Animal Control440 Third Street • Room 400 • Columbus, IN 47201 RabiesIntroduction Rabies is a viral infection transmitted in the saliva of infected mammals. The virus enters the central nervous system of the host, causing an encephalomyelitis that is almost always fatal. After the marked decrease of rabies cases among domestic animals in the United States in the 1940s and 1950s, indigenously acquired rabies among humans decreased substantially. In 1950, for example, 4,979 cases of rabies were reported among dogs, and 18 cases were reported among humans. Between 1980 and 1997, 95-247 cases were reported each year among dogs, and on average only two humans cases were reported each year in which rabies was attributable to variants of the virus associated with indigenous dogs. Thus, the likelihood of human exposure to a rabid domestic animal in the United States has decreased greatly. However, during the same period, 12 cases of human rabies were attributed to variants of the rabies virus associated with dogs from outside the United States. Therefore, international travelers to area where canine rabies is still endemic have an increased risk of exposure to rabies. Rabies among wildlife - especially raccoons, skunks, and bats - has become more prevalent since the 1950s, accounting for >85% of all reported cases of animal rabies every year since 1976. Rabies among wildlife occurs throughout the continental United States; only Hawaii remains consistently rabies-free. Wildlife is the most important potential source of infection for both humans and domestic animals in the United States. Since 1980, a total of 21 (58%) of the 36 human cases of rabies diagnosed in the United States have been associated with bat variants. In most other countries - including most of Asia, Africa, and Latin America - dogs remain the major species with rabies and the most common source of rabies among humans. Twelve (33%) of the 36 human rabies deaths reported to the Center for Disease Control and Prevention (CDC) from 1980 through 1997 appear to have been related to rabid animals outside the United States. Although rabies among humans is rare in the United States, every year approximately 16,000-39,000 persons receive postexposure prophylaxis. To appropriately manage potential human exposures to rabies, the risk of infection must be accurately assessed. Administration of rabies postexposure prophylaxis is a medical urgency, not a medical emergency, but decisions must not be delayed. Systemic prophylactic treatments occasionally are complicated by adverse reaction, but these reactions are rarely severe. Data on the safety, immunogenicity, and efficacy of active and passive rabies immunization have come from both human and animal studies. Although controlled human trials have not been performed, extensive field experience from many areas of the world indicates that postexposure prophylaxis wound treatment, passive immunization, and vaccination is uniformly effective when appropriately applied. However, rabies has occasionally developed among humans when key elements of the rabies postexposure prophylaxis regimens were omitted or incorrectly administered (see Treatment Outside the United States). Rabies Biologics Two types of rabies immunizing products are available in the United States
In all postexposure prophylaxis regimens, except for persons previously immunized, both products should be used concurrently. Types of Exposure Rabies is transmitted only when the virus is introduced into bite wounds or open cuts in skin or onto mucous membranes. If no exposure has occurred (i.e., no bite or nonbite exposure), postexposure prophylaxis is not necessary. The likelihood of rabies infection varies with the nature and extent of exposure. Two categories of exposure - bite and nonbite - should be considered. Bite Any penetration of the skin by teeth constitutes a bite exposure. All bites, regardless of location, represent a potential risk of rabies transmission. Bites by some animals, such as bats, can inflict minor injury and thus be undetected.Nonbite Nonbite exposures from terrestrial animals rarely cause rabies. However, occasional reports of transmission by nonbite exposure suggest that such exposures constitute sufficient reason to consider postexposure prophylaxis. The nonbite exposures of highest risk appear to be among persons exposed to large amounts of aerosolized rabies virus and surgical recipients of corneas transplanted from patients who died of rabies. Two cases of rabies have been attributed to probable aerosol exposures in laboratories, and two cases of rabies have been attributed to possible airborne exposures in caves containing millions of free-tailed bats (Tadarida brasiliensis) in the Southwest. The contamination of open wounds, abrasions, mucous membranes, or theoretically, scratches with saliva of other potentially infectious material (such as neural tissue) from a rabid animal also constitutes a nonbite exposure. Other contact by itself, such as petting a rabid animal and contact with blood, urine, or feces (e.g., guano) of a rabid animal, does not constitute an exposure and it not an indication for prophylaxis. Because the rabies virus is inactivated by desiccation and ultraviolet irradiation, in general, if the material containing the virus is dry, the virus can be considered