Rabies

Disease Occurrence and Public Health Significance

• Australia is free from terrestrial rabies
• Only two confirmed human cases in Australia, both contracted overseas (1990 and 1987)
• Rabies is endemic in:
  • Asia (59.6% of global cases)
  • Africa (36.4% of global cases)
  • North and South America
  • Parts of Europe
• 99% of cases are transmitted by dogs
• 59,000 deaths per year worldwide
• 40% of cases occur in children under 15
• Estimated annual global financial burden: US$8 billion
• Most human deaths follow dog bites for which adequate post-exposure prophylaxis (PEP) was not or could not be provided
• PEP initiated at an early stage using rabies vaccine and rabies immunoglobulin may be 100% effective in preventing rabies-related deaths

Australian Bat Lyssavirus (ABLV)

• Unique to Australia, first identified in 1996
• Three human cases reported, all fatal (1996, 1998, and 2013)
• Found in:
  • All four species of flying foxes
  • Seven genera of insectivorous bats
• Low prevalence in wild bat population (less than 1%)
• Higher risk in:
  • Sick, injured, or orphaned bats
  • Bats with neurological signs
• Evidence suggests ABLV infection is more common in bats with neurological signs

Transmission

• bite or scratch from an infected animal, usually dogs, but also cats, bats and other wildlife
• body fluids from an infectious animal coming into contact with an individual’s mucous membranes.

• Children commonly bitten

Incubation

• Usually 3-12 weeks
• on average
  • dog incidents was 27.4 weeks
  • bat incidents was 10.5 weeks
• may range from four days to 19 years
• in more than 93% of patients, the onset is within one year of exposure
• Once the virus has entered the body it replicates in muscle cells near the entry wound.
• Virions penetrate nerve endings and travel in the axoplasm to the spinal cord and brain. 
• When in the central nervous system the viruses again replicate before they spread to the salivary glands, lungs, kidneys and other organs via the autonomic nerves.

Clinical

• at the inoculation site
  • Paresthesia
  • Pain
  • intense itching 
• prodromal symptoms may mimic systemic viral infections – malaise, fever, anorexia, nausea

Acute neurological phase

• follows 2-10 days after the prodromal symptoms (virus manifests itself in the central nervous system)

• 2 forms
  • Furious rabies – also known as classical rabies
    • muscular fasciculations
    • seizures
    • aphasia
    • Hydrophobia and aerophobia
      • pathognomonic for rabies
      • occur in 50% of patients
      • due to severe laryngeal or diaphragmatic spasms and a sensation of asphyxia. 
      • Due to violent response of the airway irritant mechanisms. 
      • Even the suggestion of drinking may induce hydrophobic spasm.
    • Autonomic instability
      • Fever
      • Tachycardia
      • Hypertension
      • Hyperventilation
    • Bhavioural
      • episodic delirium
      • psychosis
      • restlessness
      • thrashing
  • Dumb rabies – the paralytic variety
    • Paralysis : Symmetrical, generalized or ascending, may be mistaken for Guillain-Barré syndrome.
    • sensory system spared
    • Calm clarity gradually progresses to delirium, stupor, and then coma
• progression towards coma and death occurs within 1-2 weeks from the onset of neurological dysfunction

Management after development of symptoms

• Need
  • pre-exposure prophylaxis (PrEP)
  • timely adequate post-exposure prophylaxis(PEP)

Treatment

• seek medical advice immediately, even if you have been vaccinated
• Pregnancy is not a contraindication to postexposure prophylaxis against rabies, which is warranted to protect the life of the fetus and mother
• Proper cleansing of the wound is the single most effective measure for reducing transmission.
  • immediately wash the wound thoroughly with soap and water for at least 10-15 minutes. 
  • If available, an antiseptic with anti-virus action such as betadine/iodine or alcohol (ethanol) should be applied after washing. 
  • If animal saliva contacts the eyes, nose or mouth, it is necessary to flush the area thoroughly with water

post-exposure prophylaxis(PEP)

• human rabies immune globulin (HRIG) withing 48hrs +  vaccine dose on same day or at least within 7 days
• HRIG is often difficult to obtain in many overseas countries, and if this is the case, it is important that the traveler returns to Australia to obtain HRIG as soon as possible.
• death is almost always inevitable in patients who develop neurological signs and symptoms due to treatment failure or non-immunisation only Psupportive measures are recommended
• alliative measures such as sedation and physical and emotional support is recommended since patients tend to be severely agitated and anxious respiratory, cardiovascular and nutritional support may be necessary.

 Lyssavirus exposure categories

Type of exposure***	Description
Category I	Touching or feeding anima​ls, licks on intact skin, as well as exposure to blood, urine or faeces**
Category II	Nibbling of uncovered skin, minor scratches or abrasions without bleeding
Category III	Single or multiple transdermal bites or scratches, contamination of mucous membrane or broken skin with saliva from mammal licks, exposures due to direct contact with bats in situations where bites or scratches may not be apparent****

Rabies post-exposure prophylaxis: terrestrial animal exposures

Rabies post-exposure prophylaxis: bat exposures

Prevention

Pre-exposure vaccination (PrEP) recommended for high-risk groups

• Groups include:
  • Bat handlers
  • Veterinarians
  • Wildlife officers
  • Veterinary nurses
  • Zoo keepers
  • Wildlife researchers
  • Laboratory personnel working with live lyssaviruses
  • Expatriates and travelers (following a risk assessment) who will be spending time in rabies-enzootic areas
  • People working with mammals in rabies-enzootic areas
• Two rabies vaccine preparations available in Australia:
  • Human diploid cell vaccine (HDCV)
  • Purified chick embryo cell vaccine (PCECV)
• Pre-exposure vaccination consists of 3 doses on day 0, day 7, and day 21-28
• Booster doses recommended for ongoing occupational exposure risk
• Intramuscular (IM) route of administration preferred
• Intradermal route may be used as PrEP by suitably qualified and experienced providers as an ‘off-label’ use

Handling Bats

• Only appropriately vaccinated and trained people should handle bats
• Members of the public should not attempt to handle bats
• Use appropriate personal protective equipment (PPE) to avoid bites and scratches, including:
  • Puncture-resistant gloves and gauntlets
  • Long sleeved clothing
  • Safety eyewear or face shield
  • Towel to hold the bat
• Dispose of dead bats safely using gloves and a tool

Travel Advice

• Avoid close contact with bats worldwide
• Avoid close contact with wild or domestic terrestrial mammals (especially dogs, cats, and monkeys) in rabies-enzootic regions
• Know what to do if bitten or scratched by a mammal while abroad
• Obtain written details on any post-exposure management provided overseas
• Parents: ensure children are careful around mammals, as they are at higher risk of bites to the face and head
• Consider rabies pre-exposure vaccination (or booster doses) pre-travel if:
  • Risk assessment indicates high risk of exposure
  • Ease of access to PEP is limited
  • Interaction with mammals is likely (based on accommodation and planned activities)

Note: PEP stands for Post-Exposure Prophylaxis, which includes wound cleaning, vaccination, and in some cases, rabies immunoglobulin.

pre-exposure prophylaxis (PrEP)

• 3 dose course 0,7 and 28 days
• Variable between countries
• Booster doses/serology if repeated exposures
• Cost $110
• Considerations:
  • People who work with bats (bat handlers, veterinarians, wildlife officers, zookeepers)
  • Laboratory workers who work with live lyssaviruses
  • Travelers to rabies-enzootic regions (based on risk assessment)
  • Person’s circumstances and personal preferences