RABIES: TIMELY INTERVENTION CAN BE PROTECTIVE

Rashmi Rekha Kumari 1, Manish Kumar 2 Sanjiv Kumar 1 and Pankaj Kumar3
Bihar Veterinary College
P.O. B V College, Patna-800014

Rabies is an infectious fatal zoonotic disease that causes acute inflammation of the brain in humans and other warm-blooded animals. Rabies is few of the oldest recognized infectious disease affecting animal and humans alike. It has been recognized in India since the Vedic period.Aristotle (384–322 BC) noted the possibility of rabies transmission from an infected animal to a healthy one through a bite.Celsus(25 BC–50 AD) coined the term “hudrophobia”. Avicenna (980–1037 AD)a Persian scholar described rabies in humans and animals and explained its clinical manifestations, route of transmission, and treatment methods.In India rabies is endemic in nature. However, the islands of Lakshadweep, Andaman and Nicobaris reported free from rabies. India has one of the highest numbers of reported cases of human rabies in the world, with undermined estimate of more than 25,000 human cases per year. Reports of rabies in animal of our country is still unexplored and pocketed.In human, 99% death due to rabies are due to bite by rabid domestic or stray dogs and that too more in children. In India, the total number of street dogs in India estimated near about 30 million which are mostly unvaccinated. One finding reports that the annual estimated number of dog bites in India is 17.4 million and estimated animal bites in India/year is 2.28 million. Again it is emphasized that these figures seems undermined as most studies are centred on cities and based on hospital reports.There is no organized system of surveillance of rabies cases and inappropriate to specify actual figures. Once symptoms of the disease develop, rabies is nearly always fatal. However, some protection is possible if timely interventions as discussed below is instituted immediately. Considering these facts it is important to understand the pathogen of rabies, its transmission, symptoms and prevention strategy.


  1. Assistant Professor, BVC, Patna-800014
  2. Assistant Professor, Department of Biosciences and Bioengineering, IIT, Guwahati
  3. Scientist, Veterinary Medicine, DLFM, ICAR Research Complex for Eastern Region, Patna-800014

* email: rrkvet@gmail.com

Etiology

Rabies virus belongs to genus Lyssavirus of Rhabdoviridae and order Mononegavirales, viruses. It is a bullet-shaped, single-stranded, enveloped RNA virus. The virus genome encodes five (N, NS, M, G, L) proteins.
All rhabdoviruses have two major structural components, first one is the ribonucleoprotein core (RNP) and second one is the surrounding envelope. Rabies virus was first isolated by Louis Pasteur and team in the 1880's. Viral multiplication in the salivary gland andit induces aggressive biting behavior in the host animal, thus maximize the chances of viral infection to a new host.
It is very sensitive to some environmental factors and rapidly destroyed by direct sunlight, U.V. irradiation, heat. The rabies virus can be inactivated by soap solutions, ether, chloroform, acetone, 1% sodium hypochlorite, 2% glutaraldehyde, ethanol, iodine preparations, quaternary ammonium compounds or formaldehyde.

Transmission

The rabies virus is maintained mainly in two epidemiological cyclesdepending on whether the principal maintenance host is the domestic dog (urban rabies) or a wild animal species (sylvatic rabies). The sylvatic cycle is the predominant cycle in in Europe and North America. It can also present simultaneously with the urban cycle in some parts of the world. In India Rabies virus usually spread via infected saliva through bite mostly by rabid dog, however reports of sylvatic transmission are available. Other unusual possible routes of infection can be contact with infectious saliva or neurological tissues of infected source through mucous membranes or breaks in the integrity of the skin. Aerosol transmission has been recorded in laboratories and bat caves. Pasteurized milk and cooked meat are considered as safe for human use as the virus is inactivated by heat. However, risk of transmission in unpasteurized rabid cow cannot be ruled out. Organ transplant as cause of transmission from one human being to another is document after cornea transplant. All warm blooded animals including human are susceptible to rabies virus infection. But only a few species are important as reservoirs for rabies virus. In India major species which are suspected as reservoirs of rabies are dog, mongoose, wolves, foxes, coyotes, jackals, cats, bobcats, lions, skunks, badgers, bats and monkeys.Now dog, cat, mongoose, monkey bites can be included in urban cycle of rabies transmission.
Route of infection after transmission:
Immediately after infection, the rabies virus enters an eclipse phase and it replicates in non-nervous tissue such as muscle. After several days or months, the virus spreads to the nerves by binding to the Acetylcholine (Ach) receptors or other neurotransmitter receptors. Movement of the virus up the axons of the peripheral nerves eventually leads the virus to the Central Nervous System (CNS). After dissemination within the CNS, where clinical signs develop as the neurons are infected, the virus is distributed to highly innervated tissues via the peripheral nerves. Most of the virus is found in nervous tissue, salivary glands, saliva and cerebrospinal fluid. Blood, urine and faeces are not thought to be infectious.