noninfectious. Human-to-Human Transmission Human-to-human transmission has occurred among eight recipients of transplanted corneas. Investigations revealed each of the donors had died of an illness compatible with or proven to the rabies. The eight cases occurred in five countries: Thailand (two cases), India (two cases), Iran (two cases), the United States (one case), and France (one case). Stringent guidelines for acceptance of donor corneas have been implemented to reduce this risk. Apart from corneal transplants, bite and nonbite exposures inflicted by infected humans could theoretically transmit rabies, but no laboratory-diagnosed cases occurring under such situations have been documented. Two nonlaboratory-confirmed cases of human-to-human rabies transmission in Ethiopia have been described. The report route of exposure in both cases was direct salivary contact from another human (a bite and a kiss). Routine delivery of health care to a patient with rabies is not an indication for postexposure prophylaxis unless exposure of mucous membranes or nonintact skin to potentially infectious body fluids has occurred. Adherence to standard precautions as outlined by the Hospital Infection Control Practices Advisory Committee will minimize the risk of exposure. Animal Rabies Epidemiology and Evaluation of Involved Species Bats Rabid bats have been documented in the 49 continental states, and bats are increasingly implicated as important wildlife reservoirs for variants of rabies virus transmitted to humans. Recent epidemiologic data suggest that transmission of rabies virus can occur from minor, seemingly unimportant, or unrecognized bites from bats. The limited injury inflicted by a bat bite (in contrast to lesions caused by terrestrial carnivores) and an often inaccurate recall of the exact exposure history might limit the ability of health-care providers to determine the risk of rabies resulting from an encounter with a bat. Human and domestic animal contact with bats should be minimized, and bats should never be handled by untrained and unvaccinated persons or be kept as pets. In all instances of potential human exposures involving bats, the bat in question should be safely collected, if possible and submitted for rabies diagnosis. Rabies postexposure prophylaxis is recommended for all persons with bite, scratch, or mucous membrane exposure to a bat, unless the bat is available for testing and is negative for evidence of rabies. Postexposure prophylaxis might be appropriate even if a bite, scratch, or mucous membrane exposure is not apparent when there is reasonable probability that such exposure might have occurred. On the basis of the available but sometimes conflicting information from the 21 bat-associated cases of human rabies reported since 1980, in 1-2 cases, a bite was reported; in 10-12 cases, apparent contact occurred but no bite was detected; and in 7-10 cases, no exposure to bats was reported, but an undetected or unreported bat bite remains that most plausible hypothesis. Clustering of bat-associated human cases within the same household has never been reported. Consequently, postexposure prophylaxis should be considered when direct contact between a human and a bat has occurred, unless the exposed person can be certain a bite, scratch, or mucous membrane exposure did not occur. In instances in which a bat is found indoors and there is no history of bat-human contact, the likely effectiveness of postexposure prophylaxis must be balanced against the low risk such exposures appear to present. In this setting, postexposure prophylaxis can be considered for persons who were in the same room as the bat who might be unaware that a bite of direct contact has occurred (e.g., a sleeping person awakens to find a bat in the room or an adult witnesses a bat in the room with a previously unattended child, mentally disabled person) and rabies cannot be ruled out by testing the bat. Postexposure prophylaxis would not be warranted for other household members. Wild Terrestrial Carnivores Raccoons, skunks, foxes, and coyotes are the terrestrial animals most often infected with rabies. All bites by such wildlife must be considered possible exposures to the rabies virus. Postexposure prophylaxis has been initiated and subsequent immunofluorescence testing shows that the exposing animal was not rabid, postexposure prophylaxis can be discontinued. Signs of rabies among wildlife cannot be interpreted reliable; therefore, any such animal that exposes a person should be euthanized at once (without unnecessary damage to the head) and the brain should be submitted for rabies testing. If the results of testing are negative by immunofluorescence, the saliva can be assumed to contain no virus, and the person bitten does not require postexposure prophylaxis. Other Wild Animals Small rodents (e.g., squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) an lagomorphs (including rabbits and hares) are almost never found to be infected with rabies and have not been known to transmit rabies to humans. From 1990 through 1996, in areas of the country where raccoon rabies was enzootic, woodchucks accounted for 93% of the 371 cases or rabies among rodents reported to CDC. In all cases involving rodents, that state of local health department should be consulted before a decision is made to initiate antirabies