Rabies

Rabies is an acute, progressive, almost universally fatal viral encephalomyelitis caused by rabies virus, a neurotropic lyssavirus. It is transmitted through the bite or, less commonly, mucous membrane or open wound exposure to saliva of an infected mammal. These are most commonly dogs in endemic regions worldwide and bats in regions with effective canine rabies control.

It is one of the few conditions where death is essentially certain once clinical symptoms develop. Immediate and appropriate post exposure prophylaxis following any potential exposure is therefore the single most critical management intervention. It is uniformly effective if given correctly and promptly, before symptom onset.

Pathophysiology

Following inoculation, the virus replicates locally before entering peripheral nerve endings. It then travels retrogradely along axons to the central nervous system. This typically takes weeks to months (the incubation period).

The incubation period varies considerably according to the site and severity of the bite. It is shorter with bites closer to the head and with heavier viral inoculation.

During this time the virus is not detectable and the patient remains entirely asymptomatic. This provides the window of opportunity during which post exposure prophylaxis remains effective.

A non specific prodrome of fever, malaise, headache and, characteristically, pain, paraesthesia or itching at the original bite site (reflecting viral replication and inflammation at the site of initial peripheral nerve entry) precedes the onset of overt neurological disease by several days.

Encephalitic (furious) rabies is the commoner presentation. It is characterised by:

• hyperactivity and agitation
• hydrophobia: severe pharyngeal spasm triggered by attempts to swallow water, a highly characteristic though not universal feature
• aerophobia: similar spasm triggered by a draught of air
• fluctuating consciousness

It progresses to coma and death, typically within one to two weeks of symptom onset.

Paralytic (dumb) rabies presents with an ascending flaccid paralysis, resembling Guillain Barré syndrome, without the prominent hydrophobia and agitation of the encephalitic form, and is more frequently misdiagnosed given this atypical presentation, though follows a similarly fatal course.

Once clinical symptoms of either form have developed, the disease is essentially always fatal, with only a small number of survivors ever documented worldwide, generally following intensive experimental treatment protocols with uncertain and inconsistent efficacy.

Antemortem diagnosis in a symptomatic patient can be supported by detection of viral ribonucleic acid using reverse transcriptase polymerase chain reaction on saliva, skin biopsy from the nape of the neck (examining hair follicle innervation for viral antigen), or cerebrospinal fluid. Serum and cerebrospinal fluid antibody testing also supports the diagnosis.

The diagnosis is frequently made clinically in the appropriate epidemiological context, given the characteristic and distinctive presentation.

The most critical diagnostic assessment in practice is not confirmation of established disease. It is careful risk assessment of any reported animal exposure. This assessment directly determines the need for post exposure prophylaxis.

Evaluate:

• the species involved
• the nature of the exposure (bite, scratch, or mucous membrane or open wound contact with saliva)
• the vaccination and observable behaviour of the animal where known
• local epidemiology

Immediate, thorough wound washing is the first and one of the most effective interventions following any potential rabies exposure. Wash with soap and water (or a virucidal agent such as povidone iodine solution where available) for a minimum of fifteen minutes. This substantially reduces viral load at the inoculation site.

Perform it regardless of how much time has elapsed since the exposure.

Post exposure prophylaxis comprises both passive and active immunisation. In a previously unvaccinated individual, initiate it as soon as possible following any category two or category three exposure according to World Health Organization categorisation:

• category two: minor scratch or abrasion without bleeding, or contact of broken skin with saliva
• category three: single or multiple transdermal bites or scratches, contamination of mucous membranes with saliva, or exposure to a bat

Human rabies immunoglobulin 20 international units per kg (or equine rabies immunoglobulin 40 international units per kg where human immunoglobulin is unavailable) is infiltrated as thoroughly as anatomically possible into and around the wound. Any remaining volume is given intramuscularly at a site distant from the vaccine administration site. It provides immediate passive protection while active immunity develops.

It is indicated for all category three exposures in a previously unvaccinated individual.

It should not be given at all to a patient who has previously completed a full pre or post exposure vaccination course, since it can suppress the anamnestic vaccine response in this circumstance.

Rabies vaccine (cell culture derived vaccine) is given intramuscularly into the deltoid, never the gluteal region, given reduced immunogenicity at that site. It is given according to an established schedule:

• the Essen regimen, most commonly: five doses given on days zero, three, seven, fourteen and twenty eight
• the abbreviated four dose Zagreb regimen: two doses given on day zero (one in each deltoid) followed by single doses on days seven and twenty one

Both regimens provide equivalent protective efficacy.

Previously vaccinated individuals (those with a documented complete prior pre or post exposure course) require only two booster doses of vaccine, given on days zero and three, without the need for rabies immunoglobulin, reflecting the more rapid anamnestic immune response in an already primed individual.

Pre exposure prophylaxis comprises two doses of vaccine given on days zero and seven. It is recommended for individuals at ongoing occupational or travel related risk (veterinarians, laboratory workers handling the virus, and travellers to highly endemic areas with limited access to prompt medical care).

It simplifies and shortens the post exposure regimen required if a subsequent exposure occurs, and removes the need for immunoglobulin entirely.

Once clinical symptoms of rabies have developed, management is exclusively palliative and supportive. It focuses on comfort and symptom control, given the essentially universal fatality of established disease. Use sedation for agitation and distress, and hold open, honest discussion with the family regarding prognosis.

Aggressive intensive supportive treatment does not alter the outcome in the overwhelming majority of cases, despite occasional isolated reports of survival following intensive experimental protocols.