Rabies (hydrophobia) is an acute viral disease characterized by inflammation of the central nervous system with fatal results. It is primarily a disease of animals and all warm blooded are susceptible to the infection.
The main sources of infection in man are dogs, monkeys, cats and wild animals. The Rabies (hydrophobia) disease is transmitted either by the bite or licking of the freshly abraded surface of the skin by an infected animal.
Rabies virus is a neurotropic one which has special affinity for attacking the grey matter of the nervous system. It is a small bullet shaped, enveloped single stranded RNA virus, approximately 200 x 80 nm in diameter belonging to the family RHABDOVIRIDAE.
The glycoproteins bind it to acetyl choline receptors and thus contribute to its neuro-virulence. The virus is highly resistant to cold, dryness and decay but is inactivated by Sunlight, formaldehyde, lipid solvents and antiseptics.
Rabies occurs world wide and its incidence is approximately 30,000 cases per year. The disease is especially common in South East Asia, Africa, Philippines and Indian subcontinent though the incidence is less in countries like Australia, America, Great Britain, Scandinavian countries and Japan.
In India, rabies produces great morbidily and mortality. It is estimated that more than 25,000 persons die of hydrophobia. Every year in India approximately 5,00,000 persons undergo rabies immunization. Dogs remain important vector of rabies virus for humans.
There are two epidemiological forms of rabies.
1. Urban which is primarily propagated by UN-imminised domestic or street dogs and cats.
2. Sylvatic (wild). This form is propagated by foxes, skunks, monkey’s jackals, wolves, mongooses, raccoons and vampire bats. Spillover from sylvatic reservoirs of infection results in infection of domestic animals and man can be infected from both these sources.
Bite by an infected dog and scratch wounds of the skin allow the virus in the saliva access to the tissues. Human to human transmission is not common though, transplantation of infected tissues like cornea may result in rabies in the recipient.
After entering the human body, the live virus replicates within the striated muscle cells and neuro muscular and or neuroendothelial spindles. It penetrates the nerve endings and via peripheral nerves, spreads to the central nervous system where it again proliferates before invading the salivary glands, lungs, kidneys, heart, adrenals and other organs via peripheral nerves.
The incubation period of rabies is variable ranging from 10 days to over 1 year. It is shorter in case the bite site is closer to the brain. Occasionally the incubation period may be as late as 2-5 years.
The time period depends on viral load, distance it has to travel from the site of inoculation to the central nervous system, and hosts immune responses. Histo-pathologically, the white and grey matter of the brain show severe degree of congestion, perivascular and perineuronal infiltration with lymphocytes and plasma cells.
Intracytoplasmic inclusion bodies (Negri bodies) are characteristic of rabies. Negri body is an eosinophilic mass of fibrillar matrix and virus particles about 10 nm is size are present in 80 percent of cases.
Negri bodies are seen in large numbers in the cerebral cortex, the brain stem, purkinje cells of the cerebellum, Pyramidal tracts, basal ganglia and spinal cord. Absence of negri bodies does not rule out the diagnosis of rabies.
These are primarily divided into three phases:
(a) Prodromal phase
(b) Acute encephalitic phase
(c) Paralytic phase and rarely recovery phase.
It lasts for up to 4 days and is characterized by fever, malaise, headache, increased fatiguability, restlessness insomnia, anorexia, nausea and vomiting. There is often complaint of parasthesias and tingling sensation round about the site of bite.
Acute encephalitic phase
It comes about 10 days after the prodromal phase and is characterized by marked restlessness, anxiety and agitation as well as hallucinations, bizarre behavior and sudden spasmodic spasm of the mouth, larynx and respiratory muscles. A typical attack maybe induced by offering the patient water.
Once the spastic form sets in, sensory stimuli which may be tactile, auditory or photic provoke an attack. The synaptic resistance in the reflex arc becomes so lowered that a variety of sensory stimuli such as sudden noise, cold air, bright light, strange smell and even the suggestion of water may induce an attack.
Body temperature rises, frothy saliva collects in the throat and mouth. Disturbances of autonomic nervous system like increased lacrimation, salivation, postural hypo tension and excessive perspiration are present.
Involvement of pyramidal tracts results in increased deep tendon reflexes and plantar response. Paralysis of the vocal cord occurs. This phase where swallowing of liquid and later on a spray of water or its site produces distressing symptoms like oropharyngeal spasm and respiratory distress is called Hydrophobia and is diagnostic of the condition.
This phase lasts not more than 4-5 days and sometimes death may occur due to respiratory paralysis.
Paralytic phase (DUMB Rabies)
If patient survives long, there is development of various forms of paralysis like ascending paralysis (Guillain Barre type), paraplegia, Hemiplegia. Patient lies exhausted and may die in coma. This type of rabies is commonly seen after bites by rabid bats.
