Rabies Postexposure Prophylaxis

VACCINES AND VACCINATIONS

0195-5616/01 $15.00 + .00

RABIES POSTEXPOSURE PROPHYLAXIS Human and Domestic Animal Considerations M. Gayne Fearneyhough, BS, DVM

Since the middle of this century, an average of one or two human rabies cases has been reported annually in the United States. The 1996 estimated cost for rabies biologic agents required for postexposure prophylaxis (PEP) for people exposed to a rabid or potentially rabid animal was between $26.5 and $65.3 million. 8 In three studies conducted since 1980, the total annual expenditure to prevent rabies in the United States was found to be at least $230 million, and it may be as much as $1 billion annually? A cursory analysis of the public health significance of rabies in the United States could easily result in the conclusion that a disproportionate number of resources are allocated to the disease, especially when the numbers of cases of human rabies and rabies in domestic animals have declined over the last 50 years. A more detailed examination of the epidemiologic nature of rabies reveals a valid cause for concern, however, with rapidly expanding epizootics of wildlife rabies in raccoons in the eastern United States, in foxes in Texas and the northeastern United States, and in coyotes in Texas. An additional cause for concern is the identification of a viral variant transmitted by bats, which may represent an increased public health threat. That threat has caused modification to the Centers for Disease Control and Prevention (CDC) recommendations for PEP in people experiencing potential exposure to a bat. 4 Prior Director, Oral Rabies Vaccination Program, Texas Department of Health, Zoonosis Control Division, Austin, Texas from 1993-2000

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Although rabies causes only one or two human deaths annually in the United States, it is important to understand an estimated 40,000 to 100,000 human deaths result worldwide from rabies each yearP Consequently, as a society, we tend to have a strong and sometimes unreasonable fear of exposure to the rabies virus. That fearful response may be attributed in part to the graphic depiction of the disease by the entertainment industry in motion pictures such as "Old Yeller" and "Cujo." Fear of rabies may stimulate someone with a potential exposure to rabies to seek medical intervention and thereby save a human life. Conversely, fear also causes patients to demand treatment when a threat does not exist and may result in the inappropriate use of valuable medical resources. Practicing veterinarians, medical professionals, or public health workers may find that they are the most informed participants in a risk analysis process after a potential human or animal exposure to rabies. When administered according to recommendations provided by the Advisory Committee on Immunization Practices (ACIP), PEP has been shown to be essentially 100% effective. Given that rabies is universally fatal, it is essential that accurate and timely decisions be made concerning the administration of PEP. A 1946 report by the Committee on Animal Health of the National Research Council determined that rabies was a preventable disease and proposed that a coordinated effort to achieve that goal be developed under the leadership of the United States Department of Agriculture (USDA) and individual state veterinariansY Control measures that focused on domestic animal vaccination, local animal control programs, public education, and wildlife depopulation were proposed. In 1938, there were 9412 cases of rabies reported in animals (mostly in domestic species) and 47 human deaths.12 As late as 1960, most rabies cases were still reported in domestic species. Beginning in 1990, however, there was a dramatic increase in reported cases of wildlife rabies, primarily attributed to the raccoon rabies epizootic in the eastern United States. From 1990 to 1993, a 225% increase was reported in raccoon rabies cases (from 1812 to 5885) in the mid-Atlantic and northeastern states. By 1996, more than 90% of the 7124 animal rabies cases reported in the United States to the CDC were in wildlife species. 8 ,13 Although a coordinated national program did not develop, some or all of the principles for rabies control that were proposed in 1946 were employed at the state and local levels. It is reasonable to assume that those measures have had a favorable impact on the reduction of human and domestic animal rabies cases over the last 50 years. Nevertheless, the changing face of rabies with the identification of new animal reservoirs and new viral variants has necessitated that rabies control and PEP recommendations constantly evolve. That evolutionary process should

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employ the application of new technology to continue to prevent human deaths through the appropriate application of PEP and the development of innovative programs to reduce the presence of rabies in wildlife. RABIES RISK ASSESSMENT