postexposure prophylaxis. The offspring of wild animals crossbred to domestic dogs and cats (wild animal hybrids) are considered wild animals by the National Association of State and Public Health Veterinarians (NASPHV) and the Council of State and Territorial Epidemiologists (CSTE). Because the period of rabies virus shedding in these animals is unknown, these animals should be euthanized and tested rather than confined and observed when they bite humans. Wild animals and wild animal hybrids should not be kept as pets. Animals maintained in United States Department of Agriculture-licensed research facilities or accredited zoological parks should be evaluated on a case-by-case basis. Domestic Dogs, Cats, and Ferrets The likelihood of rabies in a domestic animal varies by region; hence, the need for postexposure prophylaxis also varies. In the continental United States, rabies among dogs is reported most commonly along the United States-Mexico border and sporadically in areas of the United States with enzootic wildlife rabies. During most of the 1990s, more cats than dogs were reported in the United States. The majority of these cases were associated with the epizootic of rabies among the raccoons in the eastern United States. The large number of rabies-infected cats might be attributed to fewer vaccination laws, fewer leash laws, and the roaming habits of cats. In many developing countries, dogs are the major vector of rabies; exposures to dogs in such countries represent an increased risk of rabies transmission. On the basis of new information regarding rabies pathogenesis and viral shedding patterns in ferrets, ferrets are now considered in this category with dogs and cats rather than as wild terrestrial carnivores. A healthy domestic dog, cat, or ferret that bites a person may be confined and observed for 10 days. Any illness in the animal during confinement or before release should be evaluated by a veterinarian and reported immediately to the local public health department. If signs suggestive of rabies develop, the animal should be euthanized and its head removed and shipped, under refrigeration, for examination by a qualified laboratory. If the biting animal is stray or unwanted, it should either be observed for 10 days or be euthanized immediately and submitted for rabies examination. Circumstances of Biting Incident and Vaccination Status of Exposing Animal An unprovoked attack by an animal is more likely than a provoked attack to indicate that the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as provoked. A currently vaccinated dog, cat, or ferret is unlikely to become infected with rabies. Treatment Of Wounds And Immunization The essential components of rabies postexposure prophylaxis are wound treatment and, for previously unvaccinated persons, the administration of both RIG and vaccine. Persons who have been bitten by animals suspected pr proven to be rabid should begin postexposure prophylaxis immediately. Incubation periods of 1 year have been reported in humans. Thus, when a documented or likely exposure has occurred, postexposure prophylaxis is indicated regardless of the length of the delay, provided the clinical signs of rabies are not present.In 1977, the World Health Organization recommended a regimen of RIG and six doses of HDCV over a 90-day period. This recommendation was based on studies in Germany and Iran. When used this way, the vaccine was found to be safe and effective in protecting persons bitten by animals proven to be rabid and induced an excellent antibody response in all recipients. Studies conducted in the United States by CDC have documented that a regimen of one dose of RIG and five doses of HDCV over a 28-day period was safe and induced an excellent antibody response in all recipients. Clinical trials with RVA and PCEC have demonstrated immunogenicity equivalent to that of HDCV. Treatment of Wounds Immediate and thorough washing of all bite wounds and scratches with soap and water a virucidal agent such as a providone-iodine solution irrigation are important measures for preventing rabies. In studies of animals, thorough wound cleansing alone without other postexposure prophylaxis has been shown to reduce markedly the likelihood of rabies. Tetanus prophylaxis and measures to control bacterial infection also should be administered as indicated. The decision to suture large wounds should take into account cosmetic factors and the potential for bacterial infections. Immunization Postexposure antirabies vaccination should always include administration of both passive antibody and vaccine, with the exception of persons who have previously received complete vaccination regimens (preexposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have had documented rabies antibody titers. These persons should receive only vaccine (see Postexposure Therapy for Previously Vaccinated Persons. The combination of RIG and vaccine is recommended for both bite and nonbite exposures (see Rationale for Treatment), regardless of the interval between exposure and initiation of treatment. Adverse Reactions HDCV, RVA, PCEC Reactions after vaccination with HDCV, RVA, and PCEC are less serious and less common than with previously available. In previous studies with HDCV, local reaction (e.g., pain, erythema, and swelling or itching at the injection site) have