Rabies is a fatal viral infection, which is usually acquired in humans from the bite of an infected animal. Nearly all deaths from rabies in humans worldwide result from the bite of a rabid dog.
In the UK, deaths from classical rabies continue to occur in people infected abroad. However, it is rare with only 25 deaths since 1946. No indigenous cases have been reported in the UK other than from bats since 1902, and only one of these has been reported. Worldwide, however, it is a vast problem with over 60,000 deaths each year.
Effective immunisation is available and schedules have been developed for pre-exposure and post-exposure prophylaxis. There is no specific treatment for rabies, and death is almost inevitable once the clinical features present.
- Infection results in encephalomyelitis.
- The incubation period is usually 3-12 weeks but the range is 4 days to 19 years.
- Onset is insidious - wound paraesthesia, headache, fever, malaise.
- Progression is to hydrophobia, hallucinations, paralysis and coma.
- Death results from respiratory paralysis.
For further information, see the separate article Rabies.
Currently cell-culture derived vaccines are used. There are two licensed for use in the UK:
- Human diploid cell vaccine (HDCV), or Rabies Vaccine BP.
- Purified chick embryo cell (PCEC) rabies vaccine, or Rabipur®.
These vaccines are freeze-dried, inactivated and contain traces of neomycin. They should be stored at 2-8°C and discarded if unused one hour after reconstitution. Administration is usually intramuscular in the deltoid region. They can be used interchangeably. Other cell culture-derived vaccines are available elsewhere in the world, which are World Health Organization (WHO) approved.
Each dose, for both pre- and post-exposure prophylaxis is 1 ml (2.5 IU) of rabies vaccine, when given by the intramuscular route.
The Joint Committee on Vaccination and Immunisation recommends the intramuscular rather than the intradermal route for rabies vaccine. The use of the intradermal route is not covered by the manufacturers' product licence and, if it is used, becomes the doctor's own responsibility.
Rabies specific immunoglobulin
Human rabies-specific immunoglobulin (HRIG) is available and is derived from the plasma of immunised human donors for passive immunisation. This is sourced from outside the UK due to the theoretical risk of variant Creutzfeldt-Jakob disease (vCJD) from plasma products.
HRIG is used after high-risk exposure to rabies and is given at the same time as rabies vaccine (at a different site) to give rapid protection until the rabies vaccine becomes effective. It is infiltrated in and around the cleansed wound, or intramuscularly into the antero-lateral thigh. It can be given for up to seven days after starting the vaccination course (active immunisation). The dose is HRIG 20 IU/kg body weight.
It should be stored at 2-8°C.
Recommendations: pre-exposure prophylaxis
This is available free on the NHS to:
- Laboratory workers handling the virus.
- Workers handling imported animals.
- Any handlers of species of bats.
- Animal control and wildlife workers, veterinary staff or zoologists who travel regularly in rabies-enzootic areas.
- Health workers in rabies-enzootic areas who will be at risk of direct exposure to body fluids or tissue from a patient with confirmed or probable rabies.
This does NOT include veterinary practice staff, unless they regularly handle bats or regularly handle imported animals in animal quarantine centres, zoos or ports.
It is also recommended, but not free on the NHS, to travellers to high-risk areas:
- Who are staying for more than one month
- Who are engaging in higher-risk activities, such as cycling or running
- Where there is limited access to medical care and particularly to easy post-exposure prophylaxis
Up-to-date information on specific countries can be found on the NaTHNaC website, the PHE website and the Health Protection Scotland website (Travax and fitfortravel).[4, 5, 6] Children are thought to have a higher risk as they are more likely to approach animals without caution. Essentially the decision to vaccinate results from an individual risk assessment based on the duration of stay, the likelihood of engagement in at-risk activities, the age of the traveller, the rabies endemicity and access to appropriate medical care in the country of destination.
- Primary, pre-exposure protection: give three doses, 1 mL - intramuscular deltoid region - at days 0, 7 and 28. The third dose can be given on day 21 if time is limited.
- A single reinforcing dose is then given, one year after the primary course has been completed, to those at regular risk. In this category of at-risk individuals, boosters at 3- to 5-yearly intervals based on serology should be considered.
- For those who are travelling again to a high-risk area, a booster dose can be considered at ten years after the primary course has been completed.
- Serological testing is only advised for those at continuous or frequent risk:
- In those who work with the live virus, antibodies should be tested every six months. Those people with low levels of antibodies should be given a reinforcing dose of vaccine as necessary to maintain their immune status. The World Health Organization (WHO) currently considers a minimal acceptable antibody titre to be 0.5 IU/mL.
- In those at frequent risk, who have had a booster after one year, serology every 3-5 years should be considered, and boosters given where needed.
Post-exposure prophylaxis is nearly 100% effective at preventing rabies.
The schedule used depends on:
- Level of risk (low, medium or high) in the country.
- Type of exposure (history of the animal/stray, likelihood of infection, etc).
- The individual's immunity (details of previous vaccinations, if any).
