Cause
The rabies virus, a rhabdovirus of the genus Lyssavirus.
Transmission
Rabies is a zoonotic disease affecting a wide range of domestic and wild mammals, including bats. Infection of humans usually occurs through the bite of an infected animal as the virus is present in the saliva. Any other contact with a rabies-susceptible species such as a penetrating scratch with bleeding and licking of broken skin and mucosa in an area where rabies is present should be treated with caution. In developing countries, transmission is usually through dog bites. Person-to-person transmission has not been laboratory-confirmed.
Nature of the disease
An acute viral encephalomyelitis, which is almost invariably fatal. The initial signs include a sense of apprehension, headache, fever, malaise and sensory changes around the site of the animal bite. Excitability, hallucinations and aerophobia are common, followed in some cases by fear of water (hydrophobia) due to spasms of the swallowing muscles, progressing to delirium, convulsions and death a few days after onset. A less common form, paralytic rabies, is characterized by loss of sensation, weakness, pain and paralysis.
Geographical distribution
Rabies is present in mammals in many countries worldwide (see Map). Most of the estimated 55 000 rabies deaths per year in Africa and Asia alone occur in developing countries and follow a dog bite.
Risk for travellers
The risk to travellers in areas endemic for rabies is proportional to their contact with potentially rabid mammals. Dogs, both owned and ownerless, are very common, with an estimated 1:10 ratio of dogs to humans in most developing countries. An average of 100 suspected rabid dog bites per 100 000 inhabitants are reported in endemic countries. According to a recent survey conducted in India, 1.6% of the total population received a dog bite during a 12-month period. As rabies is a lethal disease, medical advice should be sought immediately at a competent medical centre, ideally in the rabies treatment centre of a major city hospital. First-aid measures should also be started immediately (see Post-exposure prophylaxis, below).
Travellers should avoid contact with free-roaming animals, especially dogs and cats, and with wild and captive animals. For travellers who participate in caving or spelunking, casual exposure to cave air is not a concern, but cavers should be warned not to handle bats. In most countries of the world, suspect contact with bats should be followed by post-exposure prophylaxis.
WHO defines 4 risk categories: from no risk (rabies-free areas), to low, medium and high risk (areas with endemic dog rabies). Categorization is based primarily on the animal host species in which rabies virus(es) is/are maintained in a country, that is bats and/or other wildlife and/or dogs. Access to proper medical care and the availability of modern rabies vaccines have also been taken into consideration on a country basis. In countries belonging to categories 2–4, pre-exposure immunization against rabies is recommended for travellers with certain characteristics:
- Category 1: no risk.
- Category 2: low risk. In these countries travellers involved in activities that might bring them into direct contact with bats (for example, wildlife professionals, researchers, veterinarians and adventure travellers visiting areas where bats are commonly found) should receive pre-exposure prophylaxis.
- Category 3: medium risk. In these countries, travellers involved in any activities that might bring them into direct contact with bats and other wild animals especially carnivores (for example, wildlife professionals, researchers, veterinarians and travellers visiting areas were bats and wildlife are commonly found) should receive pre-exposure prophylaxis.
- Category 4: high risk. In these countries, travellers spending a lot of time in rural areas involved in activities such as running, bicycling, camping, or hiking should receive pre-exposure prophylaxis. It is also recommended for people with significant occupational risks, such as veterinarians, and expatriates living in areas with a significant risk of exposure to domestic animals, particularly dogs, and wild carnivores. Children should be immunized as they are at higher risk due to playing with animals, particularly with dogs and cats, may receive more severe bites or are more likely not to report contact with suspect rabies animals.
Vaccine
Vaccination against rabies is used in two distinct situations:
– to protect those who are at risk of exposure to rabies, i.e. pre-exposure vaccination;
– to prevent clinical rabies occurrence after exposure has occurred, usually following the bite of an animal suspected of having rabies, i.e. post-exposure prophylaxis.
