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    Cause Transmission
    Rabies is a zoonotic disease affecting a wide range of domestic and wild mammals, including bats. The virus is present primarily in the saliva and infection of humans usually occurs through the bite of an infected animal, usually a dog, which may not show signs of rabies.Transmission may occasionally occur also through other contact with a rabid animal, for example following a penetrating scratch with bleeding, or through licking of broken skin and mucosa. Laboratoryconfirmed person-to-person transmission other than via organ transplant has not been reported.

    Cause Nature of the disease

    Rabies is 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 abnormal fear of drafts of air (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 paralysis and loss of sensation, weakness and pain.

    Cause Geographical distribution
    Rabies is present in mammals in most parts of the world (see map). Most of the estimated 55 000 human rabies deaths per year occur in Africa and Asia. More information on rabies is available at www.who.int/rabies/rabnet/en.

    Cause Risk for travellers 

    The risk to travellers in areas where rabies occurs (see map, or http://www.who.int/rabies/rabnet/en) is proportional to the probability of contact with potentially rabid mammals. In most developing countries, the estimated ratio of dogs, both owned and ownerless, to humans is 1:10 and an average 100 suspected rabid dog bites per 100 000 inhabitants are reported annually. As rabies is a lethal disease, medical advice should be sought immediately at a competent medical centre – ideally, 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, free-ranging or 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.

    The map shows the WHO categories of risk, from no-risk (rabies- free) countries or areas to countries or areas of low, medium and high risk (dog rabies). Categorization is based primarily on the animal host species in which the rabies virus is maintained, e.g. bats and/or other wildlife and/or dogs, and on the availability of reliable laboratory-based surveillance data from these reservoir species. 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 (see below), 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, (e.g., 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. Prophylaxis 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 through playing with animals, particularly with dogs and cats; they may receive more severe bites and are less likely to report contact with suspect rabies animals.

    Cause 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 the development of clinical rabies after exposure has occurred, usually following the bite of an animal suspected of having rabies, i.e. post-exposure prophylaxis.

    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 officers, and other individuals living in or travelling to countries or areas at risk. 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 countries or areas at risk, where they provide an easy target for rabid animals. Pre-exposure vaccination is also recommended for individuals travelling to isolated areas or to areas where immediate access to appropriate medical care is limited or to countries where modern rabies vaccines are in short supply and locally available rabies vaccines might be unsafe and/or ineffective.

    Pre-exposure rabies vaccination consists of three full intramuscular (i.m.) doses of cell-culture- or embryonated-egg-based 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 1 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 (i.d.) 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 qualified medical supervision. 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.

    Periodic booster injections are 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, individuals 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 first 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 patients who have previously received a complete vaccination series.

    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 intramuscular or intradermal injections.

    For information on which vaccines are recommended for intradermal use, see: www.who.int/rabies/human/postexp/en/index.html. In the event of exposure through the bite or scratch of an animal known or suspected to be rabid, individuals who have previously received a complete series of pre-exposure or post-exposure cell-culture- or embryonated egg- rabies vaccine should receive two booster doses of vaccine, the first dose ideally on the day of exposure and the second 3 days later. Rabies immunoglobulin should not be administered.

    Post-exposure prophylaxis
    In countries or areas at risk of rabies, the circumstances of an animal bite or other contact with an animal suspected to be rabid may require post-exposure prophylaxis. In such situations, medical advice should be obtained immediately. Strict adherence to the WHO-recommended guidelines for optimal post-exposure rabies prophylaxis virtually guarantees protection from the disease. The administration of vaccine, and immunoglobulin if required, must be conducted by, or under the direct supervision of, a physician. Post-exposure prophylaxis depends on the type of contact with the confirmed or suspect rabid animal, as follows:

    Exposure to rodents, rabbits and hares seldom, if ever, requires specific anti-rabies post exposure prophylaxis. If an apparently healthy dog or cat in or from a low-risk country or area is placed under observation, the situation may warrant delaying initiation of treatment. This observation period applies only to dogs and cats. Except in the case of threatened or endangered species, other omestic and wild animals suspected to be rabid should be humanely killed and their tissues examined for the presence of rabies antigen using appropriate laboratory techniques. Post-exposure prophylaxis should be considered for individuals who have been in close contact with bats, particularly following bites or scratches or exposure to mucous membranes.

    1. Wound treatment
    Thorough washing of the wound with soap/detergent and water, followed by the application of ethanol or an aqueous solution of iodine or povidone.

    2. Passive immunization
    Human rabies immunoglobulin (HRIG) or equine rabies immunoglobulin (ERIG) or F(ab’)2 products should be used for category III exposures as well as for some category II exposures (see table, above). Passive immunization should be administered just before or shortly after administration of the first dose of vaccine given in the post-exposure prophylaxis regimen. If it is not immediately available, passive immunization can be administered up until the seventh day after initiation of the primary series of post exposure prophylaxis (with cell-culture or embryonated-egg rabies vaccine). Dosage and administration: The dose for HRIG is 20 IU/kg body weight and for ERIG and F(ab’)2 products 40 IU/kg body weight. The full dose of rabies immunoglobulin, or as much as is anatomically feasible, should be administered into and around the wound site. Any remainder should be injected i.m. at a site distant from the site of active vaccine administration. Multiple needle injections into the wound should be avoided. If the correct dose of rabies immunoglobulin is too small to infiltrate all wounds, as might be true of a severely bitten individual, it can be diluted in physiological buffered saline to ensure greater wound coverage.

    3. Active immunization
    Cell-culture- or embryonated-egg-based rabies vaccines should always be used for post-exposure prophylaxis. They can be administered either i.m. or i.d. Intramuscular regimens: Both a five-dose and a four-dose i.m. regimen are recommended for post-exposure vaccination; the five dose regimen is the more commonly used:
    • The five-dose regimen is administered on days 0, 3, 7, 14 and 28 into the deltoid muscle.
    • The four-dose regimen is administered as two doses on day 0 (one dose in the right and one in the left arm (deltoid muscles), and then one dose on each of days 7 and 21 into the deltoid muscle.
    An alternative post-exposure regimen for healthy, fully immuno competent exposed people who receive wound care plus high-quality rabies immunoglobulin plus WHO-prequalified rabies vaccines consists of four doses administered i.m. on days 0, 3, 7 and 14.
    Intradermal regimens: Intradermal administration of cell-culture- and embryonated-egg-based rabies vaccines has been successfully used in many developing countries that cannot afford the five- or four-dose i.m. schedules.
    • The two-site i.d. method: one i.d. injection at two sites on days 0, 3, 7 and 28.
    The volume per intradermal injection should be 0.1 ml with both purified Vero cell rabies vaccine, and purified chick embryo rabies vaccine.

    Information source: http://www.who.int/ith/chapters/en/