The evaluation process to ascertain an individual's risk of exposure to rabies first involves the determination of whether a bite or nonbite exposure may have occurred. If an exposure has occurred that could result in rabies virus transmission, it is critical that proper wound management techniques be used immediately. The simple process of proper wound cleansing and irrigation with adequate soap and water can reduce the potential for rabies. 2 Assessment of the wound and appropriate use of antibiotic therapy and tetanus prophylaxis should also be considered. The end result of what can be a complicated risk assessment process is the decision of whether to initiate PEP. A decision to withhold PEP while awaiting the outcome of a laboratory test or the outcome of a quarantine period for the biting domestic animal constitutes a decision to not treat the patient at that time. If a patient has been exposed to rabies, the greatest chance for survival may depend on prompt initiation of PEP. The process of reaching a risk assessment decision can be complicated and clouded by emotional and legal considerations. The following summary of risk assessment considerations is taken from the recommendations of the ACIP and the National Association of State Public Health Veterinarians (NASPHV) as published in the Morbidity and Mortality Weekly Report. 2, 10 These recommendations constitute the minimum criteria that should be considered in evaluating a patient's risk for rabies exposure. Figure 1 represents a rabies PEP decision tree. Type of Exposure

The primary mechanism of rabies transmission involves a bite wound, which allows the passage of virus-containing saliva across a previously intact skin barrier. Bites to the face and hands carry the highest risk, but the site of the bite should not influence the decision to begin PEP. Nonbite exposure by means of scratches, abrasions, open wounds, or mucous membranes that are exposed to saliva or other infective material (i.e., brain tissue, cerebrospinal fluid) may also constitute an exposure. Petting a rabid animal; exposure of intact skin to blood, urine, or feces of a rabid animal; or contact with fluids that may

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Did the person have a bite exposure?

YES YES

Was there an exposure of broken skin or mucous membranes to saliva or CSF? See text section on Wild Animal Bites for the special case of exposure to bats.

NO

Is the animal a high-risk species in an epizootic area, was there a bite on the head or shoulders, or will it take more than 48 hours to have the animal tested for rabies?

Did the dog, cat, or ferret die with signs of rabies in the IO-day observation period?

Was rabies confirmed by direct fluorescent antibody testing of the brain?

Figure 1. Rabies postexposure prophylaxis decision tree.

have been infective but have dried does not constitute an exposure. Nonbite exposure from aerosolized rabies virus in caves, laboratory settings, or organ transplants (i.e., corneas) has occurred but represents unlikely an exposure situation.

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Exposing Animal

Wild Animal Bites

Bites by wild carnivores and bats should be considered an exposure to rabies and require initiation of PEP for the patient. The biting animal should be humanely killed immediately, and the brain should be tested for rabies, especially in species that may be defined as high risk for rabies exposure such as raccoons, skunks, foxes, and bats. The recent epizootic of canine rabies in coyotes along the Texas-Mexico border and the practice of translocating coyotes for hunting purposes may make it prudent to also consider them a high-risk species. PEP may be delayed if the bite occurs in a geographic area of the United States that is free of terrestrial rabies and if the results of immunofluorescence testing are available within 48 hours. If treatment is initiated and the biting animal is shown not to be rabid, treatment may be discontinued. Exotic animals and valuable specimens that have been confined and have been determined by public health authorities to represent a limited risk may be quarantined for 30 days in lieu of testing. Rodent and lagomorph species are almost never found to be infected with rabies, and local health departments should be consulted concerning bites by those animal groups. Rabies in groundhogs accounted for 70% of the 179 cases among rodents reported to the CDC from 1971 through 1988, however.2 An analysis of data reported by Krebs and associates 9 from 1991 through 1996 indicates an annual average of 52 cases of rabies in groundhogs, with most of those cases attributed to the raccoon variant of the rabies virus. The Conference of State and Territorial Epidemiologists and the NASPHV consider exotic pets and domestic animals crossbred with wild animals to be wild animals. 10 A bite by any of those animals should be handled as an exposure to a wild animal. Modifications to PEP recommendations were presented to the ACIP in 1996, because data indicated that bats were associated with an increasing number of human rabies cases. From 1990 through 1996, bat rabies variants were associated with 15 of 17 indigenously acquired cases of human rabies. An identifiable bite was reported in only 1 of those cases, suggesting that minimal or unnoticed physical contact with bats may result in viral transmission. s In situations in which a bat is physically present and the person(s) cannot reasonably exclude the possibility of a bite exposure, PEP should be given unless prompt capture and testing of the bat have excluded rabies virus infection. 3 This recommendation has particular significance for children, mentally challenged adults, and intoxicated individuals, who may be unable to responsibly assess whether contact with a bat has occurred. If a bat is found in a room with an unattended child or is found present in a room in which a child