Symptoms in Dog

The incubation period is prolonged and variable depending upon the site of bite and nature of bite. Delay in pathogenesis is due to eclipse phase of the virus after inoculation. This eclipse phase provide opportunity for effective action of local infiltration of rabies immune globulin during postexposure prophylaxis. Most rabies cases in dogs develop within 3 to 11 weekspost exposure.
            Rabid dogs usually exhibit signs of central nervous system disturbance, with some variations among species. Noteworthy signs are abruptbehavioural changes and progressive paralysis. Appreciable behavioural changes are appreciable such asanorexia, signs of anxiety,apprehension, irritability and hyperexcitability. The animal tries to seek loneliness. Ataxia, altered phonation may be overt. The clinical manifestation in dog may be divided into three phases i.e. prodromal, furious and paralytic. The prodromal period maylastfor 1–3 days andaffected dog show only subtle signs. The furious form is the mad-dog syndrome. The animal becomes irritable and may bite even moving object upon slightest provocation and even noise. The expression is alert with anxiety anddilated pupils. Affected dog lose control and fear of people and other animals. They commonly swallow foreign objects. Rabid domestic cats, similar to rabid dog cansuddenly biteor scratch violently. The disease pathogeneses progresses withsymptoms of muscular incoordination and seizures. Death results from progressive paralysis.
Paralytic (dumb) form is manifested by ataxia and paralysis of the throat and masseter muscles. Itis common to observe profuse salivation and inability to swallowand dropping of lower jaw in the dumb form. Pet owners/animal handlersmay examine the mouth of affected dogs or attempt to administer medication without any protection with their hands, exposing themselves to the virus.Often these animals are not violent nor attempts to bite. The paralysis generalizes rapidly to all parts of the body. Coma and death are likely events within few hours.

Symptoms in Human:

In human five general stages of rabies are recognized. It includes incubation (5 days to > 2 years), prodrome (0-10 days), acute neurologic period (2-7 days), coma (5-14 days), and death. The early symptoms may include nonspecific prodromal signs such as malaise, fever, headache, pain, pruritus at the site of bite. After several days, anxiety, confusion and agitation may appear, and progress to sleeplessness, abnormal behaviour, hypersensitivity to stimulus, disorientation, illusions, slight or partial paralysis, hyper-salivation, difficulty swallowing, and convulsions. Either an encephalitic (furious) form with hyperexcitability, autonomic dysfunction and hydrophobia, or a paralytic (dumb) form characterized by generalized paralysis, may predominate. Death usually occurs within 2 to 10 days.

Diagnosis:

            Diagnosis in affected dog in furious form is very easy to recognise, however dumb or paralytic form is difficult to suspect based on clinical manifestations. In veterinary practice, diagnose of rabies is made after detection of rabies virus from any part of the affected brain, preferably the brain stem and cerebellum by fluorescent antibody test (FAT).Direct FAT is considered as "gold standard" diagnostic method.Histopathological test is based on detection of intracellular Negri bodies in the pyramidal cells of Ammon's horn and the Purkinje cells of the cerebellum using Mann's, Giemsa or Sellers stains. The presence of Negri bodies is variable and is neither as sensitive nor as specific compared to other tests.Immunohistochemistry methods in formalin-fixed tissues for rabies detection provide sensitive and specific means for diagnosis.

