Special Medical Reports

CDC Issues Revised Guidelines for the Prevention of Human Rabies

Am Fam Physician. 1999 Apr 1;59(7):2007-2014.

The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) has revised its recommendations for the prevention of human rabies in the United States. The previous recommendations on rabies prevention were published in 1991. The revised guidelines, published in the January 8, 1999, issue of the reports and recommendations series of Morbidity and Mortality Weekly Report (MMWR), offer new information about a vaccine approved in 1997, exposure to bats, an observation period for domestic ferrets and changes in the local administration of rabies immune globulin.

The complete contents of the guidelines cover rabies biologics (vaccines and immune globulin), primary or preexposure vaccination, postexposure prophylaxis (rationale for treatment, treatment of wounds, immunization, and treatment outside the United States), vaccination and serologic testing, management of adverse reactions, and precautions and contraindications (immunosuppression, pregnancy and allergies). The MMWR report also provides continuing medical education activity sponsored by the CDC.

Paul M. Arguin, M.D., in the Division of Viral and Rickettsial Diseases at the National Center for Infectious Diseases, prepared the report for MMWR. Richard Zimmerman, M.D., M.P.H., Pittsburgh, Pa., is the liaison representative to ACIP from the American Academy of Family Physicians.

The following information has been excerpted from the document.

Introduction

Rabies in humans is rare in the United States, but the CDC estimates that as many as 39,000 persons receive postexposure prophylaxis annually. The risk of infection must be carefully evaluated by the clinician in the management of potential human rabies exposures. The CDC considers administration of postexposure prophylaxis to be a medical urgency, not a medical emergency, although ACIP emphasizes that decisions about using prophylaxis should not be put off.

Rabies Biologics

Two types of rabies immunizing products are available. These include rabies vaccines that induce an active immune response, including the production of neutralizing antibodies lasting for two years or more, and rabies immune globulin that provides a rapid, passive immunity for only a short time.

Four formulations of three inactivated rabies vaccines are approved for preexposure and postexposure prophylaxis in the United States. Human diploid cell vaccine is available in both a form for intramuscular administration (Imovax Rabies) and a form for intradermal administration (Imovax Rabies I.D.). Rabies vaccine adsorbed (Rabies Vaccine Adsorbed) is approved for intramuscular administration only. The newest, purified chick embryo cell vaccine (RabAvert) became available in 1997. It is prepared from the fixed rabies virus strain Flury LEP grown in primary cultures of chicken fibroblasts. The virus is inactivated with betapropiolactone and further processed by zonal centrifugation in a sucrose density gradient. It is formulated for intramuscular administration only. All three types of vaccines are considered equally safe and effective by ACIP.

Two rabies immune globulin products (BayRab and Imogam) are available. Both products are considered equally effective when used as directed. In previously unvaccinated persons who have been exposed to rabies, rabies immune globulin is administered only once to provide immediate antibodies until the patient responds to the vaccine.

Preexposure Prophylaxis

Preexposure prophylaxis does not eliminate the need for additional therapy after a rabies exposure, but it simplifies treatment. It also may provide protection to persons at risk for inapparent exposure to rabies. All persons who belong to high-risk groups for exposure to rabies should be offered preexposure prophylaxis (see Table 1). These groups include veterinarians, animal handlers, certain laboratory workers, and those persons whose activities bring them into frequent contact with rabies virus or potentially rabid bats, raccoons, skunks, cats, dogs or other animals. Some persons who will be traveling internationally may need preexposure prophylaxis if they will be in areas where they might come in contact with animals.

TABLE 1

Rabies Preexposure Prophylaxis Guide—United States 1999

Risk category Nature of risk Typical populations Preexposure recommendations

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 six months; booster vaccination if antibody titer is below acceptable level.†

Frequent

Exposure usually episodic, with source recognized, but exposure also might be unrecognized. Bite, nonbite or aerosol exposure.

Rabies diagnostic laboratory workers,* spelunkers, veterinarians and staff, and animal-control and wildlife workers in rabies-enzootic areas.

Primary course. Serologic testing every two years; booster vaccination if antibody titer is below acceptable level.†

Infrequent (greater than population at large)

Exposure nearly always episodic with source recognized. Bite or nonbite exposure.

Veterinarians and animal-control and wildlife workers in areas with low rabies rates. Veterinary students. 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 (population at large)

Exposure always episodic with source recognized. Bite or nonbite exposure.

U.S. population at large, including persons in rabies-epizootic areas.

No vaccination necessary.


*—Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor.

†—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 the titer falls below this level.

From the Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999; Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-1):6.

