Rabies Flashcards
Rabies is caused by the rabies virus, genus Lyssavirus and family Rhabdoviridae. The genus Lyssavirus consists of over 80 viruses. There are about 10 viruses in the rabies serogroup, most of which only rarely cause disease in humans. The most common cause of rabies is the genotype 1 virus (classical rabies virus)
What is nucleic acid/ virus structure?
-ssRNA
bullet-shaped
three component parts:
Surface glycoprotein (G protein).
Outer envelope (matrix protein).
Nucleocapsid.
How is it transmitted?
What is incubation period?
Saliva from bite of infected animal through broken skin
Can be exposure on mucus membrane
Occasionally droplet spread - such as in bat cave
Any mammal can carry rabies - 99% of human cases due to dog bite. UK is rabies free
3-12 weeks incubation
What is the pathophysiology once inoculation has occurred?
The virus enters the peripheral nerves. The virus is highly neurotropic and avoids immune defences by invading neural tissue.
The virus then incubates for a period of time which reflects size of inoculum and distance to the central nervous system. The incubation period is usually between 3 and 12 weeks but can range from 4 days to 19 years. In 90% of cases incubation is less than 1 year.
Shorter incubation periods are seen in those with multiple, severe wounds (particularly of the head, which is richly innervated), in children, and when post-exposure treatment fails.
Amplification occurs until the single-stranded RNA nucleocapsid core spills into myoneural junctions, entering both motor and sensory axons. Prophylactic therapy at this point is futile and the disease advances with a uniformly fatal course. Moving along axons is slow, so has long incubation period. HSV moves along microbtubules and can infect faster
The virus spreads in a retrograde manner along axons (at about 1-2 cms per day) and enters spinal ganglions.
Multiplication of the virus in the ganglions is marked by onset of pain or paraesthesia at the inoculation site. This is a hallmark symptom.
Spread through the nervous system is now more rapid (at about 30 cms per day) and marked by a progressive encephalitis.
Finally, the virus spreads peripherally, including to the salivary glands
What symptoms occur?
General - Pain/ parasthesia around wound fever headache hallucinations coma
Furious rabies 2/3 of cases. Negri bodies found in brain neurones due to inflammation - agitation hyperactivity hydrophobia photophobia
Paralytic rabies. Inflammation of spinal cord -
ascending paralysis spreads rapidly and symmetrically - can be mistaken for GBS
Survive 2-12 days once symptoms develop
What is important about history from patient/ animal?
Type and site of exposure. Bites are higher risk than scratches; head and neck injuries are higher risk than distal injuries.
Vaccination history
Animal involved: species and current state of health. It is important to determine the vaccination status of the animal where possible. For domestic animals, if the animal can be observed and remains well and behaves normally 15 days after the date of an exposure it will not have had rabies infection at the time of exposure. Decisions about the need for post-exposure treatment within the 15 days will depend on other risk factor assessment. Bats can be asymptomatic and transmit. May need to examine dead animal
How to diagnose rabies?
Nuchal biopsy - tissue immunoflourescence for antibody testing
Blood/ saliva/ CSF PCR or antibody testing
What is management of following suspected rabies exposure?
Wound cleansing, including with Human rabies specific immunoglobulin (HRIG). If cannot infiltrate all HRIG, then can inject rest IM, but not in same site as vaccine, as will neutralise. Can give HRIG up to 7 days after infection, even if vaccine given
If mucus membrane exposure - give HRIG all IM, as cannot infiltrate
HRIG 20 IU/kg
Avoid suturing wound until HRIG given
Rabies vaccine - aim to give within 12 hours
Tetanus - do not forget
PEP includes use of rabies vaccine, and HRIG in non-immunised individuals, whilst awaiting antibody response.
What is PEP guidance from PHE?
Low risk unvaccinated High risk unvaccinated Low risk vaccinated High risk unvaccinated Immunocompromised
Vaccinated includes having completed 3 doses of rabies vaccine
Depends on -
- country risk - low if only occurs in wild animals/ high if occurs in pets
- species of animal
- site infected
UK is considered “no risk” country, and so will not require PEP in almost all cases.
Low risk unvaccinated
- 4 doses rabies vaccine on days 0, 3, 7, 21
High risk unvaccinated
- 4 doses rabies vaccine on days 0, 3, 7, 21
PLUS HRIG on day 0 only
Low risk vaccinated
- 2 doses on days 0 and 3-7
High risk vaccinated
- 2 doses on days 0 and 3-7
If immunocompromised - if low or high risk will receive HRIG and 5 vaccine doses
Useful pages -
- Green book PHE chapter 27
- Rabies post-exposure risk assessment and calculator
- Summary of risk assessment and treatment Annexe 3
Usually HRIG/ vaccines supplied the next day
Days of vaccination may not necessarily be the same as days of exposure.
How to prevent/ reduce rabies transmission?
Avoidance of contact with potentially rabid animals.
Vaccination of domestic dogs, cats and ferrets
Euthanasia of unvaccinated pets in contact with a rabid animal (or six months’ isolation, and vaccination one month prior to release).
The Pet Travel Scheme - animals entering the UK have to have proof of rabies vaccination and subsequent immunity
Vaccinate high risk populations - vet worker, bat handlers, lab staff, traveller endemic area
What is rabies vaccination schedule for high risk group?
Non-post exposure prophylaxis group
Inactivated vaccine on day 0, 7, 28
Last dose can be day 21 if absolutely required
IM injection
What if rabies vaccine cannot be given on certain days due to patient/ hospital issues?
If difficult to get timing of vaccines correct, can give +/- 1 day
Positive rabies case, which authorities need to be informed?
PHE - notifiable disease
Defra - will send vet to check animal. Notifiable disease in animals