Rabies

Rabies is a major problem in some countries, and established infection is invariably fatal. It is a genotype 1, single-stranded RNA virus of the Lyssavirus genus. The rabies virus is bullet-shaped and has spike-like structures arising from its surface containing glycoproteins that cause the host to produce neutralizing, haemagglutination-inhibiting antibodies. The virus has a marked affinity for nervous tissue and the salivary glands. It exists in two major epidemiological settings:
Urban rabies is most frequently transmitted to humans through rabid dogs and, less frequently, cats.

Sylvan (wild) rabies is maintained in the wild by a host of animal reservoirs such as foxes, skunks, jackals, mongooses and bats.
With the exception of Australia, New Zealand and the Antarctic, human rabies has been reported from all continents. Transmission is usually through the bite of an infected animal. However, the percentage of rabid bites leading to clinical disease ranges from 10% (on the legs) to 80% (on the head). Other forms of transmission, if they occur, are rare.

Having entered the human body, the virus replicates in the muscle cells near the entry wound. It penetrates the nerve endings and travels in the axoplasm to the spinal cord and brain. In the CNS the virus again proliferates before spreading to the salivary glands, lungs, kidneys and other organs via the autonomic nerves.

There have been only two recorded cases of survival from clinical rabies.

Clinical features

The incubation period is variable and may range from a few weeks to several years; on average it is 1-3 months. In general, bites on the head, face and neck have a shorter incubation period than those elsewhere. In humans, two distinct clinical varieties of rabies are recognized:

furious rabies - the classic variety

dumb rabies - the paralytic variety.

Furious rabies

The only characteristic feature in the prodromal period is the presence of pain and tingling at the site of the initial wound. Fever, malaise and headache are also present. About 10 days later, marked anxiety and agitation or depressive features develop. Hallucinations, bizarre behaviour and paralysis may also occur. Hyperexcitability, the hallmark of this form of rabies, is precipitated by auditory or visual stimuli. Hydrophobia (fear of water) is present in 50% of patients and is due to severe pharyngeal spasms on attempting to eat or drink. Aerophobia (fear of air) is considered pathognomonic of rabies. Examination reveals hyperreflexia, spasticity, and evidence of sympathetic overactivity indicated by pupillary dilatation and diaphoresis.

The patient goes on to develop convulsions, respiratory paralysis and cardiac arrhythmias. Death usually occurs in 10-14 days.

Dumb rabies

Dumb rabies, or paralytic rabies, presents with a symmetrical ascending paralysis resembling the Guillain-Barre syndrome. This variety of rabies commonly occurs after bites from rabid bats.

Diagnosis

The diagnosis of rabies is generally made clinically. Skin-punch biopsies are used to detect antigen with an immunofluorescent antibody test on frozen section. Viral RNA can be isolated using the reverse transcription polymerase chain reaction (RT-PCR). Isolation of viruses from saliva or the presence of antibodies in blood or CSF may establish the diagnosis. The corneal smear test is not recommended as it is unreliable. The classic Negri bodies are detected at post-mortem in 90% of all patients with rabies; these are eosinophilic, cytoplasmic, ovoid bodies, 2-10 nm in diameter, seen in greatest numbers in the neurones of the hippocampus and the cerebellum. The diagnosis should be made pathologically on the biting animal using RT-PCR, immunofluorescence assay (IFA) or tissue culture of the brain.

Treatment

Once the CNS disease is established, therapy is symptomatic as death is virtually inevitable. The patient should be nursed in a quiet, darkened room. Nutritional, respiratory and cardiovascular support may be necessary.

Drugs such as morphine, diazepam and chlorpromazine should be used liberally in patients who are excitable.

Prevention

Pre-exposure prophylaxis.

This is given to individuals with a high risk of contracting rabies, such as laboratory workers, animal handlers and veterinarians. Two doses of human diploid cell vaccine (HDCV) 1.0 mL deep subcutaneously or intramuscularly given 4 weeks apart provides effective immunity. A reinforcing dose is given after 12 months and additional reinforcing doses are given every 1-3 years depending on the risk of exposure. Vaccines of nervous-tissue origin are still used in some parts of the world. These, however, are associated with significant side-effects and are best avoided if HDCV is available.

Postexposure prophylaxis.

The wound should be cleaned carefully and thoroughly with soap and water and left open. Human rabies immunoglobulin should be given immediately (20 IU/kg); half should be injected around the area of the wound and the other half should be given intramuscularly. Five 1.0 mL doses of HDCV should be given intramuscularly: the first dose is given on day 0 and is followed by injections on days 3, 7, 14 and 28. Reaction to the vaccine is uncommon.

Control of rabies

Domestic animals should be vaccinated if there is any risk of rabies in the country. In the UK, control has been by quarantine of imported animals and no indigenous case of rabies has been reported for many years. The quarantine laws are under revision at the present time. The Pet Travel Scheme (PETS) introduced as a pilot scheme in 2000 enables certain pet animals to enter or re-enter Great Britain without quarantine if they come from qualifying countries via designated routes, are carried by authorized transport companies, and meet the conditions of the scheme. Wild animals in 'at risk' countries must be handled with great care.