Rabies Description Rabies is an acute, fatal encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus, almost

always transmitted by an animal bite that innoculates the virus into wounds. Very rarely rabies has been transmitted by nonbite exposures that introduce the virus into open wounds or mucous membranes. The disease progresses from a nonspecific prodromal phase to paresis or paralysis; spasms of swallowing muscles can be stimulated by the sight, sound, or perception of water (hydrophobia); delirium and convulsions can develop, followed by coma and death. All mammals are believed to be susceptible, but reservoirs consist of carnivores and bats. Although dogs are the main reservoir in developing countries, the epidemiology of the disease differs sufficiently from one region or country to another to warrant the medical evaluation of all mammal bites. Occurrence Rabies is found on all continents, except Antarctica. In certain areas of the world, canine rabies remains highly endemic, including (but not limited to) parts of Brazil, Bolivia, Colombia, Ecuador, El Salvador, Guatemala, India, Mexico, Nepal, Peru, the Philippines, Sri Lanka, Thailand, and Vietnam. The disease is also found in dogs in most of the other countries of Africa, Asia, and Central and South America, except as may be noted in Table 3-12. Table 3-12 lists countries that have reported no cases of rabies during the most recent 2-year period for which information is available (formerly referred to as "rabies-free countries"). Additional information can be obtained from the local health authorities of the country, the embassy, or the local consulate's office in the United States. Risk for Travelers Travelers to rabies-endemic countries should be warned about the risk of acquiring rabies, although rabies vaccination is not a requirement for entry into any country. Travelers with extensive unprotected outdoor, evening, and nighttime exposure in rural areas, such as might be experienced while bicycling, camping, or engaging in certain occupational activities, might be at high risk even if their trip is brief. Preventive Measures Vaccine

Preexposure vaccination with human diploid cell rabies vaccine (HDCV), purified chick embryo cell (PCEC) vaccine, or rabies vaccine adsorbed (RVA) may be recommended for international travelers based on the local incidence of rabies in the country to be visited, the availability of appropriate antirabies biologicals, and the intended activity and duration of stay of the traveler. Preexposure vaccination may be recommended for veterinarians, animal handlers, field biologists, spelunkers, missionaries, and certain laboratory workers. Table 3-13 provides criteria for preexposure vaccination. Preexposure vaccination does not eliminate the need for additional medical attention after a rabies exposure, but simplifies postexposure prophylaxis in populations at risk by eliminating the need for rabies immune globulin (RIG) and by decreasing the number of doses of vaccine required. Preexposure vaccination is of particular importance for travelers at risk of exposure to Table 3-12.--Countries and Political Units Reporting No Cases of Rabies During 1997 and 1998.* Region Countries Africa Cape Verde, Libya, Mauritius, Runion, and Seychelles Americas North: Bermuda; St. Pierre and Miquelon Caribbean: Antigua and Barbuda, Aruba, Bahamas, Barbados, Cayman Islands, Guadeloupe, Jamaica, Martinique, Montserrat, Netherlands Antilles (Bonaire, Curaao, Saba, Sint Maarten, and Saint Eustatius), Saint Kitts (Saint Christopher) and Nevis, Saint Lucia, Saint Martin, Saint Vincent and Grenadines, and Virgin Islands (U.K. and U.S.) South: Uruguay Asia Armenia, Bahrain, Brunei, Cyprus, Hong Kong, Japan, Kuwait, Malaysia (Sabah and Sarawak), Maldives, Qatar, Singapore, Taiwan, and United Arab Emirates Europe Albania, Andorra, Faroe Islands, Finland, Gibraltar, Greece, Iceland, Ireland, Isle of Man, Italy, Jersey, Malta, Monaco, Norway (mainland), Portugal, Spain*(except Ceuta/Melilla), Sweden, Switzerland, and United Kingdom Oceania Australia*, Cook Islands, Fiji, French Polynesia, Guam, Kiribati, New Caledonia, New Zealand, Palau, Papua New Guinea, Samoa, and Vanuatu * Bat rabies might exist in some areas that are free of terrestrial rabies. Most of Pacific Oceania is reportedly rabies-free.

rabies in countries where the locally available rabies vaccines might carry a high risk of adverse reactions. Preexposure vaccination can also provide protection when there is an unapparent or unrecognized exposure to rabies and when postexposure prophylaxis might be delayed. Purified equine rabies immune globulin (ERIG) has been used effectively in developing countries where human rabies immune globulin (RIG) might not have been available. If necessary, such heterologous product is preferable to no RIG administration in human rabies postexposure pro-phylaxis. The incidence of adverse reactions after the use of these products has been low (0.8% to 6.0%), and most of those that occurred were minor. However, such products are neither evaluated by U.S. standards nor regulated by the U.S. Food and Drug Administration, and their use cannot be unequivocally recommended at this time. In addition, unpurified antirabies serum of equine origin might still be used in some countries where neither human RIG nor ERIG are available. The use of this antirabies serum is associated with higher rates of serious adverse reactions, including anaphylaxis. Table 3-13.--Criteria for Preexposure Immunization. Risk Category Nature of Risk Typical Populations Preexposure Regimen Continuous Virus present continuously, often in high concentrations. Specific exposures likely to go unrecognized. Bite, nonbite, or aerosol exposure. Rabies research laboratory workers;* rabies biologics production workers. Primary course: Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level. Frequent Exposure usually episodic with source recognized, but exposure might also be unrecognized. Bite, nonbite, or aerosol exposure possible. Rabies diagnostic laboratory workers,* spelunkers, veterinarians and staff, and animal control and wildlife workers in rabies-epizootic areas. Primary course: Serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level. Infrequent (greater than general population) Exposure nearly always episodic with source recognized. Bite or nonbite exposure. Veterinarians, animal control and wildlife workers in areas with low rabies rates; veterinary students; and travelers visiting areas where rabies is enzootic and immediate access to appropriate medical care, including biologics, is limited. Primary course: No serologic testing or booster vaccination. Rare (general population) Exposure always episodic, with source recognized.

