It is an acute almost invariably fatal disease in man and other warm blooded animals characterized by signs of abnormal behaviour, nervous disturbances such as motor nerve irritability, mania, an attacking complex, inability to swallow, excessive salivation, impairement of consciousness, progressive ascending paralysis and death due to respiratory paralysis.
Etiology
Lyssa virus (Family Rhabdoviridae), RNA virus, bullet shaped virus and neurotropic in nature.
Rabies viruses are highly fragile viruses and susceptible to standard disinfectants.
Sunlight and moderate heat destroy the rabies virus.
There are 25 viruses in this genus, of which closely related rabies viruses are called “Classical rabies viruses”.
The different serotypes of rabies viruses are:
Lagos bat virus
Mokola virus
Duvenhage virus
European bat lyssa virus I (EBL I)
European bat lyssa virus II (EBL II)
Australian bat lyssa virus
Based on antigenicity, rabies virus is classified as fixed or street rabies virus.
Table: Differences between fixed and street rabies virus
Fixed rabies virus
Street rabies virus
The virus is passaged by serial intradermal route in rabbits
It is from naturally occurring infection
Incubation period is fixed and shorter (6-7 days)
Incubation period is variable (11-47 days)
It does not produce Negribodies
It produces Negribodies (Intracytoplasmic inclusion bodies)
No shedding of virus in the saliva
Shedding of virus in the saliva
The virus is not virulent and self-limiting. Used for vaccine production
The virus is virulent and not self-limiting. Pathogenic to warm blooded animals
Primary reservoirs are foxes, bats, raccoons, skunks, dogs, cats and cattle.
Primary reservoirs vary geographically. Wherever the population of non-human primates available, rabies is endemic in those countries.
Rodents and lagomorphs are unlikely to have rabies.
Every year, rabies claims nearly 55000 human deaths, worldwide, most of them being children. Presently the efforts at rabies control have enabled a marginal reduction of rabies deaths from 30000 to 20000 in India annually.
Transmission
The high concentration of rabies virus released from the salivary gland secretions before the onset of clnical signs of rabies
Virus in fresh saliva is transmitted via bite, scratch or abrasion by an rabid animal (rabid dogs shed virus in saliva 5-7 days before showing signs and cat does so for only 3 days before signs)
Contamination of skin wounds by fresh saliva from infected animals
Aerosol transmission has been documented in the laboratory and in caves where bats inhabit (requires a high concentration of suspended viral particles)
Figure 1: Diagrammatic representation of sylvatic and urban cycle of transmission of rabies
Disease in animals
In all animals, rabies is characterized by typical signs of central nervous system disturbance, with minor variations peculiar to carnivores, ruminants, bats and man.
The clinical course, particularly in dogs, can be divided into 3 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.
In any animal, the first sign is a change in behavior, which may be indistinguishable from a gastrointestinal disorder, injury, foreign body in the mouth, poisoning or an infectious disease. Temperature change is not significant and driveling 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. Carnivores, pigs, and occasionally, horses and mules bite other animals or people at the slightest provocation. Cattle bite any moving object. The disease progresses rapidly after the onset of paralysis, and death is virtually certain within 10 days of the first signs. Rabid domestic cats attack suddenly, biting and scratching viciously. Rabid foxes frequently invade yards or even houses, attacking dogs and people. The rabid raccoon is characterized by its loss of fear of man, its frequent aggression and incoordination and its activity during the day, being predominantly a nocturnal animal. In urban areas, they often attack domestic dogs. Bats flying in the daytime are probably rabid.
Furious form (changes in behaviour and stage of excitement)
Tendency to bite either inanimate or animate objects till death
Dog may move to long distance
Shows imaginary catching stance
Dog will attempt to lick water but unable to drink water due to the paralysis of pharyngeal and laryngeal muscles
Drooling of saliva. Photophobia
Changes in barking due to paralysis of vocal cards
Finally, dropped jaw and tongue will protrude and head will drop down
Dump form or paralytic form
Isolated themselves in dark places
Paralysis of lower jaw ("dropped jaw"), tongue, larynx and hindquarters
Not capable to bite
In cats
Furious form is more common
In cattle
Furious form
Violently attack other animals or inanimate objects
Loud bellowing
Incoordination of gait
Excessive salivation
Behavioral changes
Muzzle tremor
Aggression
Sexual excitement
Hyperexcitability
Pharyngeal paralysis
Paralytic form
Knuckling of hind fetlock
Sagging and swaying of hind quarter while walking
Deviation of tail to one side
Drooling of saliva
Yawing movement
Figure 2: Salivation in a calf
In sheep
Hyperexcitability
Salivation
Vocalization
Recumbency
Vigorous wool plucking
Excessive bleating does not occur but continuous bleating is common
Starring of eyes and twitching of lips
In horse
Muscle tremors are frequent and common
Pharyngeal paralysis, ataxia and lethargy
Sudden onset of lameness in one limb followed by recumbency
Violent head tossing
In pigs
Twitching of nose
Excessive salivation
Chronic convulsion.
Rapid chewing movement
May walk backward
Disease in man
There is usually a history of animal bite. Pain appears at the site of the bite, followed by paresthesias. Pain and irritation at the site of bite which is linguiring towards the central nervous system. The skin is quite sensitive to changes of temperature, especially air currents.
The rabies virus travels from the periphara nerves to the brain by following bite by a rabid animal.
The incubation period of the disease is usually a few months in humans (usually 30 to 60 days), depending on the distance of bite, severity of bite, amount of virus inoculated at the site of bite and aggressive status of the rabid animal. Once the rabies virus reaches the central nervous system and symptoms begin to show, the infection is effectively untreatable and usually fatal within days. Death almost invariably results two to ten days after first symptoms.
