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Rabies post-exposure prophylaxis
In a rabies-endemic area, 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.

Post-exposure prophylaxis to prevent the establishment of rabies infection involves first-aid treatment of the wound followed by administration of rabies vaccine; in the case of category III exposure, rabies immunoglobulin should also be administered.

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:

Category	Type of contact with a suspect or confirmed rabid Domestic or wild* animal, or Animal, or Animal unvailable for testing	Type of exposure	Recomended post exposure prophylaxis
1	Touching or feeding of animals Licks on intact ski	None	None,if reliable case history is available
2	Nibbling of uncovered skin Minor scrathes or abrasions without bleeding	Minor	Administer vaccine immediately Stop treatment if animal remains Healthy throughout an Observation period of 10 Days* or is proved to be Negative for rabies by a Reliable laboratory using Appropriate diagnostic Techniques.
3	Single or multiple trasdermal bites or scrathes licks on broken skin Contamination of mucous membrane with saliva (i.e licks) Exposure to bats****	Servere	Administer vaccine immediately Stop treatment if animal remains Healthy throughout an Observation period of 10 days* or is proved to be negative for rabies by aReliable laboratory using appropriate diagnostic Techniques

* 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 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 domestic and wild animals suspected to be rabid should be killed and their tissues examined for the presence of rabies antigen using appropriate laboratory techniques.
**** Post-exposure prophylaxis should be considered when contact between a human and a bat has occurred unless the exposed person can rule out a bite or scratch or exposure to a mucous membrane.

(1) Local treatment of wounds (first aid treatment)
Elimination of the rabies virus at the site of bite or scratch by chemical or physical means is an effective mechanism to aid in the protection against infection. Immediate washing and flushing for a minimum of 15 minutes with soap or detergent and water, or water alone, is imperative. Following washing, ethanol (70%) or iodine or povidone iodine should be applied. Most severe bite wounds are best treated by daily dressing. Suturing should be avoided; if it cannot be avoided, the wound should first be infiltrated with passive rabies immunization products and suturing delayed for several hours. This will allow diffusion of the antibody through the tissues before suturing is performed. Antibiotics and tetanus prophylaxis should be administered as appropriate for other wounds.

(2) Rabies biologicals for passive immunization:
Rabies immunoglobulins (RIG) should be administered in all category III exposures (as well as in category II exposures when the patient is immunosuppressed). Human rabies immunglobulin (HRIG) is mainly available in industrialized countries; both purified equine rabies immunoglobulin (ERIG) and human immunoglobulin are used in developing countries. F(ab’)2 products have recently been developed from equine immunoglobulins. Given that the clearance of F(ab’)2 fragments is more rapid than that of intact immunoglobulins, in case of multiple severe exposures, HRIG should preferably be used for passive immunization.

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 vaccine administration. Multiple needle injections into the wound should be avoided. If the dose of rabies immunoglobulin is too small to infiltrate all wounds, as might be true of a severely bitten individual, the correct dosage of rabies immunoglobulin can be diluted in physiological buffered saline to ensure greater wound coverage.

HRIG gives rise to virtually no serious adverse reactions. ERIG is now highly purified and the occurrence of adverse events has been significantly reduced (<1–2%>, compared with 40% for the original unpurified rabies antisera). F(ab’)2 products were originally developed from equine immunoglobulins in order to reduce the severe adverse reactions initially described in association with the use of heterologous immunoglobulin products. Thus, they cause virtually no serious adverse reactions. Pregnancy, infancy, old age and concurrent illness are not contraindications for rabies post-exposure prophylaxis in the event of an exposure.

Rabies biologicals for passive immunization should not be administered later than 7 days after post-exposure vaccination with cell-culture or embryonated egg rabies vaccine has been initiated.

(3) Active immunization for post-exposure prophylaxis:
Highly purified and potent modern cell-culture or embryonated egg vaccines should be used. Cell-culture and embryonated egg vaccines can be administered either inttramuscular or intradermal. Two i.m. regimens are recommended for post-exposure vaccination; the five-dose regimen (Essen regimen) is the more commonly used:

1) Essen regimen: this five-dose regimen is administered on days 0, 3, 7, 14 and 28 in the deltoid muscle.
2) Zagreb or ‘2-1-1’ regimen: administered as 2 doses on day 0 (one dose in the right and one in the left deltoid), and one dose on each of days 7 and 21 in the deltoid muscle. Intradermal regimens:

Intradermal administration of cell-culture and embryonated egg rabies vaccines has been successfully used in many developing countries that cannot afford the five-dose intramuscular schedule. Intradermal schedules have been evaluated and used extensively for post-exposure prophylaxis in some developing countries to replace nerve–tissue vaccines where intramuscular vaccination regimens are not an alternative from an economic viewpoint. Intradermal injections should be administered by staff well trained in the technique. WHO recommends the following intradermal regimens and vaccines for use by the intradermal route:

8-site intradermal method (8-0-4-0-1-1): one intradermal injection at 8 sites on day 0 (one in each upper arm, one in each lateral thigh, one on each side of the suprascapular region, and one on each side of the lower quadrant region of the abdomen); one injection at 4 sites on day 7 (one in each upper arm and in lateral thigh); and one injection at one site on days 30 and 90 (one upper arm). For use with: human diploid cell vaccine (HDCV) and purified chick embryo cell vaccine (PCECV).
2-site intradermal method (2-2-2-0-2): one intradermal injection at 2 sites on days 0, 3, 7 and 28.

Both vaccines at 0.1 ml per intradermal site.

Post-exposure rabies prophylaxis
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 immunglobulin or equine rabies immunglobulin or F(ab’)2 products for category III exposure (see table, above). Human rabies immunoglobulin should be used in case of multiple severe exposure. Passive immunization should be administrered just before 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 the primary series of post-exposure prophylaxis (with cell-culture or embryonated egg rabies vaccine) was initiated.

3. Active immunization: Cell-culture or embryonated egg rabies vaccines should always be used for post-exposure prophylaxis (see regimens above)*.

Post-exposure prophylaxis in previously vaccinated individuals: For persons who have previously received a full course of cell-culture or embryonated egg rabies vaccine, post-exposure prophylaxis consists of a series of two booster doses of vaccine given either intramuscularly or intradermally on days 0 and 3. It is not necessary to administer passive immunization products.

* Post-exposure prophylaxis can be stopped if the suspect animal is proved by appropriate laboratory examination to be free of rabies or, in the case of domestic dogs and cats, if the animal remains healthy throughout a 10-day observation period.

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