The vaccines used for pre-exposure and post-exposure vaccination are the same, but the immunization schedule differs according to the type of application. Rabies immunoglobulin is used only for post-exposure prophylaxis. Modern vaccines of cell-culture or embryonated egg origin are safer and more effective than the older vaccines, which were produced in brain tissue. These modern rabies vaccines are now available in major urban centres of most countries of the developing world. Rabies immunoglobulin, on the other hand, is in short supply worldwide and may not be available even in major urban centres in many dog rabies-infected countries.
Pre-exposure vaccination
Pre-exposure vaccination should be offered to people at high risk of exposure to rabies, such as laboratory staff working with rabies virus, veterinarians, animal handlers and wildlife offi cers, and other individuals living in or travelling to areas where rabies is endemic. Travellers with extensive outdoor exposure in rural areas – such as might occur while running, bicycling, hiking, camping, backpacking, etc. – may be at risk, even if the duration of travel is short. Pre-exposure vaccination is advisable for children living in or visiting rabies-endemic areas, where they provide an easy target for rabid animals. Pre-exposure vaccination is also recommended for persons travelling to isolated areas or to areas where immediate access to appropriate medical care is limited or to countries where biologicals are in short supply and locally available rabies vaccines might be unsafe and/or ineffective.
Pre-exposure vaccination consists of three full intramuscular doses of cell-culture or embryonated egg origin rabies vaccine given on days 0, 7 and 21 or 28 (a few days’ variation in the timing is not important). For adults, the vaccine should always be administered in the deltoid area of the arm; for young children (under 2 years of age), the anterolateral area of the thigh is recommended. Rabies vaccine should never be administered in the gluteal area: administration in this manner will result in lower neutralizing antibody titres.
To reduce the cost of cell-derived vaccines for pre-exposure rabies vaccination, intradermal vaccination in 0.1-ml volumes on days 0, 7 and either 21 or 28 may be considered. This method of administration is an acceptable alternative to the standard intramuscular administration, but it is technically more demanding and requires appropriate staff training and qualifi ed medical supervision. As an open vial should not be kept for more than 6 hours, wastage can be avoided by vaccinating several people during that period. Concurrent use of chloroquine can reduce the antibody response to intradermal application of cell-culture rabies vaccines. People who are currently receiving malaria prophylaxis or who are unable to complete the entire three-dose pre-exposure series before starting malarial prophylaxis should therefore receive pre-exposure vaccination by the intramuscular route.
Rabies vaccines will induce long-lasting memory cells, giving rise to an accelerated immune response when a booster dose of vaccine is administered. Periodic booster injections are therefore not recommended for general travellers. However, in the event of exposure through the bite or scratch of an animal known or suspected to be rabid, persons who have previously received a complete series of pre- or post-exposure rabies vaccine (with cell-culture or embryonated egg vaccine) should receive two booster doses of vaccine. Ideally, the fi rst dose should be administered on the day of exposure and the second 3 days later. This should be combined with thorough wound treatment (see Post-exposure prophylaxis, below). Rabies immunoglobulin is not required for previously vaccinated patients (as mentioned above).
Periodic booster injections are recommended only for people whose occupations put them at continuous or frequent risk of rabies exposure, e.g. rabies researchers or staff in diagnostic laboratories where rabies virus is present.
For persons at continuous or frequent risk of rabies exposure who have previously received pre-exposure rabies vaccination, a booster vaccination is administered if the serological titre of the person at risk falls below 0.5 IU/ml, the antibody level considered to be protective.
Precautions and contraindications
Modern rabies vaccines are well tolerated. The frequency of minor adverse reactions (local pain, erythema, swelling and pruritus) varies widely from one report to another. Occasional systemic reactions (malaise, generalized aches and headaches) have been noted after both intramuscular and intradermal injections.
Type of vaccine: Modern cell-culture or embryonated egg vaccine
Number of doses: Three, one on each of days 0, 7 and 21 or 28, given i.m. (1 ml/dose) or i.d. (0.1 ml/per inoculation site)
Booster: Not routinely needed for general travellers
Adverse reactions: Minor local or systemic reactions
Before departure: Pre-exposure prophylaxis for those planning a visit to a rabies-endemic country, especially if the visited area is far from major urban centres where appropriate care, including the availability of post-exposure rabies prophylaxis, is not assured.