the same time, the virus in the central nervous system spreads along the nerve tract, reaches the salivary glands and soon appears in their secretion.
Postmortem Lesions of Rabies:
Autopsy, even in animals which have died a natural death after a prolonged course of disease, rabies shows nothing very characteristic. In carnivora, specially in dogs, the stomach is somewhat contracted and often empty, or else it contains abnormal and indigestible objects such as straw, hay, pieces of wood, bones, stones, leather, pebbles, feather, hair (even its own) which usually set up an irritation leading to congestion of stomach wall.
Eating of uneatables as mentioned above is done by animals in the furious form of the disease.
Broken teeth, worn and torn foot pads etc. also make one suspect the case to be rabid.
Incubation period — 14 to 60 days in dogs, cats and birds
14 to 80 days in Cattle
21 to 90 days in Horses
21 to 60 days in Swine, Sheep and Goats
9 to 90 days in Rabbits
8 to 60 days in Guinea – pigs
In exceptional cases, the incubation period in any species of animal may be as early as the end of the 1st week or as late as several months, or even 1 to 2 years. Normally, 4 to 6 weeks is the usual average period and depends on proximity and laceration.
Symptoms of Rabies:
The virus must be deposited in the nerve tissues to be carried to the C. N. S. to which all symptoms are referable. All deaths from rabies result from paralysis. Whether paralysis
will be the only phase in rabid animal or it will go through a furious phase of hyperirritability, depends on the amount of virus deposited on the nerve.
The greater the amount of virus and shorter the incubation period, it is more likely that paralytic rabies (so called dumb form) will occur. The less the amount of virus and longer the incubation period, the greater is the possibility that the furious stage will be the predominant symptom.
So, from a clinical standpoint, it is necessary to divide rabies into two types:
(1) Furious rabies and
(2) Dumb rabies.
1. Furious rabies:
In this form, three stages of development are rather sharply defined:
(a) Melancholic stage
(b) Maniacal or Irritative stage and
(c) Paralytic stage.
(a) Melancholic stage:
In this stage, the first thing usually noted is the altered behaviour of the animal. It becomes sullen, afraid, seeks dark places, easily irritated and is restless and obstinate (not obeying its master). It is inclined to hide itself, couching in dark corners or under furniture, makes sudden unusual movements such as snapping or biting at imaginary objects, or barks suddenly without any apparent cause.
The appetite is not much changed in the early stage but later on become capricious, the animal feeling inclined to eat indigestible objects, e.g. wood, wool, leather, feather etc. or even eat its own faeces and laps its urine. A very noticeable symptom is the tendency to grasp objects as if to eat them, then suddenly let them fall from the mouth.
During the latter part of this stage, the animal becomes a bit excitable. It snaps at objects, its master, other persons or animals without provocation. This excitability gradually or very rapidly increases. The nervous reflexes become sensitive and the animal is easily startled by sudden noises, light touch or strong light.
The pupil of the eye dilates and facial expression is changed. The patient often scratches and bites the place of infection, sometimes doing extensive damage to the area. The appetite now is entirely suppressed, but the animal seeks water and attempts to drink but on account of beginning of paralysis of larynx and pharynx, it does not succeed. The salivary, secretion is increased and saliva hangs from the mouth in long strands. This stage usually lasts from 1 to 3 days.
(b) Irritative stage:
In this stage, the symptoms reach a higher degree of development. The excitement increases and hallucinations, which bring about violent fury or rage, are soon apparent. The voice becomes decidedly changed from the normal. This is a very characteristic symptom of rabies and no doubt, results from the congestion and paralysis of the vocal chords.
The animal becomes extremely vicious and if confined, shows a tendency to chew objects and tear them to pieces, and while chewing hard objects, the animal might even break its teeth and lacerate its gums and lips. If a stick is held before the dog, it will attack it viciously but with the peculiarity that it simply bites it instead of holding on to the stick as non-rabid dog usually does.
