Rabies vaccination

What is rabies?¹

Rabies is an acute viral encephalomyelitis caused by members of the lyssavirus genus. Rabies-related lyssaviruses implicated in human disease include European bat lyssaviruses (EBLVs) and Australian bat lyssavirus (ABLV).

Infection is usually via the bite or scratch of a rabid animal, most frequently a dog. In some parts of the world, other animals are important sources of exposure. In parts of Europe (including the UK) EBLV-1 and EBLV-2 are found in insectivorous bats and have occasionally caused human disease. On rare occasions, transmission of the virus has occurred through body fluids from an infectious animal coming into contact with an individual’s mucous membranes.

The incubation period is generally between 3 and 12 weeks, but may range from 4 days to 19 years. In more than 93% of patients, the onset is within one year of exposure.

The onset of illness is insidious. Early symptoms may include paraesthesiae around the site of the wound, fever, headache and malaise. The disease may then present with hydrophobia, hallucinations and maniacal behaviour progressing to paralysis and coma, or as an ascending flaccid paralysis and sensory disturbance. Rabies is almost always fatal, death resulting from respiratory paralysis.

There is no specific treatment other than supportive care once clinical symptoms develop.

Effective immunisation is available and schedules have been developed for pre-exposure and post-exposure prophylaxis.

How common is rabies? (Epidemiology)¹

Rabies in animals occurs in all continents except Antarctica, although individual countries and islands are reported to be rabies-free. Most countries that are declared rabies-free probably have rabies-related viruses in their bat populations.

• In the US, classical rabies virus in animals has become more prevalent since the 1950s; skunks, raccoons and bats account for 85% of animal cases.

• In Asia, Africa, Central and South America, classical rabies virus (genotype 1) is endemic in feral dogs and is also present in domestic dogs.

• In Mexico and Central and South America, vampire bats carry the classical rabies virus.

Worldwide an estimated 59,000 people die of rabies each year, with the majority of deaths occurring in Asia (59.6%) and Africa (36.4%).

In the UK, deaths from classical rabies continue to occur in people infected abroad. However, only 26 deaths have been reported since 1946, 6 of which have occurred since 2000 and the most recent was in 2018. None had received timely and appropriate post-exposure treatment.

Pre-COVID-19, approximately 2000 people each year required post- exposure treatment in England, of which 12% were potentially exposed to bats in the UK and 88% were potentially exposed to an animal overseas.

No case of indigenous human rabies from animals other than bats has been reported in the UK since 1902. In 2002, a man died from rabies caused by EBLV-2 acquired in the UK from a bat. Only 3 other human cases of EBLV infection (all fatal) have been reported in the past 30 years in Europe.

Rabies vaccine¹

Currently cell-culture derived vaccines are used. There is only one licensed for intramuscular use in the UK: Purified chick embryo cell (PCEC) rabies vaccine, or Rabipur®. The vaccine is inactivated, does not contain live organism and cannot cause rabies.

• For primary pre-exposure immunisation, 3 doses of rabies vaccine (2.5 IU; one vial) should be given intramuscularly on days 0, 7 and 28. The third dose can be given from day 21 if there is insufficient time before travel.

• An accelerated course of primary pre-exposure immunisation may be given if there is insufficient time before travel to complete the 21-28 day course. Three doses of rabies vaccine (2.5IU) should be given intramuscularly on days 0, 3 and 7, with an additional dose at one year if they will continue to travel to high risk (enzootic) areas.

• For post-exposure treatment schedules, the doses required will depend on a risk assessment and the calculation of a Composite Rabies Risk (CRR).

Other WHO approved cell culture-derived vaccines are available in other countries and may contain different concentrations of rabies antigen.

Rabies specific immunoglobulin¹

Human rabies immunoglobulin (HRIG) is obtained from the plasma of immunised and screened human donors. HRIG is used after high risk exposure to rabies to give rapid protection by neutralising the rabies virus at the wound site until rabies vaccine, which should be given at a separate site at the same time, becomes effective.