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or adult was sleeping and physical contact cannot be excluded, PEP should be initiated immediately, and, if available, the bat should be tested for rabies. Negative immunofluorescence antibody testing results from a certified laboratory are justification for discontinuing PEP. Domestic Animal Bites

The NASPHV makes recommendations to be used in the management of animals that bite human beings (Ref. 10, p 83).10 Circumstances of the Bite

An unprovoked bite by a domestic animal may constitute an increased risk for rabies in the biting animal and contributes to a decision to initiate PEP for the patient. People fear being bitten by an animal; thus, it is reasonable to assume that most bites inflicted on human beings by domestic animals are not intentionally provoked. It is important to emphasize that the human definition of provocation may not be consistent with conditions that elicit aggressive or defensive behavior in a domestic species. Although not often seen as provocative behavior by people, actions such as invading the ill-defined physical territory of an animal, disturbing an animal during eating, staring into the eyes of a dominant animal, playing by children that may attempt to force an animal to the ground, and blowing into the face of an animal are but a few examples of human behavior that may produce an aggressive response in a normal animal. Vaccination Status of the Exposing Animal

Knowledge that a biting domestic animal is currently vaccinated with a vaccine licensed for that species does not remove all concern for involvement of rabies, because no vaccine can be considered to be 100% effective. Animal vaccines licensed for use in the United States have achieved a high level of immunogenicity, however, and their use in a domestic species for which a license has been approved markedly reduces the potential for rabies involvement. Knowledge of a current vaccination in the biting animal, when combined with a lack of epidemiologic evidence of terrestrial rabies in the geographic area and reduced risk associated with conditions of the bite, may allow for justification of a la-day quarantine period for a biting animal. Employing a la-day quarantine period has obvious benefits to the owner of a valuable animal compared with euthanizing the animal and testing the brain. If the

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animal is available for quarantine and the risk assessment process indicates a low probability for rabies, PEP can be delayed for the patient; however, PEP should be initiated immediately at the first sign of rabies in the quarantined animal (Table 1). RABIES IMMUNIZING PRODUCTS FOR USE IN HUMAN BEINGS

There are two types of immunizing products for use in human beings: immune globulins that provide rapid passive immune protection for a short time (half-life of about 21 days) and vaccines that induce an active immune response (requires about 7-10 days to develop, but immunity may persist for at least 1 year). Both types of products should be used concurrently for rabies PEP in those persons who have never received prior immunization against rabies. It is recommended that the package insert be consulted before any of these products is used. 14 Table 1. CURRENT ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES RABIES POSTEXPOSURE HUMAN PROPHYLAXIS GUIDE Animal Type

Dogs and cats

Skunks, raccoons, bats, foxes, and most other carnivores; groundhogs

Livestock, rodents, and lagomorphs (rabbits and hares)

Evaluation and Disposition of Animal

Postexposure Prophylaxis Recommendations

Healthy and available for 10 days

Should not begin PEP unless animal develops clinical signs of rabies* Immediate PEP Consult public health officials Immediate PEP

Rabid or suspect rabid Unknown or escaped Regarded as rabid unless geographic area is known to be free of rabies or until animal is proved negative by laboratory testt Consider individually

Consult public health officials; bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other rodents, rabbits, and hares almost never require antirabies treatment

*During the lO-day holding period, begin treatment with human rabies immune globulin and human diploid cell vaccine or purified chick embryo cell culture at first sign of rabies in a dog or cat that has bitten someone. The animal with clinical signs should be euthanized immediately and tested. tThe animal should be euthanized and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative. PEP = postexposure prophylaxis. From Centers for Disease Control and Prevention: Rabies prevention-United States, 1991, recom· mendations of the Immunization Practices Advisory Committee (ACIP). MMWR Morb Mortal Wkly Rep 40(RR-3):1-19, 1991.

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Table 2. POSTEXPOSURE TREATMENT PRODUCTS-HUMAN RABIES IMMUNE GLOBULlN* Product Name

Imogam BayRab

Manufacturer

Pasteur Merieux Connaught Laboratories (Swiftwater, PA) Bayer Laboratories (Pittsburgh, PA)

*Administered at time of first dose of vaccine only. Patient weight is needed to determine dose. Dose is 20 IU/kg (2 mL per 331b).

