• The first symptoms of rabies usually begin when the virus enters the CNS. A non-specific prodrome of 2-10 days includes fever, malaise, fatigue, anorexia, cough, sore throat, abdominal pain, nausea, vomiting or diarrhoea. The first rabies-specific symptom is pain or paraesthesia referred to the site of the exposure.
• The acute neurological period manifests as either a hyperactive (furious rabies) in 80% or a paralytic (dumb rabies) form in 20%. Autonomic instability is often prominent (hyperthermia, salivation, hypertension and tachycardia).
• The neurological phase lasts 2-7 days before development of coma then death.
  

No tests are available to diagnose human rabies during the incubation period.

After onset of clinical disease, diagnostic methods include:

• Direct fluorescent antibody staining of skin biopsy from nape of neck (50%).
• Rabies neutralising antibodies in serum or CSF.
• Rabies virus isolation from saliva, CSF, urine and tracheal secretions (low).
• Rabies RT-PCR in saliva, CSF, urine and tissue.
• Cortical brain biopsy.
• Specimens may need to be sent overseas for tests.
• Post-mortem brain examination for Negri bodies and fluorescent staining for rabies antibodies.

Notify all suspected and confirmed cases immediately. Call MOH Communicable Diseases Surveillance team at 98171463 and the Agri-Food and Veterinary Authority of Singapore (AVA) for further investigation.

• There is no specific treatment for clinical human rabies. Intensive supportive care in the ICU is often used although mortality is virtually 100%.
• Standard and respiratory precautions should be observed by healthcare workers caring for such patients. Pre-exposure immunisation of medical staff is generally not required. Routine delivery of healthcare is not an indication of post-exposure prophylaxis unless the healthcare worker is reasonably certain that he or she was bitten or mucous membranes or non-intact skin was exposed to potentially infectious saliva or neural tissue.

• In rabies-free Singapore, the AVA exercises strict control on importation and quarantine of dogs, cats and wild animals and intensive control of stray dog and cat population.
• In the case of human exposure to animals suspected of having rabies, immediate attempts should be made to identify, capture or kill the animal involved. The veterinarian, AVA, will remove the brain of the animal to examine for presence of rabies virus antigen by immunofluorescence.

Pre-Exposure Vaccination

• For travellers visiting rabies endemic countries (Central and South America, Africa, Indian subcontinent and Southeast Asia), pre-exposure vaccination may be recommended depending on intended activity, duration of stay, local incidence of rabies and availability of appropriate anti-rabies biologicals.
• Pre-exposure vaccination greatly simplifies but does not eliminate the need for post-exposure treatment.
• Pre-exposure vaccination consists of 3 doses given on days 0, 7 and 21 or 28 days.
• The human diploid cell vaccine (HDCV) is an inactivated virus vaccine available in Singapore.

Post-Exposure Treatment

• The most effective mechanism of protection against rabies is to wash and flush a wound or point of contact with soap and water, followed by application of ethanol, tincture or aqueous solution of iodine.
• Suturing should be postponed and where indicated, anti-tetanus toxoid and antimicrobials should be administered.
• Rabies vaccine and immunoglobulin should be given as soon as possible if indicated (see table below). Post-exposure vaccination consists of 5 doses given on days 0, 3, 7, 14 and 28. Tan Tock Seng Hospital, keeps a stock of rabies vaccine and human rabies immunoglobulin.

1. Source: Rabies pre- and post-exposure prophylaxis in humans (revised 15 June 2010). Dept of Neglected Tropical Diseases. Neglected Zoonotic Diseases team. WHO, Geneva. Exposure to rodents, rabbits and hares seldom, if ever, requires specific anti-rabies treatment.
2. If an apparently healthy dog or cat in or from a low-risk area is placed under observation, it may be justified to delay specific treatment.
3. This observation period applies only to dogs and cats. Except in the case of threatened or endangered species, other domestic and wild animals suspected as rabid should be euthanised and their tissues examined using appropriate laboratory techniques.