Introduction

Rabies is a fatal viral infection, is usually acquired in humans from the bite of an infected animal. Nearly all deaths in humans worldwide result from the bite of a rabid dog.¹

Between 2000-2005 there were 4 cases of rabies in the UK,² 3 acquired from dog bites abroad (Philippines, India and Nigeria) and 1 from the bite of an infected UK bat (2002).³

Active and passive immunisation is available and schedules have been developed for pre-exposure and post-exposure prophylaxis. There is no treatment for rabies.

Rabies vaccine

• Currently cell-culture derived vaccines are used. There are 2 licensed for use in the UK:
  • Human diploid cell vaccine (HDCV), or Rabies Vaccine BP Sanofi Pasteur Verorab®.
  • Purified chick embryo cell (PCEC) rabies vaccine, or Rabipur®.
  They are freeze-dried, inactivated and contain traces of neomycin. They should be stored at 2-8 degrees Celsius and discarded if unused 1 hour after reconstitution. Administration is usually deep subcutaneous or intramuscular, in the deltoid region. They can be used interchangeably.
• New, more potent DNA vaccines are being developed.⁴
• Rabies-specific immunoglobulin is available - human rabies immune globulin (HRIG) - and is derived from the plasma of immunised human donors for passive immunisation.
• Other cell-culture derived vaccines are available in other countries but these are no longer recommended.

Recommendations: pre-exposure prophylaxis

At-risk groups

This is available free on the NHS to:

• Laboratory workers handling the virus.
• Workers handling imported animals.
• Licensed bat handlers.
• Workers in at-risk jobs, in at-risk areas.
• Health workers likely to have contact with infected patients.

It is also recommended, but not free on the NHS, to:

• Travellers to high-risk areas for stays of more than one month where there is also limited access to medical care and particularly to easy post-exposure prophylaxis. Up-to-date information on other countries to assess - this can be found on the NaTHNaC website - see the link below.
• Travellers to high-risk areas for stays of less than one month who may be exposed to rabies because of their travel activities and limited access to post-exposure medical care.

Routes of administration and dosage schedules

The options are:

• Primary, pre-exposure protection: give 3 doses, 1 ml deep subcutaneous/intramuscular deltoid region at days 0, 7 and 28. (0, 7, 21 or 28 with Rabipur®).
• Unlicensed intradermal route for rapid immunisation (e.g. nursing an infected patient): 0.1 ml intradermally each limb (0.4 mls total).⁵

Reinforcing doses

In the UK, not necessary unless:

• Risk regular and continuous and post-exposure treatment difficult: 2 to 3-yearly reinforcing dose.
• Those working with the live virus: serological testing advised 6-monthly.

Recommendations: post-exposure prophylaxis

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 the Health Protection Agency Virus Reference Department, Colindale, London on 020 8200 4400 or the Communicable Disease Surveillance Centre on 020 8200 6868.

Immediate action at the time

1. Clean the wound with soap under running tap water for 5 minutes. Then treat with 70% alcohol solution or topical iodine solution.⁶
2. Information gathering: name and address of the animal's owner to allow follow-up. This may require enlistment of help from local officials.
3. Local medical advice should be sought. They are likely to know the level of risk locally and be able to advise on the need for vaccination.

Rabies specific immunoglobulin (HRG)

• HRG (passive immunisation) is used after exposure to rabies for rapid protection until the rabies vaccine (active immunisation) becomes effective.
• It is given at the same time but at a separate site as part of post-exposure prophylaxis.
• The dose is HRG 20 IU/kg body weight. It is administered around the cleansed wound or intramuscularly (anterolateral thigh) if the wound has healed or is not visible.
• It can be given for up to 7 days after starting the vaccination course (active immunisation).

Action on return to this country

1. Wound care, as above.
2. Information about the biting animal following up on above information.
3. Information about the level of risk in the country, using the numbers above.

Summary

Adverse reactions

These are generally minor including local reactions within 24-48 hours but may be more of a problem with repeated doses of the vaccine. Systemic reactions have been reported, as has anaphylaxis. Local reactions with HRG have been reported.

Contra-indications

Hypersensitivity to the vaccine or acute febrile illness are contra-indications for pre-exposure prophylaxis.⁶ In pregnancy, vaccine should only be given if the level of risk is high for pre-exposure prophylaxis.

Supplies of vaccine

• Human diploid cell vaccine (HDCV) from Sanofi Pasteur (Tel 01628 773200).
• HDCV for pre-exposure with occupational risk via PHLS 020 8200 4400 and for others/travellers from local pharmacies with private prescription.
• Post-exposure-centres in the PHLS Directory - also advise re HRG availability.

Document references

1. Meslin FX; Rabies as a traveler's risk, especially in high-endemicity areas. J Travel Med. 2005 Apr;12 Suppl 1:S30-40. [abstract]
2. Johnson N, Brookes SM, Fooks AR, et al; Review of human rabies cases in the UK and in Germany. Vet Rec. 2005 Nov 26;157(22):715.
3. Fooks AR, McElhinney LM, Pounder DJ, et al; Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med Virol. 2003 Oct;71(2):281-9. [abstract]
4. Bahloul C, Taieb D, Diouani MF, et al; Field trials of a very potent rabies DNA vaccine which induced long lasting virus neutralizing antibodies and protection in dogs in experimental conditions. Vaccine. 2006 Feb 20;24(8):1063-72. Epub 2005 Sep 21. [abstract]
5. Immunisation against infectious disease - 'The Green Book', Dept of Health (various dates)
6. Summary of Product Characteristics - Rabies Vaccine BP; Sanofi Pasteur MSD, Updated Oct 2007, electronic Medicines Compendium

Internet and further reading

• Immunisation against infectious disease - 'The Green Book', Dept of Health (various dates)
• No authors listed; Meeting of the Immunization Strategic Advisory Group of Experts, November 2007--conclusions and recommendations. Wkly Epidemiol Rec. 2008 Jan 4;83(1):1-15.
• No authors listed; Rabies vaccines. WHO position paper. Wkly Epidemiol Rec. 2007 Dec 7;82(49-50):425-35.
• National Travel Health Network and Centre
• Gompf SG; Rabies, eMedicine, Oct 2008.

Acknowledgements