If possible, expert advice on the appropriate management and schedule should be sought with this outline of information from:
- In England, the Public Health England (PHE) Virus Reference Department, Colindale, London (Tel: 0208 327 6204 or out of hours 020 8200 4400).
- In Wales, the duty virologist, University Hospital of Wales, Cardiff (029 20 747 747).
- In Scotland, the local infectious diseases consultant (see the Green Book).
- In Northern Ireland, the regional virology service or the Public Health Agency Duty Room (see the Green Book.)
Immediate action at the time
- Clean the wound with soap or detergent under running tap water for several minutes. Then treat with a suitable disinfectant (eg, 40-70% alcohol, povidone iodine). Prompt wound care significantly reduces the risk of developing rabies.
- Primary suturing of the wound should be avoided or postponed.
- Information gathering for risk assessment:
- Animal involved - species, state of health, vaccination status, name and address of the animal's owner where possible to allow follow-up. This may require enlistment of help from local officials.
- Type and site of injury.
- Country where bite occurred. Local medical advice may be helpful. They are likely to know the level of risk locally and be able to advise on the need for vaccination.
- Date of exposure. As the incubation period for rabies can be prolonged, treatment should still be considered even if the interval from exposure is lengthy.
- Vaccination history of individual exposed.
Post-exposure prophylaxis following risk assessment
The following is a summary of the full algorithm which is available on the PHE website, which also contains the logistics of obtaining HRIG and vaccines, and advice on finishing post-exposure treatment courses which were initiated abroad.
Rabies exposure risk
Unimmunised or not completely immunised
|None||No immunisation||No further immunisation|
|Low||5 doses of rabies vaccine on days 0, 3, 7, 14 and 28-30||2 doses on days 0 and 3-7|
|High||5 doses of rabies vaccine on days 0, 3, 7, 14 and 28-30|
PLUS human rabies-specific immunoglobulin (HRIG) on day 0 only
|2 doses on days 0 and 3-7|
- Rabies vaccine may cause local reactions such as redness, swelling or pain at the site of injection within 24-48 hours of administration.
- Systemic reactions, such as headache, fever, muscle aches, vomiting and urticarial rashes, are rare.
- Reactions may become more severe with repeated doses.
- HRIG may cause local pain and low-grade fever but no serious adverse reactions have been reported.
- Pre-exposure rabies vaccine should not be given to those who have had:
- A confirmed anaphylactic reaction to a previous dose of rabies vaccine.
- A confirmed anaphylactic reaction to any component of the vaccine.
- There are no absolute contra-indications to post-exposure rabies vaccine:
- In the event of a hypersensitivity reaction to a dose of a pre-exposure course, these patients should still receive post-exposure vaccination if indicated, because the risks of rabies outweigh the risks of hypersensitivity.
- When a hypersensitivity reaction occurs during post-exposure immunisation, further doses should be given under close medical supervision.
- Pregnant women and breast-feeding mothers should only be given pre-exposure vaccination if the risk of exposure to rabies is high and rapid access to post-exposure prophylaxis would be limited.
- Post-exposure treatment should be given to pregnant women when indicated.
- Individuals with immunosuppression and HIV infection (regardless of CD4 count) should be given rabies vaccines in accordance with the recommendations above. Antibody response may be inadequate. If exposed to rabies, individuals who are immunosuppressed or who have HIV may require a different regime for post-exposure management. Specialist advice should then be sought urgently.
- Rabies Vaccine BP is available from Sanofi Pasteur MSD (Tel: 0800 085 5511).
- Rabipur® is available from Novartis Vaccines (Tel: 08457 451500) or MASTA (Tel: 0113 238 7500).
- Pre-exposure vaccination in England and Wales for individuals at high occupational risk is supplied by the Department of Health, and should be obtained from PHE Virus Reference Department in Colindale. For others it is obtained from pharmacies via private prescription.
- For post-exposure vaccine and HRIG in England, supplies are available from Colindale on completion of a risk assessment form which acts as a prescription. For advice on supply in Scotland, Wales and Northern Ireland, see the contact details in the post-exposure recommendations section above. For post-exposure prophylaxis, vaccine and HRIG are available free of charge in the NHS.
Further reading and references
Rabies; World Health Organization
Neilson AA, Mayer CA; Rabies - prevention in travellers. Aust Fam Physician. 2010 Sep39(9):641-5.
Crowcroft NS, Thampi N; The prevention and management of rabies. BMJ. 2015 Jan 14350:g7827. doi: 10.1136/bmj.g7827.
Rabies: the green book, chapter 27; Public Health England (April 2013)
BVA advice: rabies vaccination of practice staff; British Veterinary Association, Nov 2013
Travel Health Pro; National Travel Health Network and Centre (NaTHNaC)
Rabies: risk assessment, post-exposure treatment, management; Public Health England
Gautret P, Parola P; Rabies vaccination for international travelers. Vaccine. 2012 Jan 530(2):126-33. Epub 2011 Nov 12.
Request Form for Rabies Post-exposure Treatment; Public Health England