Rabies Immune Globulin

Human rabies immune globulin (HRIG) (Imogam Rabies-HT, Pasteur Merieux Connaught, Swiftwater, PA; and BayRab, Bayer Laboratories, Pittsburgh, PA) is antirabies gamma globulin concentrated by cold ethanol fractionation from the plasma of immunized human donors. Rabies neutralizing antibody content is standardized to contain 150 IV / mL. It is supplied in 2-mL (300 10) and 10-mL (1500 10) vials for pediatric and adult use, respectively (Table 2). Imogam Rabies-HT has received an additional heat treatment step to further reduce the risk of the transmission of known or unknown blood-borne viruses. Vaccines Human Diploid Cell Vaccine

Human diploid cell vaccine (HDCV) is an inactivated virus vaccine prepared from rabies virus grown in human diploid cell culture and then inactivated (Table 3). Vaccine is supplied as I-mL single-dose vials of freeze-dried vaccine with accompanying diluent for intramuscular (1M) injection (Imovax Rabies Vaccine, Pasteur Merieux Connaught) and O.I-mL single-dose syringes of freeze-dried vaccine with accompanying diluent for pre-exposure intradermal use (Imovax Rabies LD., Pasteur Merieux Connaught). Both formulations must be used immediately after reconstitution.

Table 3. POSTEXPOSURE TREATMENT PRODUCTS-HUMAN RABIES VACCINES Product Name

Imovax: human diploid cell vaccine RabAvert: purified chick embryo cell culture

Manufacturer

Pasteur Merieux Connaught Laboratories (Swiftwater, PA) Chiron Behring GrnhH & Company (Hessen, Germany)

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Purified Chick Embryo Cell Culture

Purified chick embryo cell (PCEC) culture is a sterile freeze-dried vaccine obtained by growing the Flury-fixed virus strain, low-egg passage in primary cultures of chicken fibroblasts (see Table 3). PCEC culture (RabAvert, Chiron Behring GrnhH & Company, Hessen, Germany) is licensed in the United States for 1M use in pre-exposure immunization and PEP. The schedules and dosage for PCEC culture are the same as for HDCV. It may be used as a booster dose even if another rabies vaccine was used for the primary series. Serious adverse reactions associated with some rabies vaccines include systemic, anaphylactic, and neuroparalytic reactions. Serious adverse reactions occur at lower rates with HDCV or PCEC vaccines than with previously available types of rabies vaccine.

POSTEXPOSURE PROPHYLAXIS IMMUNIZATION PROTOCOL

Postexposure antirabies immunization should include administration of rabies antibody (HRIG) and vaccine (HDCV or PCEC culture). An exception to this guideline is made for exposed persons who have been previously immunized with the recommended pre-exposure or postexposure regimens of HDCV or PCEC culture (or who have been immunized with other types of vaccines and have documented an adequate rabies antibody titer). In those cases, HRIG would not be given, and only two doses of vaccine would be given on day a and day 3 (Table 4). The combination of immune globulin and vaccine is recommended for persons not previously immunized for bite exposures and nonbite exposures, regardless of the interval between exposure and treatment. The sooner treatment is begun after exposure, the better is the chance of effectiveness. If there was a delay in recognizing a rabies exposure, treatment may be started even months after that exposure occurred. Five 1-mL doses of HDCV or PCEC culture should be given 1M in the deltoid region in adults or on the anterolateral thigh in infants. The intradermal route should not be used for PEP. The first dose should be given as soon as possible after exposure; additional doses should be given on days 3, 7, 14, and 28 after the first dose. Antibody response after the recommended vaccination regimen has been uniformly satisfactory; thus, routine postvaccination serologic testing is not normally recommended. In unusual instances, however, such as when the patient is immunodeficient or immunosuppressed, serologic testing (rapid fluorescent focus inhibition test) is indicated. This test is available with fast

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Table 4. RABIES POSTEXPOSURE PROPHYLAXIS SCHEDULE IN THE UNITED STATES Patient Vaccination Status

Not previously vaccinated

Local wound cleansing

HR1G

Vaccine Previously vaccinated:!:

Regimen"

Treatment

Local wound cleansing

HRlG Vaccine

All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water 20 IV /kg of body weight; as much as possible of the full dose should be infiltrated into and around the wound(s), and the remainder should be administered 1M at an anatomic site distant from vaccine administration; HRlG should not be administered in the same syringe as vaccine; Because HRlG may partially suppress active production of antibody, no more than the recommended dose should be given 1 mL of HDCV or PCEC culture 1M (deltoid areat) on days 0, 3, 7, 14 and 28 All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water HRIG should not be administered 1 mL of HDCV or PCEC culture 1M (deltoid areat) on days and 3