If the animal is not kept confined, it usually wanders away from home, trotting a long distance comparatively in a short period of time. During this sojourn, the animal attacks and bites other animals and persons that happened to come in its path. The most peculiarity is that while the rabid dog attacks another dog, the latter usually runs away, but if their meeting results in a combat, the rabid dog fights furiously, even in spite of superior strength and size of its opponent, and while the attacked dog growls, the rabid one hardly utters any sound.
If the rabid dog is not killed or incapacitated in any way, it invariably returns to its home greatly emaciated and exhausted, often with marks of injuries resulting from bites of other animals, and in general, with a very much dejected appearance. As this stage progresses, the periods of fury become shorter and soon marked by depression. The voice is still more changed, which becomes a peculiar wail or howl and there is great difficulty in swallowing. This stage usually lasts for 2 to 4 days.
(c) Paralytic stage:
In this stage, the paralysis becomes still more pronounced and the animal becomes less vicious. There is complete loss of voice, the animal is unable to swallow and the mouth is held open with the tongue protruding out, completely paralysed.
The eyes are retracted, they lose their expression and lustre and the pupils are dilated — in some cases unequally and become squint. The general paralysis asserts itself, beginning in most cases at the posterior limbs and rapidly extending to the foreparts and the central nervous system causing death in most cases on the 5th to 8th day of the attack.
2. Dumb rabies:
The clinical picture described under (a) and (b) above, in certain cases is considerably modified, this is particularly in relation to the irritative stage, which is sometimes very short, or even goes unnoticed and is soon succeeded by paralytic symptoms, specially the paralysis of the muscles of the jaw and throat, which is soon followed by that of the hind quarters.
This form of the disease in which there is generally a marked apathy from the very first and the absence of howling and biting, and which is generally fatal in 3 to 4 days is known as dumb rabies, in distinction to furious rabies described earlier.
Rabies in Other animals (Symptoms):
The clinical picture of the rabies is on the whole is same in different species of animals, with certain variations in the symptoms according to mode of life, body structures, temperament of the animals.
(i) Cat:
The furious form is usually noticed. The aggressive stage is most marked and the animal attacking other animal and man with great vigour and injuring its teeth and claws. The course of the disease is usually shorter.
(ii) Cattle:
The animals are affected by the bite of a rabid dog or fox. Dumb form is usually seen. The animal stamps its feet or bellow, salivate from the mouth and break loose and may do much damage. Muscular quivering are seen and there is loss of condition and paralysis sets in. Death occurs in 2 to 6 days.
(iii) Horse:
The furious form is usually noticed. Symptoms include facial twitch, muscular incardination, dull stare a.id biting of wood work. Paralysis of the hind quarters and throat set in and death occurs in 3 or 4 days.
(iv) Sheep, Goat and Swine:
In sheep and goats, symptoms are similar to those in cattle, though excitement is manifested by restlessness, marked sexual desire shown by riding other animals, stamping of the feet but the period of excitement is shorter followed by paralysis and death in 3 to 6 days. In case of swine, it attacks other animals even their own young when excited. They hide in straw, grown at the wound and soon become paralysed.
Course for Rabies:
Not all animals bitten by rabid animals become affected, but if symptoms develop, the disease is invariably fatal within a week. In rare cases, the duration may be 8 days and exceptionally 11 to 13 days. It must be mentioned here that if a dog which bit someone is still alive after 10 days, it cannot be assumed that the dog is not rabid.
Diagnosis of Rabies:
The history of the case, the clinical picture if presents and the unusual postmortem findings are quite diagnostic of the disease. But of course, the presence of Negri bodies detectable by microscope is of outstanding diagnostic importance.
As the definite diagnosis is of great importance, specially in cases where men and animals have been bitten, it is advisable not to kill the suspect but to secure it alive and keep it under close observation for atleast 10 days. If the dog is rabid one, it will almost certainly die within 10 days excepting in very rare cases, it may survive one or two days more.