TABLE 1   Rabies Preexposure Prophylaxis Guide—United States 1999

View Table

TABLE 1

Rabies Preexposure Prophylaxis Guide—United States 1999

Risk category Nature of risk Typical populations Preexposure recommendations

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 six months; booster vaccination if antibody titer is below acceptable level.†

Frequent

Exposure usually episodic, with source recognized, but exposure also might be unrecognized. Bite, nonbite or aerosol exposure.

Rabies diagnostic laboratory workers,* spelunkers, veterinarians and staff, and animal-control and wildlife workers in rabies-enzootic areas.

Primary course. Serologic testing every two years; booster vaccination if antibody titer is below acceptable level.†

Infrequent (greater than population at large)

Exposure nearly always episodic with source recognized. Bite or nonbite exposure.

Veterinarians and animal-control and wildlife workers in areas with low rabies rates. Veterinary students. 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 (population at large)

Exposure always episodic with source recognized. Bite or nonbite exposure.

U.S. population at large, including persons in rabies-epizootic areas.

No vaccination necessary.


*—Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor.

†—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 the titer falls below this level.

From the Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999; Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-1):6.

Postexposure Prophylaxis

Every person who has a possible exposure to rabies should be evaluated by a physician. Consultation with local or state public health officials about the need for prophylaxis may be necessary. Factors such as type of exposure, circumstances of exposure, bite and nonbite exposure should be considered before postexposure prophylaxis is started (see Table 2).

TABLE 2

Rabies Postexposure Prophylaxis Guide—United States, 1999

Animal type Evaluation and disposition of animal Postexposure prophylaxis recommendations

Dogs, cats and ferrets

Healthy and available for 10 days of observation.

Persons should not begin prophylaxis unless animal develops clinical signs of rabies.*

Rabid or suspected rabid.

Immediately vaccinate.

Unknown (e.g., escaped).

Consult public health officials.

Skunks, raccoons, foxes and most other carnivores; bats

Regarded as rabid unless animal proved negative by laboratory tests.†

Consider immediate vaccination.

Livestock, small rodents, lagomorphs (rabbits and hares), large rodents (woodchucks and beavers), and other mammals

Consider individually.

Consult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits and hares almost never require antirabies postexposure prophylaxis.


*—During the 10-day observation period, begin postexposure prophylaxis at the first sign of rabies in a dog, cat or ferret that has bitten someone. If the animal exhibits clinical signs of rabies, it should be euthanized immediately and tested.

†—The 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.

From the Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999; Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-1):7.

TABLE 2   Rabies Postexposure Prophylaxis Guide—United States, 1999

View Table

TABLE 2

Rabies Postexposure Prophylaxis Guide—United States, 1999

Animal type Evaluation and disposition of animal Postexposure prophylaxis recommendations

Dogs, cats and ferrets

Healthy and available for 10 days of observation.

Persons should not begin prophylaxis unless animal develops clinical signs of rabies.*

Rabid or suspected rabid.

Immediately vaccinate.

Unknown (e.g., escaped).

Consult public health officials.

Skunks, raccoons, foxes and most other carnivores; bats

Regarded as rabid unless animal proved negative by laboratory tests.†

Consider immediate vaccination.

Livestock, small rodents, lagomorphs (rabbits and hares), large rodents (woodchucks and beavers), and other mammals

Consider individually.

Consult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits and hares almost never require antirabies postexposure prophylaxis.


*—During the 10-day observation period, begin postexposure prophylaxis at the first sign of rabies in a dog, cat or ferret that has bitten someone. If the animal exhibits clinical signs of rabies, it should be euthanized immediately and tested.

†—The 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.

From the Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999; Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-1):7.

Since 1980, more than 50 percent of human cases of rabies reported to the CDC have been associated with bats. Recent data suggest that bats can transfer the rabies virus through minor or even unrecognized bites. The limited injury inflicted by a bat bite makes it difficult for health care professionals to determine the risk of rabies resulting from an encounter with a bat. Postexposure prophylaxis might be appropriate even if a bite, scratch or mucous membrane exposure is not apparent, if it is possible that such an exposure occurred.

Treatment

Components of rabies postexposure prophylaxis are wound treatment and, in previously unvaccinated persons, the administration of both rabies immune globulin and vaccine (see Table 3). Postexposure prophylaxis should begin immediately for persons who have been bitten by animals proved to be rabid. Studies have shown that a regimen of one dose of rabies immune globulin and five doses of human diploid cell vaccine over a 28-day period is safe and effective. The other two available vaccines have been shown to have equal efficacy with human diploid cell vaccine.