°

*These regimens are applicable for all age groups, induding children. tThe deltoid area is the only acceptable site of vaccination for adults and older children. For younger children, the outer aspect of the thigh may be used. Vaccine should never be administered in the gluteal area. :j:Any person with a history of pre-exposure vaccination with HDCV or PCEC, prior postexposure prophylaxis with HDCV or PCEC, or previous vaccination with any other type of rabies vaccine and documented history of antibody response to the prior vaccination. HRIG = human rabies immune globulin; 1M = intramuscularly; HDCV = human diploid cell vaccine; PCEC = purified chick embryo cell From Texas Department of Health: Rabies Prevention in Texas 1997. Austin, TX, Texas Department of Public Health stock no 6-108, 1997; with permission.

turnaround through the Department of Veterinary Diagnostics, Veterinary Medical Center, Kansas State University, Manhattan, Kansas 66506 (telephone: 785-532-5650). The selection of sites for 1M injections of vaccine seems to be critical

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for vaccine efficacy. In adults and larger children, HDCV or PCEC culture should be given in the deltoid area. In infants and small children, the anterolateral thigh should be used. In the two laboratory-confirmed cases of human rabies after postexposure treatment with HDCV and HRIG within 24 hours, the HDCV was administered in the gluteal area. Presumably, subcutaneous fat in the gluteal area may interfere with proper 1M administration of the vaccine and thus reduces the immunogenicity of the vaccine. HRIG is administered only once at the beginning of antirabies prophylaxis to provide immediate antibodies until the patient responds to vaccination with active production of antibodies. If HRIG was not given at the initiation of vaccination, it can be given up to the eighth day after the first dose of vaccine. From the eighth day on, HRIG is not indicated, because an antibody response to the vaccine is presumed to have occurred. The recommended dose of HRIG is 20 IU Ikg or approximately 9 IU lIb (2 mL per 33 lb) of body weight. As much of the full dose of HRIG as possible should be thoroughly infiltrated into and around the wound(s). Any remaining volume should be administered 1M at a site distant from vaccine inoculation. No more than the recommended dose of HRIG should be given because it may partially suppress active production of antibody. POSTEXPOSURE PROPHYLAXIS TREATMENT OUTSIDE THE UNITED STATES

If PEP treatment is begun outside the United States with locally produced biologic agents, it may be desirable to provide additional treatment when the patient reaches the United States. For specific advice in such cases, contact the local health department. POSTEXPOSURE THERAPY OF PREVIOUSLY IMMUNIZED PERSONS

Pre-exposure immunization does not remove the need for PEP; it merely reduces the extent of treatment. On exposure to rabies, an immunized person who was vaccinated with the recommended regimen of HDCV or PCEC culture or who has previously demonstrated rabies antibody should receive two 1M doses (1 mL each) of HDCV or PCEC culture, one immediately and one 3 days later (see Table 4). HRIG should not be given in these cases. Full primary postexposure antirabies treatment (HRIG plus five doses of HDCV or PCEC culture) may be

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necessary in the case of unknown immune status in a previously vaccinated person who did not receive the recommended HDCV or PCEC regimen. In such cases, if antibody can be demonstrated in a serum sample collected before vaccine is given, treatment can be discontinued after at least two doses of HDCV or PCEC culture.

ACCIDENTAL HUMAN EXPOSURE TO ANIMAL RABIES VACCINE

Accidental inoculation or vaccine contact with mucous membranes may occur in human beings during administration of rabies vaccines to animals. Such exposure to inactivated rabies vaccine constitutes no known rabies hazard.

PRECAUTIONS AND CONTRAINDICATIONS Immunosuppression

Corticosteroids and other immunosuppressive agents, antimalarials, and immunosuppressive illnesses (such as HIV infection) can interfere with the development of active immunity and predispose the patient to the development of rabies. Immunosuppressive agents should not be administered during postexposure therapy unless they are essential for the treatment of other conditions. When rabies PEP is administered to persons receiving corticosteroids or other immunosuppressive therapy or to persons having an immunosuppressive illness, it is especially important that the patient be tested for rabies antibody to ensure that an adequate response has developed.