Although Negri bodies are only found in animals affected with rabies and their presence definitely establishes a diagnosis of rabies, yet they may be absent in the initial stage of the disease and occasionally even later or it may be absent in animals killed soon after the onset of the disease; in such cases, a negative result of microscopic examination does not exclude rabies.
In these cases, the history of the case, the clinical symptoms and postmortem lesions will be helpful in declaring a case as rabies. Moreover, detection of viral antigen by immunofluorescence — fluorescent antibody test (‘FAT) is highly sensitive test (95-99%) and mouse pathogenicity test (Biological test — BT) is the ideal best but the results are available only after 2-3 weeks of observation.
Method of sending brain to laboratory:
Specimens should be placed on wet ice and if possible, delivered directly to laboratory by the messenger. If no messenger is available, the sample should be put in a suitable water-tight metal container and pack cracked ice around it and it must be ensured that the package does not leak, and the sample containing the container, is placed in a large water tight container along with detailed information, e.g. case history, clinical features etc.
Apart from transporting the specimen on ice, the brain tissue can be sent preserved in 50% glycerol saline. In both cases, virus infectivity and the antigen reactive in immune-fluorescence test are preserved. Before making the impression smears, tissues may be washed free of glycerine. Specimens should never be slipped or sent to laboratory in formalin, because formalin makes the specimen unsatisfactory for rabies laboratory testing.
Treatment of Rabies:
No case can possibly be cured once the symptoms develop. However, promising results can be obtained by local treatment of the site of wound with a view to prevent of rabies.
Since rabies virus enters into the body of animal through a bite or scratch, it is imperative to remove as much saliva and thereby the virus, from the wound as is possible by an efficient wound toilet that should not involve additional trauma. This can be done by washing the wound with plenty of soap and water.
If soap is not available, the best course is to flush the wound with copious amount of water. After the removal of soap, any quarter-nary ammonium compound may be applied as the antiseptic along with antirabies serum, if possible. Appropriate wound toilet minimises the risk of rabies greatly by reducing the infective virus load on the injury.
The following points must also be kept in mind:
(a) Do not apply chilly powder, turmeric or oil etc. to the wound.
(b) Cauterisation is no longer recommended as it leaves very bad scars.
(c) The wound must not be stitched at least within 24-48 hours of injury. However, if suturing is unavoidable, first infiltrate the antirabies serum around the wound and then apply the minimum possible stitches.
It is again emphasized that local treatment of wound is extremely important and on its own can prevent many cases of rabies by eliminating or inactivating the inoculated virus. It is strongly recommended that wound must be washed as soon after the bite as is possible.
Protective Inoculation of Rabies:
Animals can be protected against rabies, e.g. inoculation by vaccine both as post-exposure and pre-exposure vaccination. In India, carbolised or inactivated with BPL vaccine is employed for the purpose. The dose suggested for different animals, as fixed up by the authorities of the Pasteur Institute, Kasauli, is mentioned below for post-exposure vaccination:
Pre-Exposure Immunization of Rabies:
A single dose vaccine prepared by different laboratories gives protection against infection for a year. For this purpose, avianised rabies vaccine may be used. The best named one is packed with sterile diluent to make up 2 ml volume for a single subcutaneous or intramuscular injection. Some combined vaccines with canine distemper, hepatitis etc. are also available and these vaccines have been proved to be of great utility. The manufacturer’s instructions supplied with the product should be followed.
Control of Rabies:
In a good rabies control programme, the following must be incorporated:
1. Education of-the community as regards the cause, effects and prevention of the disease.
2. An effective legislation to include:
(a) Licensing of all dogs
(b) Livestock census, specially of dogs to get an idea of dog population
(c) Registration of all pet dogs
(d) Impounding of stray dogs and destruction of unwanted ones
(e) Notification by the owner of suspected or affected dogs
(f) Detention of the suspected
(g) Destruction of the affected animal by humane method
(h) Muzzling while out.
(i) Vaccination of all dogs over 6 months age at least once a year with vaccine of tested potency.