RABIES

Rabies is an easily preventable but essentially fatal CNS infection that continues to be a major public health problem in India, accounting for gt;50% of total world cases. Union territories of Lakshadweep and Andaman/ Nicobar islands are free from this disease.

Epidemiology: Rabies, caused by a neurotropic bullet­shaped RNA virus—Lyssavirus seortype 1, is primarily a zoonotic disease of warm-blooded animals. Man is accidentally affected after bite or licks of rabid animals. Dog is the commonest source (99%) in India, though rare cases may involve cats and wild canines, e.g. fox and wolves. Vampire bat-related rabies, common in USA and Latin America, is not reported from India. Barring few anecdotal reports, there is no asymptomatic carrier state and infection is essentially fatal in animals.

Virus is secreted in saliva of rabid animal only from

3- 6 days before the onset of symptoms and hence, human infection is unlikely if the dog survives or remains well till 10 days of biting incident. Less than 50% bites by proven rabid animals result in human rabies. Human- to-human transmission, though theoretically possible, is extremely rare.

Pathogenesis: After inoculation with contaminated saliva, virus replicates in muscles or connective tissue. Unless neutralized at this stage by natural or vaccine induced immune response, it eventually and irreversibly gets attached to the peripheral nerves and development of disease becomes inevitable. Virus spreads centripetally within neuronal sheaths to CNS, mainly involving brainstem, basal ganglia, thalamus and hippocampus, but sparing cerebral cortex (no loss of consciousness).

Neuronal destruction at brain-stem level, including inhibitory neurons to nucleus ambiguous that controls inspiration, is responsible for classical presentation of hydrophobia and inspiratory muscle spasms. Following CNS infection, virus also descends centrifugally along the nerves to distal muscles, skin and saliva.

Clinical manifestations: Incubation period is extremely variable, ranging from 4 days to 7 years (usual: 20-60 days), being shorter in children, facial bites and after severe mauling. Clinical progression is also variable, but may be divided into:

• Prodromal phase (2-10 days), with—(i) pain, pruritus or paresthesias at wound site, (ii) mental changes, e.g. apprehension, anxiety or agitation and (iii) non­specific symptoms, e.g. mild fever, headache, vomiting, etc.

• Acute neurological phase (2-21 days) is of furious (80%) or paralytic (20%) variety, characterized by:

- Pathognomonic hydrophobia or aerophobia, i.e. reflex spasms of pharyngeal and neck muscles, during swallowing, wind-movement, etc.

- Intermittent bizarre hyperactivity or combative acti­vity in furious variety, with intervening lucid periods and typical apprehensive appearance.

- Ascending asymmetrical flaccid paralysis, in paralytic variety.

• Terminal phase, characterized by increasing frequency of unprovoked spasms, opisthotonus, labored breathing, hypoxic coma and ultimately, cardio­respiratory arrest. Death is inevitable, though a few unconfirmed survivors have been reported among those who were vaccinated before the exposure.

Diagnosis is mainly clinical, based on history of dog bite and typical presentation. Antemortem laboratory diagnosis, though rarely needed, is possible by:

• Antigen detection using fluorescent antibodies (immunofluorescence) in corneal scrapping, skin biopsy from hairline or saliva, and

• Presence of neutralizing antibodies gt;100 IU/ml in CSF or serum after 10 th day of illness.

Presence of Negri bodies—a cytoplasmic inclusion containing clumped viral nucleocapsid in neurons, confirms the diagnosis after death. However, absence of these bodies does not exclude the diagnosis.

D/D of furious rabies includes viral encephalitis (loss of sensorium), tetanus (trismus) and hysteria; while paralytic variety may be confused with other causes of acute flaccid paralysis, e.g.

a. Isolation in a quiet room, protected from external stimuli, e.g. light, sound, etc. to prevent spasms,

b. Sedatives and muscle relaxants to reduce anxiety/ spasm,

c. Parenteral hydration and nutrition, and

d. Cardiorespiratory support, till possible.

Since these cases are potentially infectious (from a week before the onset of symptoms to death), self protection of health staff by gloves, masks, etc. And proper disposal of contaminated fomites and biological fluids is advisable. However, man-to-man transmission is virtually unknown.

Prevention of rabies may be divided into:

• Primary prevention by

- Avoidance of contact with potentially rabid dogs,

- Vaccination of pets, and

- Pre-exposure prophylaxis (PrEP) of occupation- exposed personals, e.g. animal handlers, veteri­narians, forest workers, etc. with two doses of single site IM or two-site ID tissue-culture vaccine (IM 1.0 ml/ID 0.1 ml) on day 0 and 7 are recommended by WHO and IAP. However, total three IM/ID doses are used for pre-exposure prophylaxis in national rabies prophylaxis program, given on day 0, 7, and 21/28.

PrEP is generally not required in children, though IAP recommends it after discussion with parents, in view of higher risk of exposure in Indian children.

• Secondary (post-exposure) prophylaxis is the key of survival after potential rabid bite, discussed below.