TABLE 3

Rabies Postexposure Prophylaxis Schedule—United States, 1999

Vaccination status Treatment Regimen*

Not previously vaccinated

Wound cleansing

All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as a povidone-iodine solution should be used to irrigate the wounds.

RIG

Administer 20 IU per kg body weight. If anatomically feasible, the full dose should be infiltrated around the wound(s) and any remaining volume should be administered intramuscularly at an anatomic site distant from vaccine administration. Also, RIG should not be administered in the same syringe as vaccine. Because RIG might partially suppress active production of antibody, no more than the recommended dose should be given.

Vaccine

HDCV, RVA or PCEC, 1.0 mL intramuscularly (deltoid area†), one each on days 0,‡ 3, 7, 14 and 28.

Previously vaccinated§

Wound cleansing

All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as a povidone-iodine solution should be used to irrigate the wounds.

RIG

RIG should not be administered.

Vaccine

HDCV, RVA or PCEC, 1.0 mL intramuscularly (deltoid area†), one each on days 0‡ and 3.


HDCV = human diploid cell vaccine; PCEC = purified chick embryo cell vaccine; RIG = rabies immune globulin; RVA = rabies vaccine adsorbed.

*—These regimens are applicable for all age groups, including children.

†—The 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.

‡—Day 0 is the day the first dose of vaccine is administered.

§—Any person with a history of preexposure vaccination with HDCV, RVA or PCEC; prior postexposure prophylaxis with HDCV, RVA or PCEC; or previous vaccination with any other type of rabies vaccine and a documented history of antibody response to the prior vaccination.

From the Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-1):12.

TABLE 3   Rabies Postexposure Prophylaxis Schedule—United States, 1999

View Table

TABLE 3

Rabies Postexposure Prophylaxis Schedule—United States, 1999

Vaccination status Treatment Regimen*

Not previously vaccinated

Wound cleansing

All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as a povidone-iodine solution should be used to irrigate the wounds.

RIG

Administer 20 IU per kg body weight. If anatomically feasible, the full dose should be infiltrated around the wound(s) and any remaining volume should be administered intramuscularly at an anatomic site distant from vaccine administration. Also, RIG should not be administered in the same syringe as vaccine. Because RIG might partially suppress active production of antibody, no more than the recommended dose should be given.

Vaccine

HDCV, RVA or PCEC, 1.0 mL intramuscularly (deltoid area†), one each on days 0,‡ 3, 7, 14 and 28.

Previously vaccinated§

Wound cleansing

All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water. If available, a virucidal agent such as a povidone-iodine solution should be used to irrigate the wounds.

RIG

RIG should not be administered.

Vaccine

HDCV, RVA or PCEC, 1.0 mL intramuscularly (deltoid area†), one each on days 0‡ and 3.


HDCV = human diploid cell vaccine; PCEC = purified chick embryo cell vaccine; RIG = rabies immune globulin; RVA = rabies vaccine adsorbed.

*—These regimens are applicable for all age groups, including children.

†—The 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.

‡—Day 0 is the day the first dose of vaccine is administered.

§—Any person with a history of preexposure vaccination with HDCV, RVA or PCEC; prior postexposure prophylaxis with HDCV, RVA or PCEC; or previous vaccination with any other type of rabies vaccine and a documented history of antibody response to the prior vaccination.

From the Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999;48(RR-1):12.

The wound and scratches should be thoroughly washed with soap and water and a virucidal agent. In animals, thorough wound cleansing alone has been shown to reduce the likelihood of transmitting rabies. Tetanus prophylaxis and measures to control bacterial infection also should be given if needed. The need for suturing should be determined on an individual basis.

Rabies immune globulin is administered at the beginning of antirabies prophylaxis. If it is not given at that time, it can be administered through the seventh day after the administration of the first dose of vaccine. Beyond the seventh day, rabies immune globulin does not need to be given because vaccination with cell culture should have occurred. The recommended dose of human rabies immune globulin is 20 IU per kg body weight. If feasible, the full dose of rabies immune globulin should be thoroughly infiltrated in the area around and into the wounds. Any remaining volume should be given intramuscularly at a site distant from vaccine administration. It should never be administered in the same syringe as vaccine or in the same area as vaccine.

For vaccine use, the CDC recommends a regimen of five 1-mL doses of any one of the three approved vaccines. The first dose should be given as soon as possible. Additional doses should be given on days 3, 7, 14 and 28 after the first vaccination. The vaccination should always be given intramuscularly in the deltoid area for adults. For children, the anterolateral aspect of the thigh can also be used. The gluteal area should never be used because administration in this area results in lower neutralizing antibody titers.


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