Pregnancy

Because of the potential consequences of an inadequately treated rabies exposure and limited data indicating that fetal abnormalities have been associated with rabies vaccination, pregnancy is not considered a contraindication to PEP. If a substantial unavoidable risk of exposure to rabies exists, pre-exposure prophylaxis may also be indicated during pregnancy.

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Allergies

Persons with histories of hypersensitivity should be given rabies vaccines with caution. When a patient with a history suggesting hypersensitivity to HDCV or PCEC culture must be given that vaccine, antihistamines can be provided; epinephrine should be readily available to counteract anaphylactic reactions, and the person should be carefully observed. MANAGEMENT OF PETS EXPOSED TO RABID ANIMALS

The management of cases of domestic animals exposed to rabies can be difficult because of the lack of an immediate perceived threat to human life. The exposure incident obviously could later result in human exposure if the domestic animal should develop rabies. As a result, the recommendation normally has been to sacrifice the exposed animal. Management of these cases may also be further complicated by the emotional value of the animal as well as conflict over the rights of ownership of private property and disposition of that property when little or no human health risk exists. The NASPHV recommends postexposure management for animals exposed to a rabid animal. 8 Confusion has occurred with respect to (1) the lO-day observation period for a dog, cat, or ferret that has bitten or scratched a human being and (2) the period of strict isolation required for an unvaccinated dog, cat, or ferret that has been exposed to a rabid animal. Generally, when clinical symptoms of rabies are first evident, the rabies virus also becomes present in the saliva, and a dog, cat, or ferret survives no longer than 3 to 5 days. If the animal is clinically normal 10 days after the biting incident, it is not considered likely for rabies virus to have been present in its saliva at the time of the bite. As a result, exposure to rabies virus could not have resulted from the bite, and PEP is not indicated. A dog, cat, or ferret may develop rabies more than 10 days after having bitten a person, but the animal would not be considered to have been infective at the time of the bite. The la-day observation period is not applicable for a dog, cat, or ferret exposed to a rabid animal. The average incubation time for rabies in those species is generally 3 to 8 weeks; thus, an observation period of 45 days for vaccinated animals and 180 days for unvaccinated animals is recommended. Consequently, the lO-day observation period is useful in ensuring that a dog, cat, or ferret was not able to transmit rabies at the time of a biting incident, but it is not applicable for those species under observation after an exposure to a rabid animal.

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POSTEXPOSURE PROPHYLAXIS JUSTIFICATION FOR DOMESTIC ANIMALS

The primary concern of the risk assessment process to determine the appropriateness of PEP for a human patient must be the patient's safety. Rabies is universally fatal; thus, there is a tendency to administer PEP to the human patient when there may be even a limited potential for rabies exposure. That conservative approach to management of the human patient has also resulted in recommendations for sacrificing an animal exposed to or potentially exposed to rabies. Such recommendations are not usually based on a callous approach to the value of the animal but rather on a concern that the exposed animal might later develop rabies and represent a serious public health threat. The reluctance to advocate the use of PEP in animals is also complicated by the fact that there are limited scientific data published to demonstrate the effectiveness of PEP when administered to domestic animals. A 1996 study by Clark and Wilsons does provide data to demonstrate the effectiveness of PEP in unvaccinated domestic animals. This retrospective study was conducted using two PEP protocols on 1345 unvaccinated domestic animals that were exposed to rabies and reported to the Texas Department of Health over a 16-year period. The first PEP protocol was used from 1979 through 1987 and involved 713 animals (440 dogs; 57 cats; 145 cattle; 53 horses; and 18 sheep, goats, and pigs). The exposed animals were immediately vaccinated and revaccinated 1 month before release from a 6-month period of isolation (there is no USDA-licensed vaccine for goats and pigs). The second protocol was used from 1988 through 1994 and involved 632 animals (406 dogs; 106 cats; 69 cattle; 43 horses; 7 sheep, pigs, and goats; and 1 llama). In the second protocol, the exposed animals were vaccinated immediately and given booster vaccinations during the third and eighth weeks of a 90day isolation period (there is no USDA-licensed vaccine for llamas). This study determined that 711 of 713 animals (99.7%) given PEP using the first protocol and 629 of 632 animals (99.5%) given the second protocol survived. Another study in 1991 conducted by Blancou and associates 1 to determine the efficacy of the human PEP protocol used 68 sheep experimentally infected with fox rabies virus. The infected sheep were divided into three groups and were given cell culture vaccine on days 0, 3, 7, and 14; HRIG at 26 IU/kg on day 0; or a combination of vaccine and immune globulin. Seventy-one percent of the controls died; the treatment protocol using a combination of vaccine and immune globulin was found to be 100% effective. These results seem to indicate that there may be justification for PEP for domestic animals. Additional studies are needed to identify animal PEP protocols capable of producing a high