been reported among 30%-74% of recipients. Systemic reactions (e.g., headache, nausea, abdominal pain, muscle aches, and dizziness) have been reported among 5%-40% of recipients. Three cases of neurologic illness resembling Guillain-Barre syndrome that resolved without sequelae in 12 weeks have been reported. In addition, other central and peripheral nervous system disorders have been temporally associated with HDCV vaccine, but a causal relationship has not been established in these reports. An immune complex-like reaction occurred among approximately 6% of persons who received booster doses of HDCV 2-21 days after administration of the booster does. The patients developed generalized urticaria, sometimes accompanied by arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise. In no cases have these reactions been life threatening. This reaction occurred less frequently among persons receiving primary vaccination. The reactions have been associated with the presence of betapropiolactone-altered human albumin in the HDCV and the development of immunoglobulin E (IgE) antibodies to this allergen. Rabies Immune Globulin (Human) Local pain and low-grade fever might follow receipt of RIG. Although not reported specifically for RIG, angioneurotic edema, nephrotic syndrome, and anaphylaxis have been reported after infection of immune globulin (IG), a product similar in biochemical composition but without antirabies activity. These reactions occur so rarely that a causal relationship between IG and these reactions has not been established. Both formulations of RIG, BayRab and Imogam Rabies-HT, undergo multiple viral clearance procedures during preparation. There is no evidence that nay viruses have ever been transmitted by commercially available RIG in the United States. Vaccines and Immune Globulins Used in Other Countries Many developing countries use inactivated nerve tissue vaccines made from the brains of adult animals or suckling mice. Nerve tissue vaccine (NTV) is reported to induce neuroparalytic reactions among approximately 1 per 200 to 1 per 2,000 persons vaccinated; suckling mouse brain vaccine (SMBV) causes reaction in approximately 1 per 8,000 persons vaccinated. The vaccines HDCV, PCEC, PDEV, and purified vero cell rabies vaccine (PVRV) are cell culture-derived and not of nerve tissue origin. In addition, unpurified antirabies serum of equine origin might still be used in some countries where neither RIG nor ERIG are available. The use of this antirabies serum is associated with higher rates of serious adverse reactions, including anaphylaxis. Management of Adverse Reactions Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Usually, such reactions can be successfully managed with antiinflammatory and antipyretic agents, such as ibuprofen or acetaminophen. When a person with a history of serious hypersensitivity to rabies vaccine must be revaccinated, antihistamines can be administered. Epinephrine should be readily available to counteract anaphylactic reactions, and the person should be observed carefully immediately after vaccination. Although serious systemic, anaphylactic, or neuroparalytic reactions are rare during and after the administration of rabies vaccines, such reactions pose a serious dilemma for patient and the attending physician. A patient's risk of acquiring rabies must be carefully considered before deciding to discontinue vaccination. Advice and assistance on the management of serious adverse reaction for persons receiving rabies vaccines may be sought from the state health department or CDC. All serious systemic, neuroparalytic, or anaphylactic reaction should be reported to the Vaccine Adverse Event Reporting System (VAERS) via a 24-hour toll-free telephone number (800) 822-7967). Precautions and Contraindications Immunosuppression Corticosteroids, other immunosuppressive agents, antimalarials, and immunosuppressive illnesses can interfere with the development of active immunity after vaccination. For persons with immunosuppression, preexposure prophylaxis should be administered with the awareness that the immune response might be inadequate (see Primary or Preexposure Vaccination). Patients who are immunosuppressed by disease or medications should postpone preexposure prophylaxis is indicated. When this course is not possible, immunosuppressed persons who are at risk for rabies should be vaccinated by the IM route and their antibody titers checked. Failure to seroconvert after the third dose should be managed in consultation with appropriate public health officials (see Preexposure Vaccination and Serologic Testing). Immunosuppressive agents should not be administered during postexposure therapy unless essential for the treatment of other conditions. When postexposure prophylaxis is administered to an immunosuppressed person, it is especially important that a serum sample be tested for rabies antibody to ensure that an acceptable antibody response has developed. Pregnancy Because of the potential consequences of inadequately treated rabies
exposure, and because there is no indication that fetal abnormalities
have been associated with rabies vaccination, pregnancy is not considered
a contraindication to postexposure prophylaxis. If the risk of exposure
to rabies is substantial, preexposure prophylaxis might also be
indicated during pregnancy. |
