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Rabies

Overview

Rabies is a serious viral infection which targets the brain and nervous system to produce fatal encephalitis. The virus belongs to the family Rhabdoviridae and genus Lyssavirus. The genus has 6 members but only serotype 1 can cause human disease. Rabies is almost always fatal once symptoms begin to develop, but can be prevented if treatment is administered shortly after exposure to the virus, before it enters the peripheral nerve. Many mammals maintain and transmit the virus, with dogs accounting for 54% of animal cases. The majority of cases in humans occur as a result of a rabid dog bite. Infection causes 60,000 deaths per year, mostly in Asia and Africa which account for 95%. More than 15 million individuals worldwide receive a post-bite vaccination annually.

 

Signs and symptoms

The incubation period for rabies is between 1-3 months but has been reported to vary from less than 1 week to just under a year.

Initial symptoms include:

  • Fever

  • Pain, unusual/unexplained tingling, pricking or burning sensation at the wound site

  • Headache

  • Malaise

  • Vomiting

  • Subtle personality changes

  • Myo-oedema

 

Neurological disease then develops 4-10 days later and lasts between 2-14 days before coma intervenes. Patients die an average of 18 days after the onset of symptoms.

There are two main clinical presentations of neurological disease in rabies.

 

1. Furious (encephalitic) rabies – 80% of cases:

  • Anxiety

  • Biting

  • Hydrophobia as an exaggerated respiratory tract irritant reflex

  • Delirium

  • Agitation

  • Seizures

  • Hyperventilation

  • Pituitary dysfunction – diabetes

  • Cardiac arrhythmias

  • Autonomic dysfunction – papillary dilation, salivation, priapism

  • Aerophobia

 

2. Paralytic rabies – 20% of cases:

  • Muscles gradually become paralysed, starting at the site of the bite/scratch

  • Meningeal signs can develop

  • Coma develops

 

Causes

Rabies is transmitted via the saliva of an infected mammal,

most commonly through a bite or scratch by a dog.

Transmission can also occur through introduction of infected

saliva to human mucosa or an open wound. Dogs account

for human rabies deaths in Africa and Asia, whereas bats are

the main cause for human rabies death in the Americas. In

rare cases, rabies can be contracted through inhalation of

virus-containing aerosol or through transplantation of an

infected organ. Ingestion of infected meat will not cause

human disease.

Once the virus has entered the break in the skin or the

mucosal membrane, it attaches to muscle and nerve cells where it replicates after internalisation. The nerves which innervate the muscle spindle are infected first whilst the virions migrate along the axon, travelling by retrograde axoplasmic flow. When the virus reaches the spinal cord, it spreads throughout the central nervous system to reach the rest of the body through the peripheral nerves. Mechanism of central nervous system damage is unclear but is assumed to interfere with neurotransmission, endogenous opioid systems or act in an excitotoxic manner. Pathological examinations shows furious rabies to present with encephalitis characteristics, whilst paralytic rabies shows inflammation and necrosis of the spinal cord with segmental demyelination.

 

Risk factors / at risk groups

  • Travelling to endemic areas

  • 40% of individuals bitten by a rabid animal are aged under 15

  • Working in a laboratory with the rabies virus

  • Veterinary surgeons or students

  • Activities likely to come into contact with rabid animals                                                                                                      (e.g. exploring caves where bats live)

 

Diagnosis / microbiology testing

  • Direct fluorescent antibody staining of a skin biopsy from                                                                                                       nape of neck – virus localises in hair follicles

  • RT-PCR of tissue

  • CSF lumbar puncture

  • Saliva test

 

Treatment

Post-exposure treatment (PET) should be carried out as soon as possible after the introduction of infection. The wound should be washed thoroughly with running water and 20% soap solution. Antiseptic or alcohol should be used to clean the wound before applying ethanol, tincture or virucidal agent e.g. iodine. The wound should be left open with a simple dressing. Avoid stitching as this could expose nerve endings to the virus. Help should then be sought from the nearest hospital or medical centre.

If not previously vaccinated, rabies immunoglobulin 20IU/kg should be infiltrated around the wound with any remaining dose administered intramuscularly at a site distant from the vaccine administration. The 1.0mL vaccine should then be administered intramuscularly on day 0, 3, 7, 14 and 28.

If the individual was already previously vaccinated, immunoglobulin should not be administered. Instead the vaccine should be given on day 0 and 3.

 

Treatment after onset is generally of no benefit. In 2004, a 15 year old girl survived despite no history of previous vaccination or PET even though symptoms had begun to develop. Her treatment plan consisted of an early induction coma, ventilatory support, ribavirin and amantadine.

 

Vaccine / preventative measures

The rabies vaccine should be administered in every case of suspected rabies exposure. It is also recommended as prophylaxis if the individual is travelling to an endemic area or has potential risk factors. The 1.0mL vaccine is used for prophylaxis and treatment. The 1.0mL vaccine is given intramuscularly on day 0, 7, 21 and 28. There are currently 3 different vaccines available worldwide:

  1. Human diploid cell vaccine (HDCV), created using samples of human cells

  2. Purified chick embryo cell rabies vaccine (PCEC), created using samples of chicken embryos

  3. Nerve tissue vaccine, created using samples of nerves taken from animal brains

 

Preventative measures include:

  • Avoiding endemic areas

  • Do not approach wild animals

  • Report stray animals to local authorities

  • Vaccinate pets or keep them indoors

  • Keep bats out of accommodation

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