When indicated for post-exposure treatment, HRIG at a dose of 20 IU/kg body weight should be infiltrated in and around the cleansed wound. HRIG is of greatest value when infiltrated at the wound site as it neutralises rabies virus at the wound site before the immune system can respond to the vaccine by producing antibodies. The benefit of intramuscular administration of HRIG away from the site of the wound is likely to be negligible.

If vaccine is given but HRIG treatment is delayed, HRIG can still be given up to seven days after starting the course of vaccine. HRIG is no longer required once an active antibody response to the rabies vaccine has started to develop. Therefore, HRIG is not indicated more than seven days after the first dose of vaccine, or more than one day after the second dose of vaccine.

Recommendations: pre-exposure prophylaxis¹

In the UK, pre-exposure (prophylactic) immunisation is recommended for:

• Laboratory staff routinely working with rabies virus.

• Workers at DEFRA-authorised quarantine premises and carriers.

• Those who regularly handle bats, including on a voluntary basis, in the UK.

• Veterinary and technical staff who, by reason of their employment, encounter enhanced risk.

• Those travelling outside the UK:

  • Animal control and wildlife workers, veterinary staff or zoologists who regularly work in rabies enzootic areas.

  • Travellers to rabies enzootic areas, especially if:

    • Post-exposure medical care and rabies biologics at the destination are lacking or in short supply.

    • They are undertaking higher risk activities such as cycling or running.

    • They are living or staying for more than one month.

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.²

Recommendations: post-exposure management¹

Post-exposure management normally consists of wound treatment and risk assessment for appropriate post-exposure treatment.

Treatment and immunisation after a possible rabies exposure will depend on the circumstances of the exposure, including the nature of the exposure, the species involved, the country/area and the immune status of the exposed person.

Detailed guidance on risk assessment and management of potential rabies exposure can be found on the UK Health Security Agency (UKHSA) and Health Protection Scotland websites (see 'Further Reading' below).

Adverse reactions¹

• 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.

Contra-indications¹

• 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.

Supplies of vaccine¹

Rabipur® is available from Valneva UK (Tel: 01252 762208) or MASTA (Tel: 0113 238 7500).

Employers have a responsibility to assess the risks for exposure to hazardous agents, including rabies virus, and to protect employees from those risks as is reasonably practicable. This includes the provision of pre-exposure rabies immunisation if indicated.

In England, rabies vaccine for pre-exposure immunisation will only be provided by UK Health Security Agency for bat handlers where no formal employer can be identified. This can be obtained from the Rabies and Immunoglobulin Service (rigs.ig.clerks@nhs.net) using the dedicated form (https://www.gov.uk/government/publications/rabies-pre-exposure-request-form).

For other pre-exposure indications, it can be obtained through local pharmacies by private prescription. UKHSA does not supply pre-exposure rabies immunisation for travellers.

Rabies vaccine and HRIG for use in post-exposure treatment are available free of charge to patients and providers from UKHSA. To facilitate prompt access for patients, NHS services are expected to arrange local seven-day access to a small number of doses of rabies vaccine to initiate a course. Any vaccine held locally that is used for post-exposure treatment will be replaced free of charge by UKHSA. Information may be obtained from the local health
protection team (https://www.gov.uk/health-protection-team) or UKHSA Rabies and Immunoglobulin Service (Tel 0330 128 1020) or out of hours via the UKHSA Colindale Duty Doctor (Tel: 020 8200 4400).

In Northern Ireland, rabies vaccine for post-exposure treatment is available from the Royal Victoria Hospital Pharmacy Department, BHSCT (Tel: 028 9024 0503) and HRIG from the Northern Ireland Blood Transfusion Service (Tel: 077 7461 9337, Duty Biomedical Scientist). Advice on risk assessment is available from the PHA Duty Room (Tel: 030 0555 0119), if required.

In Scotland, post-exposure treatment is available through local on-call infectious disease consultant/infection specialist or public health team.

In Wales, post-exposure treatment is provided through the Public Health Wales All Wales Acute Response Service (AWARe) (Tel: 030 0003 0032).