Rabies in the dog
Earliest sign is change in behavior followed by irritation, vicious fury and animal runs like a mad dog biting anybody coming in its path. As disease develops, there is change in the bark, swallowing becomes difficult, jaw drops and paralysis develops. This period lasts for 2 to 4 days after appearing of first symptoms and is followed by death.
Laboratory investigations – Specific diagnosis of rabies depends on
(1) Isolation of virus from infected secretions (Saliva, cerebrospinal fluid)
(2) Fluorescent antibody (FA) staining for viral antigen and
(3) Histologic demonstration of Negri bodies in Brain.
A case of rabies is mainly diagnosed on clinical history of dog bite and specific physical signs and symptoms (Mental Excitement, Hydrophobia, spasms or Paralysis). It has to be differentiated from Hysteria, Mania and encephalitis. Confirmation is done by laboratory investigations.
Once rabies has developed treatment is symptomatic. Patient should be nursed in a dark room protected from external stimuli, bright light and noise. Attention should be paid to nutrition, Hydration and electrolyte disturbances. Diazepam and chlorpromazine are employed intravenously every 4-6 hrly to sedate and relax the patient.
Cardio-respiratory support should be given and regular monitoring done. Persons attending on hydrophobia patient should take all precautions to see that they do not accidentally come in touch with the saliva of the patient on any fresh cut or abrasion.
Prevention of rabies in Man
It consists of the following steps:
1. Management of the wound
2. Post exposure immunization
3. Pre-exposue immunization.
Local treatment of wounds, scratches and licks
It is important to thoroughly clean the wound with soap and water. Appropriate cleaning measures reduces the risk of rabies by lowering the infective virus load on the injury site. Cauterization is not recommended. Apply either alcohal (40-70%) or CETAVLON on the wound. Bites should not be sutured.
If patient has not been actively immunized against tetanus, tetanus toxiod be administered. To prevent sepsis in the wound a course of antibiotics is recommended. If it is severe, Local injection of antirabies serum of hyperimmune globulin at the site of wound is recommended. It shall reduce the risk further.
Post exposuit immunization
It is important to assess the risk to the person who has been bitten or licked by an animal (Cat, Dog). The risk is maximum if the scratches or bites are near the face, neck or head. The animal shows odd behavior and presents with clinical signs of rabies. This is even true for those where laboratory tests fail to confirm the diagnosis.
This is achieved by anti- rabies vaccination which affords protection lasting for 6 months. The various vaccines are:
This vaccine is prepared from sheep brains that are infected with modified rabies. It is inactivated by phenol (SEMPLE) or beta propiolactone (BPL). It is injected subcutaneously on the abdominal wall muscles. Dosage and duration of treatment depends on the degree of risk.
Classification of exposure
Class 1: Slight or negligible exposure. Minimal risk. All cases of licks.
Class 2: Moderate exposure. All bites except those on the head, neck, face. Licks, fresh cuts and scratches drawing blood.
Class 3: Severe exposure. All bites on the neck or above. Palms and fingers, lacerated wounds. Bites by wild animals
Complications following this are of two types. Local at the site of injection like pain, tenderness and itching. Systemic reactions such as fever, headache, insomnia and palpitation. But the most serious complication is neuroparalytic reactions which generally occur by the 6th or 7th injection.
It is often preceded by prodromal symptoms. Neurological involvement includes temporary paralysis of one or more cranial nerves, laundry type of paralysis of limbs, encephalitis and ascending paralysis.
Attenuated viral vaccines
These are produced in human diploid cell strain (HDCS) purified chick embryo cells (PCEC) and purified vero cells (PURV).
Purified chick embryo cell rabies vaccine is prepared from FLURY strain of rabies virus which after growth is inactivated by beta propiolactone (BPL). It is a potent one and is virtually free of side effects. Six-seven dose schedule spread over a period of three months is recommended.
A person bitten by a rabid animal is given six doses of lml each on days 0, 1, 3, 7, 14, 30 another injection after 90 days may be given. The dose is 1 nfl irrespective of age and weight. Human diploid cell vaccine (HDCV) and Duck Embryo vaccines (DEV) are other alternatives available. Reactions to these are uncommon.
This is given to persons with high risk of contracting rabies like veterinary surgeons, animal trainers and laboratory workers. Generally three injection of vaccine are given at 0, 7 and 21 days. Protection lasts for up to 3 years.
Immediate protection after bite is provided by Human Rabies immune globulin (HRIG) in a total dose of 20 units per kg body weight. Half of the total dose is infiltrated locally at the wound site and rest given by intramuscular injection. The passive immunity persists for 2 weeks.
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