Attempts at drinking cause extremely painful laryngeal spasm, so that the patient refuses to drink ("hydrophobia" - fear of water). The patient is restless and behaves in a peculiar manner. Muscle spasm, laryngospasm and extreme excitability are present. Convulsions occur. Large amounts of thick tenacious saliva are present. There will be increased lacrimation, frequent micturition and increased percipiration.
The initial symptoms of rabies are often mild fever and pain or paresthesia at the wound site.
As the virus spreads in the central nervous system, progressive encephalitis develops.
Furious rabies is rapidly fatal. Brain stem encephalitis characterized by hydrophobia or aerophobia, phobia towards sound, hyperactivity and fluctuating consciousness. Bizarre behaviour and a lack of focal neurological signs are typical features. Phobic reflexes involve jerky inspiratory spasms that may end in opisthotonos, generalized convulsions and cardiorespiratory arrest. The disease is almost always fatal and without intensive care the patient will die within a few days.
Paralytic rabies runs a less dramatic course, but the final outcome is the same. Flaccid paralysis ascending with pain in the affected muscles and mild sensory disturbances will precede death from respiratory paralysis. However, even in the absence of intensive care, such patients may survive for about a month.
Classification of exposure based involvement of risk
Class I - Slight or negligible risk
Licks on healthy / unbrocken skin
Scratches without oozing of blood
Class II - Definite but moderate risk
Consumption of unboiled milk from suspected animals
Licks on fresh cuts
Scratches with oozing of blood
All bites except on head, neck, face, palm and fingers
Consider rabies as a possible problem in any animal of unknown vaccination history showing central nervous system signs or symptoms.
Fluorescent antibody test (FAT) with corneal impression smear, as well as brain. FAT is highly specific and rapid test (99.9%).
FAT detects different strains using monoclonal antibody. The identifiable strains correlate well with species and geographic distributions observed. This allows identification of source and is an important epidemiologic tool.
Identification of Negribodies (intracytoplasmic inclusion bodies) in the brain impression smear by Seller's staining technique.
Virus isolation from body fluid or brain tissue.
Molecular techniques
For confirmation, a combination of tests should be done
Treatment after exposure
Wound cleaning and immunizations, should be done as soon as possible after suspect contact with an animal and following WHO recommendations, can prevent the onset of rabies in virtually 100% of exposures. Recommended treatment to prevent rabies depends on the category of the contact:
Post-exposure care to prevent rabies includes
Washing and scrubbing the wound with phenolic soap and/or plenty of running tape water
Application of antiseptics
Avoiding bandaging or suturing of wound, or point of contact
Administering anti-rabies immunizations as soon as possible.
Anti-rabies vaccine should be given for category II and III exposures (follow post exposure schedule).
Anti-rabies immunoglobulin, or antibody, should be given for category III contact, or to people with weaker immune systems (up to 50% of human rabies immune globulin is infiltrated around the wound; the rest is administered IM).
Intensive care with attention to the airway, maintenance of oxygenation, and control of seizures in confirmed case of rabies.
Post exposure schedule
If the animal is not previously immunized, post exposure vaccination on 0-day (the day starts within 24 hours after bite), 3rd, 7th, 14th, 28th and if necessary, on 90th day (Essen's schedule).
If the animal is immunized annually 0 day, 3rd and 7th day, put the animal under observation for 10 days. If the animal is died, should follow the full regimen (5 doses).
Zagreb schedule with 2-1-1 regimen on day 0, 7 and 21 is found to be effective
Intradermal schedule
8-site intradermal method (8-0-4-0-1-1)
2-site intradermal method (2-2-2-0-1-1)
In 2005, Jeanna Giese was the first patient treated with the Milwaukee protocol and became the first person ever recorded to survive rabies without receiving successful post-exposure prophylaxis. But, survival rate is about 8% by this protocol.
Prevention of human rabies must be a community effort involving both veterinary and public health services.
Virus is destroyed rapidly at greater than 50°C and survives no more than a few hours at room temperature (but the rabies virus can persist for years in frozen tissues).
Vigorous first aid for bite wounds.
Immediately rush to the health authority if suspected exposure.
Postexposure immunization: Upto 50% of human rabies immune globulin is infiltrated around the wound; the rest is administered IM.
Human Diploid Cell Vaccine (HDCV) is given as 5 injections IM at days 0, 3, 7, 14, and 28.
Vaccination of domestic animals and enforced animal control measures (Animal Birth Control and Anti-rabies vaccination programme: ABC-AR programme).
Controlling stray dog population and proper immunization of household dogs (ABC-AR programme).
Vaccination of high risk personnel.
Awareness prgramme among public.
Vaccination
Pre-exposure schedule
Type of vaccine: Inactivated (from cell culture or embryonated egg vaccine)
Number of doses: Three
Schedule: 0, 7th and 21st or 28th day given by intramuscular or intradermal route (vaccine should not be given at the glutial region)
Booster: After one year then every five years
Contraindication: Severe reaction to previous dose
Adverse reactions: Mild local or systemic reactions; rare neuroparalytic reactions reported
Special precautions: Do not use animal-brain-derived vaccines
In 1885, on July 6th, Louis Pasteur injected the first of 14 daily injections of rabbit spinal cord suspensions containing progressively inactivated rabies virus into a 9-year old boy Joseph Meister, who has been severely bitten by a rabied dog two days before. The immunization was successful. Joseph Meister not only got protection against rabies but also withstood large quantities of virulent virus. Pasteur's immunization procedure was rapidly adopted throughout the world. Hence, every year July 6th is celebrated as world zoonoses day.