Treatment and Control:

            Post-exposure prophylaxis consists of immediate wound cleansing and disinfection, followed by rabies vaccination and the administration of human rabies immunoglobulin. WHO indication for post-exposure vaccination with or without rabies immune globulin depends on the type of contact with the rabid animal. Types of contact includes category I (touching or feeding animals, licks on the skin); category II (chewing of bare skin, minor scratches, abrasions without bleeding, licks on insulted skin); category III (single or multiple trans-dermal bites or scratches, infection of mucous membrane with infected saliva). Treatment is not required for cases classified under category I. Bites or cases of category II requires immediate vaccination and for category III immediate vaccination along with administration of rabies immune globulin are recommended by WHO. The rabies vaccine with inactivated cell culture rabies virus with potency > 2.5 IU (Rabipur®) is given as 5 doses (0, 3, 7, 14 and 30 day) and it is usually administered intramuscularly (1ml or 0.5 ml depending on type of vaccine) in the arm of affected human. Post-exposure prophylaxis is highly effective if immediately used after exposure.Two intramuscular doses of a cell-derived vaccine separated by three days are recommended for individuals who are previously exposed to the virus and have received either pre or post exposure vaccination. Use of immunoglobulin either homologous or heterologous has been reported to be useful in decreasing fatality. Recommended doses for human homologous anti-rabies immunoglobulin is single dose of 20 IU per kg of body weight and 40 IU per kg of body weight for heterologous immunoglobulin.The first dose of vaccine should be inoculated at the same time as the immunoglobulin but at different site of the body.
Similar doses of post bite vaccine is recommended for suspected dog bite in animals. In case of bite to a domestic animals similar 5 doses of post bite vaccine is recommended using inactivated tissue culture vaccine with potency > 1 IU such as Raksharab®, Rabigen® rationalising on cost of treatment.Use of immunoglobulin is not in practice in animals due to high cost involved. Asymptomatic dogs, cats or ferrets that have bitten humans are observed for 10 days. If the animal develops symptoms of rabies during this time, it should be euthanized and tested for rabies.

Prevention:

Prevention is possible by being smart citizen of India and follow the following as per the requirement and situation:

  • Pet dogs and cats should be vaccinated with anti-rabies vaccine to prevent them from becoming infected.
  • Stray animals should also be controlled. Programs like animal birth control (ABC) and vaccination is effective in controlling stray dog population and rabies.
  • Cats are readily infected by rabies, but a cat-specific variant does not occur in feline populations.
  • In pet dog first anti-rabies vaccine should be given at 3-4 months of age, followed by booster doses every year.
  • All person including veterinarians, animal handlers who are at high risk for acquiring infection from animals should also receive prophylactic anti rabies vaccine.
  • Pre-exposure rabies vaccination for human consists of three full intramuscular doses of inactivated vaccine having potency > 2.5 IU and given on days 0, 7 and 21 or 28.
  • Recommended sites for pre-exposure vaccine in adult is the deltoid area of the arm and the anterolateral area of the thigh for young children less than 1 years of age.
  • Veterinarians and animal handlers should handle potentially rabid animals with extreme caution. Protective clothing such as thick rubber gloves, eye goggles and a plastic or rubber apron should be worn when doing autopsies or in other circumstances when exposure to infectious tissues could occur.
  • Preventing animals from roaming will reduce the risk of exposure to rabid wild animals.

Strategy Required for Controlling Rabies:

  1. Strict legislation for licensing and vaccination of pet dogs
  2. Quantification of virus burden in Domestic and stray dog population
  3. Implementation of control program such as ABC for control of stray dog population
  4. Enforcement and dissemination of awareness about rabies prevention through existing extension system.
  5. Print and press media public awareness at frequent interval
  6. Government attempts free availability of post bite anti-rabies vaccine and immunoglobulin
  7. Promote NGOs involved in controlling stray dog population

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