Bite or nonbite exposure. U.S. population at large, including individuals in rabiesepizootic areas. No preexposure immunization necessary. * Judgement of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (see U.S. Department of Health and Human Services Biosafety in Microbiological and Biomedical Laboratories, 1984). Preexposure booster immunization consists of one dose of human diploid cell [rabies] vaccine (HDCV), purified chick embryo cell (PCEC) vaccine, or rabies vaccine adsorbed (RVA), 1.0 milliliter (mL) dose, intramuscular (IM) (deltoid area), or HDCV, 0.1 mL intradermal (ID) (deltoid). Minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test. A booster dose should be administered if titer falls below this level.

Table 3-14.--Preexposure Immunization.* Vaccine Dose Number of Doses Schedule (Days) Route HDCV 1.0 ml 3 0, 7, 21 or 28 Intramuscular PCEC 1.0 ml 3 0, 7, 21 or 28 Intramuscular RVA 1.0 ml 3 0, 7, 21 or 28 Intramuscular Abbreviations: HDCV - human diploid cell vaccine; PCEC - purified chick embryo cell; RVA - rabies vaccine adsorbed; ml - milliliter * Preexposure immunization of immunosuppressed travelers is not recommended. If the traveler will be taking chloroquine or mefloquine for malaria chemoprophylaxis, the three-dose series must be completed before antimalarials are begun. If this is not possible, the intramuscular dose and route should be used. Administration of routine booster doses of vaccine depends on exposure risk category as noted in Table 3-12.

Travelers should be advised that any animal bite or scratch should receive prompt local treatment by thorough cleansing of the wound with copious amounts of soap and water; this local treatment will significantly reduce the risk of rabies. Travelers who might have been exposed to rabies should be advised to always contact local health authorities immediately for advice about postexposure prophylaxis and should also contact their personal physician or state health department as soon as possible thereafter. Tables 3-14 and 3-15 provide information on preexposure and postexposure prophylaxis. Routine serologic testing is not necessary for travelers who receive the recommended preeexposure or postexposure regimen with HDCV, PCEC, or RVA vaccines. Exposed travelers previously vaccinated with noncell culture vaccines should receive the complete postexposure regimen unless they have developed a laboratory-confirmed antibody response to the primary vaccination. Serologic testing is still recommended for travelers whose immune response might be diminished by drug therapy or by diseases. Rabies preexposure prophylaxis might not be indicated for travelers to the countries in Table 3-12, and postexposure prophylaxis is rarely necessary after exposures to terrestrial animals in these countries. Chloroquine phosphate (and possibly other structurally related antimalarials such as mefloquine, administered for malaria chemoprophylaxis) might interfere with the antibody response to HDCV when administered by the intradermal (ID) route. The intramuscular (IM) route of preexposure prophylaxis, however, provides a sufficient margin of safety in this setting. HDCV should not be administered by the ID route when chloroquine, mefloquine, or other drugs that might interfere with the immune response are being used. For international travelers, the ID route should be initiated early, to allow the three-dose series to be completed before antimalarials are begun; otherwise, the IM route should be used. PCEC and RVA should never be administered ID. Table 3-15.--Postexposure Immunization.* Immunization Status Vaccine/ Product Dose Number of Doses Schedule (Days) Route Not previously immunized RIG 20 I.U./kg body weight 1 0 Infiltrated at bite site (if possible); remainder intramuscular. HDCV

PCEC RVA 1.0 ml 0 0, 3, 7, 14, 28 Intramuscular Previously immunized HDCV PCEC RVA 1.0 ml 2 0, 3 Intramuscular Abbreviations: RIG - rabies immune globulin; HDCV - human diploid cell [rabies] vaccine; PCEC - purified chick embryo cell; RVA - rabies vaccine adsorbed; I.U. international unit; kg - kilogram; mL - milliliter. * All post-exposure treatment should begin with immediate thorough cleansing of all wounds with soap and water. Pre-exposure immunization with HDCV, PCEC, or RVA; prior post-exposure prophylaxis with HDCV, PCEC, or RVA; or people previously immunized with any other type of rabies vaccine and a documented history of positive antibody response to the prior vaccination. RIG should not be administered. Adverse Reactions Travelers should be advised that they can experience local reactions such as pain, erythema, and swelling or itching at the injection site, or mild systemic reactions, such as headache, nausea, abdominal pain, muscle aches, and dizziness. Approximately 6% of people receiving booster vaccinations with HDCV can experience an immune complex-like reaction characterized by urticaria, pruritus, and malaise. Once initiated, rabies postexposure prophylaxis should not be interrupted or discontinued because of local or mild systemic reactions to rabies vaccine. Precautions and Contraindications Pregnancy.--Pregnancy is not a contraindication to postexposure prophylaxis. Age.--In infants and children, the dose of HDCV, PCEC, or RVA for preexposure or postexposure prophylaxis is the same as that recommended for adults. The dose of RIG for postexposure prophylaxis is based on body weight (Table 3-15).