Rabies and current concepts in its prevention

Rabies is a zoonotic disease transmitted by bite/lick/scratch of infected animals. It is caused by lyssavirus. Though it is 100% fatal, it is also 100% preventable. It causes 50,000 to 60,000 deaths worldwide and India contributes 17,000 deaths alone. The incubation period is always variable ranging from 3 weeks to 3 months. It manifests in two forms in humans: Furious type (80%) & Paralytic type (20%). Diagnosis of Rabies is mostly clinical as 80% of cases present as hydrophobia, aerophobia and aggressiveness. Demonstration of Negri bodies in brain sample is 100% pathognomonic. Prevention of rabies is by management of animal bite cases. The three pillars of animal bite management are (i) local wound treatment (ii) Passive immunization with RIG in all category-III cases and (iii) Active immunization with modern Tissue Culture Vaccines. Use of PVRV(Sanofi Pasteur) is safe in pregnant women and the WHO has approved the use of PVRV(Sanofi Pasteur) for intra-dermal post and pre- exposure vaccination against rabies.

Rabies is fatal viral encephalitis caused by a single-stranded RNA virus belonging to the genus lyssavirus of the family Rhabdo-viridae. It is a zoonotic disease endemic in India and one of the most dreaded illnesses known to man since ages (1). It is transmitted to humans by the bite/lick/scratch of infected animals. Among human infections rabies is the 10th most common cause of death (2). The term rabies is derived from the Sanskrit word ‘Rabhas’ meaning ‘to do violence’ or Latin word ‘Rebere’ meaning ‘in delirium’. In the year of 1885, 6th July, Louis Pasteur invented the first vaccine and it was administered to a boy named Joseph Meister who was bitten by a rabid dog and ultimately saved.

Rabies causes 50,000 – 60,000 deaths worldwide and it is estimated that every year about 30,000 to 40,000 are from India. The Rabies situation in India has shown some improvement, but the scenario is still not very encouraging. The number of human rabies cases has declined from 30,000 estimated in the 1990s to 17,000 in 2003(4). The WHO-APCRI survey found 28-million pet dog population in India and Annual animal bite incidence to be 17 per 1000 population. Even today, 96% of rabies transmission in India is by dogs, mainly due to irresponsible pet dog ownership practices and widespread stray dog menace.

The virus can be transmitted to man by (a) directly from the bites, scratches and licks over broken skin or intact mucous membrane, by rabid animals, (b) handling saliva of rabid animal or patient, (c) organ transplantation particularly by corneal graft, and (d) ingestion of un-boiled milk of rabid cattle (like cows, buffaloes, goats, camels,etc.)

After local multiplication at the wound site, the virus enters the nerves and travels at the rate of 3mm/hr to the dorsal ganglion. From here, it reaches the anterior horn cells of the spinal cord and brain, developing rabies encephalitis and inevitable death (5).

The incubation period is always variable ranging from 3 weeks to 3 months in more than 85% of cases but it has been reported as early as 4 days to 7 years. The incubation period varies from the site of bite also i.e. in Category III cases, it is much shorter (6).

There is a large animal reservoir. Foxes, raccoons, skunks, mongoose, jackal, monkeys and bats maintain the sylvatic cycle. Dogs, cats, cattle, horses, sheep and pigs maintain the urban cycle.

Rabies manifests in two forms : Furious type (80%) and paralytic type (20%). Hydrophobia occurs only in the furious type of rabies.

The early involvement of hippocampus and amygdaloidal nucleus regions explains the patient’s agitation, hydrophobia, aggressiveness; involvement of hypothalamus explains the sympathetic symptoms, like hypersalivation, irregular temperature and blood pressure.

Diagnosis of rabies is mostly clinical as 80% of cases present as hydrophobia, aerophobia and aggressiveness. Laboratory confirmation is required in atypical and paralytic rabies, which are around 20% of human rabies cases.

Antemortem diagnosis can be attempted by several methods. Most important method is detection of viral antigen in Saliva or CSF. Another important method is corneal smear immunofluorescent examination. The latest method that has been used is the detection of viral nucleic acid in Saliva and CSF by reverse transcriptase (RT)-PCR analysis.

Postmortem diagnosis by demonstration of Negri bodies within the brain sample is 100% pathognomonic of rabies.

Category I : Feeding, touching, petting or licks on unbroken skin.
Category II : Abrasions, scratches without bleeding; licks on broken skin, nibbling on uncovered skin.
Category III : Single/multiple trans-dermal bite or scratch, Mucous membrane exposed to saliva.

If proper wound treatment in animal bite cases is done, the risk of developing rabies reduces by 50-60%. Wound should be washed under running tap water for 15 minutes with soap, preferably a detergent. Water removes the virus mechanically and soap dissolves the lipid envelope of the virus and destroys the virus by detergent action. If soap is not available, simple flushing of the wounds with plenty of water should be done as first-aid.

After cleansing, virucidal agents either alcohol (400-700ml/litre), tincture or 0.01% aqueous solution of iodine or povidone iodine are applied locally. This causes virus inactivation by chemical disruption of glycoprotein coat of rabies virus. Quaternary ammonium compounds (e.g. Savlon, Cetavlon) are no longer recommended.

WHO has recommended use of Rabies Immunoglobulin (RIG) in all category III animal bite cases (3). RIG neutralizes the virus locally. The RIG should be infiltrated in and around the wounds. It is necessary to inject RIG into all wounds. If RIG is insufficient (by volume) as per the dose, it can be diluted with sterile normal saline solution, either equal volume or 3 times, depending on the number of bites and requirement.

Human Rabies Immunoglobulin (HRIG): 20 IU/Kg body weight to a maximum of 1500 IU.

Equine Rabies Immunoglobulin (ERIG): 40 IU/Kg body weight to a maximum of 3000 IU.

ERIG must be administered after a test dose, which is intra-dermal injection of 0.1ml of 1:10 dilution of ERIG in normal saline on the flexor aspect of forearm . Purified equine rabies immunoglobulin has been reported to be safe and affordable alternative to HRIG.

Since 1983, the WHO has indicated its support to limit or abandon completely where economically and technically possible, the production of encephalitogenic brain tissue vaccine and strongly advocates discontinuation of the nerve tissue vaccines.

Administration of a potent tissue culture vaccine with minimum defined potency of more than or equal to 2.5 IU/ IM dose should be done immediately on the anterolateral aspect of the thigh in children and the deltoid region in adults. The gluteal region is not recommended for vaccine administration since apart from the potential of causing sciatic nerve injury, it being an area rich in fatty tissues, might lead to lower and slower levels of neutralizing antibodies.

The efficacy and safety of PVRV(Sanofi Pasteur) used intramuscularly and intradermally have been well established by previous studies and many years of clinical experience.

It has been found by several studies that use of PVRV(Sanofi Pasteur) in pregnancy is safe.

Tissue culture vaccines given in deltoid/anterolateral aspect of thigh by intramuscular route according to the following schedule.

                Day 0            -             1st dose
                Day 7            -             2nd dose
                Day 28          -             3rd dose
                Booster          -            after one year

Rabies is a community health hazard as well as a health-related disaster in our Indian scenario as well as global scenario. While polio is on the verge of eradication, the magnitude of rabies is still underestimated in our country. The goal of eradication of rabies from India has been set by the year 2020.

	Encephalitic Type (80%)	Paralytic Type (20%)
	Hyperactivity hydrophobia/aerophobia	Complete Paralysis
	Paralysis	Coma
	Coma Death (respiratory failure)	Death (respiratory failure)