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level of survivability, conforming to public health concerns, and yet being economically applicable to domestic animals. SUMMARY

The emphasis on rabies control and prevention in the United States seems to be a function of our perception of proximity of the threat. Wildlife rabies epizootics within a state may be of little concern to the uninformed urban dweller. Additionally, many parts of the western United States are free of terrestrial rabies; were it not for the presence of bat rabies, people in those areas would likely interpret rabies control as a minor public health concern. It is essential that federal, state, and local public health programs emphasize the importance of rabies control through activities that include rabies education, sponsorship of legislated requirements for domestic animal vaccination, support for local animal control programs, and the promotion of recommendations that encourage the appropriate use of PEP. We are almost guaranteed that rabies is going to remain a major public health issue well into the next century because of expanding wildlife rabies epizootics, identification of new rabies viral variants with increased public health concern, emotional and legal concerns associated with rabies exposure, and increasing national cost associated with rabies control and prevention. Nevertheless, the development of new laboratory technology that allows an understanding of the epidemiologic nature of the rabies virus based on an evolving genetic history and the interrelationship with wildlife reservoirs should allow access to valuable tools for rabies control. When combined with programs using new developments in oral rabies vaccine that can immunize whole populations of wildlife reservoirs, that technology offers encouragement in our effort to control one of the diseases of antiquity.6 ACKNOWLEDGMENTS The author thanks Dr. Erik Svenkerud and Pamela of Health for their assistance and editorial comments.

J. Wilson of the Texas Department

References 1. Blancou J, Baltazar RS, Molli I: Effective postexposure treatment of rabies-infected sheep with rabies immune globulin and vaccine. Vaccine 9:432-437, 1991 2. Centers for Disease Control and Prevention: Rabies prevention-United States, 1991, recommendations of the Immunization Practices AdviSory Committee(ACIP). MMWR Morb Mortal Wkly Rep 40(RR-3):1-19, 1991 3. Centers for Disease Control and Prevention: Rabies prevention. MMWR Morb Mortal Wkly Rep 445:209,1996

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4. Childs JE, Krebs JW, Rupprecht CE: Epidemiology of bat rabies in the USA. Presented at the Eighth Annual International Meeting of Rabies in the Americas, Kingston, Ontario, Canada, November 2--{), 1997 5. Clark KA, Wilson PJ: Postexposure rabies prophylaxis and preexposure rabies vaccination failure in domestic animals. JAVMA 208:1827-1830,1996 6. Fearneyhough MG, Wilson pJ, Clark KA, et al: Results of an oral rabies vaccination program for coyotes. JAVMA 212:498-502,1998 7. Fishbein DB, Robinson LE: Rabies. N Engl J Med 329:1632-1638, 1993 8. Krebs IW, Long-Marin SC, Childs JE: Causes, cost, and estimates of rabies postexposure prophylaxis treatment in the United States. Journal of Public Health Management and Practice 4:56-62, 1998 9. Krebs JW, Smith JS, Rupprecht CE, et al: Rabies surveillance in the United States during 1996. JAVMA 211:1525-1539,1997 10. National Association of State Public Health Veterinarians: Compendium of animal rabies control, 1998. MMWR Morb Mortal Wkly Rep 47(RR-9):1-9, 1998 11. National Research Council: Committee on Animal Health report: Rabies and its control. JAVMA 108:293-302, 1946 12. Rupprecht CE, Smith JS, Fekadu M, et al: The ascension of wildlife rabies: A cause for public health concern or intervention? Emerg Infect Dis 1:107-113, 1995 13. Rupprecht CE, Smith JS, Krebs J, et al: Current issues in rabies prevention in the United States, health dilemmas, public coffers, private interests. Public Health Rep 111:400-407, 1996 14. Texas Department of Health: Rabies Prevention in Texas 1997. Austin, TX, Texas Department of Public Health, stock no 6-108, 1997

Address reprint requests to M. Gayne Fearneyhough, BS, DVM 516 Lariat Lane Dripping Springs, TX 78620 e-mail: fearney®flash.net