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Update on rabies exposure and vaccine prophylaxis

Issue: July 2012

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Infection with rabies virus produces an acute illness with rapidly progressive central nervous system manifestations, including anxiety, dysphagia and seizures, which are almost invariably lethal. Despite the recent attention focused on rabies in some geographic areas, the number of cases detected in humans in the United States has steadily declined since 1950. An average of one or two cases has occurred annually since 1960. This decline reflects the widespread vaccination of domestic pets and the availability of effective immunoprophylaxis after exposure to a rabid animal.

Most of the United States is an endemic area for rabies. Raccoons, skunks, foxes, coyotes and bats are common vectors. However, any warm-blooded wild or domestic carnivore can transmit the virus. Exempt are rabbits and most small rodents, including squirrels and mice. When infected experimentally with rabies, most rodents do not shed the virus in their saliva. Although unusual, transmission has been documented to occur from “house pets,” including dogs, cats and ferrets. Local health authorities should be consulted when there is doubt about the local rabies status of a particular species of biting animal.

M. Douglas Baker

Despite the large focus of rabies in raccoons in the eastern United States, human cases attributed to the raccoon rabies virus variant are infrequent. However, case reports involving domestic cats and dogs have re-emerged coincident with the surge within the raccoon population during the past 30 years. Of the 42 cases of rabies in humans diagnosed in the United States from 1980 to 1997, 13 were related to rabid animals outside of the United States. From 2000 to 2004, 15 human cases of domestically acquired rabies were reported in the United States. Antigenic and genetic analysis determined that 14 were infected with bat-associated strains, and one with a raccoon strain.

Pathophysiology

Rabies virus is an RNA virus classified in the Rhabdoviridae family. It is concentrated in animal saliva. Most cases occur after introduction of the virus into an open wound. Another, but much less common, method of infection is direct mucosal exposure. It is also conjectured that exposure to high concentrations of airborne virus (as might occur in a cave that is densely inhabited by bats) can result in infection; however, there have been no confirmed cases of transmission to humans by that route. Transmission has also rarely occurred in the laboratory (airborne) and by transplantation of corneas from patients dying of undiagnosed rabies. Person-to-person transmission by bites has not been documented, although the virus has been isolated from the saliva of patients.

Prevention

Many states or commonwealths require rabies vaccinations for “at-risk” pets (ie, pets that could possibly become exposed to rabies). That vaccine is generally required every 2 years for dogs and cats, and in some animals, the vaccine could be effective for more than 2 years. The longevity of effectiveness of the vaccine in humans is very variable.

The AAP Red Book lists current recommendations for administration of rabies vaccines. When a child presents with a complaint of “animal bite” from a mammal, the managing physician should attempt to determine the nature of the beast and its rabies status. If the biting animal is known to have up-to-date vaccination status, then the bitten child need not receive prophylactic vaccines. If the biting animal is a wild carnivore or woodchuck that is unavailable for examination, it should be regarded as rabid, and immunization of the bitten child should proceed (see below). If the biting animal is healthy and available (captive), but its vaccine status cannot be verified or is not up-to-date, the following steps should be taken.

Biting Mammal (healthy and captive):

• can be sacrificed and the brain inspected for rabies, or
• can be quarantined (10 days) and observed for suspicious behavior.

Bitten Child:

• can be administered rabies prophylaxis (see below), or
• can await administration of rabies prophylaxis, pending (a) or (b) above.

Rabies prophylaxis requires administration of two agents. Rabies immune globulin (RIG) provides temporary passive immunization, whereas other agents (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]) produce a longer-acting (active) protection from the virus. The development of newer vaccines has markedly reduced the incidence of reactions previously associated with post-exposure prophylaxis with duck embryo vaccine.

Passive immunization is accomplished by administering RIG only once, on the day of initial presentation, at a dose of 20 IU/kg. The single exception is the person who has been immunized previously with rabies vaccine and has a documented adequate rabies antibody titer. The CDC currently recommends that the entire dose of RIG should be infiltrated into the soft tissues surrounding the bite site. If that is impractical, the amount unable to be infiltrated (traditionally) has been injected into a large muscle distant from the injection site for the active vaccine (eg, gluteus or quadriceps on the opposite side of the body).

Active immunization is accomplished by administering either of two equally effective vaccines, HDCV or PCECV, in multiple separate doses. Regardless of the child’s weight or age, the dose is 1 mL, injected into the deltoid muscle. Single doses are intended to be administered on days 0, 3, 7 and 14. Day 0 is the day of initial presentation. Before 2010, a fifth dose was also recommended to be administered on day 28.

However, recent experience indicates that four vaccine doses in combination with RIG produce adequate immune responses. With HDCV administration, there is a 6% incidence of serum sickness-like (type III) hypersensitivity reactions to booster doses given months or years after the primary series. PCECV can be used in patients who develop such sensitivity. All brands are expensive. The charge to the patient for the active vaccine alone (four doses) is several thousand dollars. To be effective, all four doses must be given. If there is any patient-related deviation from the schedule, the manufacturer should be contacted for advice about the proper method of completion. The toll-free number is printed on the vaccine container.

Bat exposure

Bat exposures deserve a special footnote. Between 1980 and 2000, 26 of 42 rabies cases diagnosed in the United States were bat variants. Of the 14 domestically acquired human cases of bat variant rabies documented from 2000 to 2004, 10 had presumed direct contact with bats (four were transplant recipients of infected tissue). Only three of the 10 had a known history of a bat bite.

Because the caliber of bat teeth is very small, their bites can be imperceptible, both in terms of noticeable pain and visible evidence on the skin. If anyone believes that they could have been bitten by a bat (including physical contact without a perceived bite), regardless of the findings on physical examination, rabies prophylaxis should be provided.

Rabies prophylaxis should also be administered to anyone who has an open wound or mucous membrane that could have become contaminated with saliva or other potentially infectious material, or who has occupied the same closed space with a bat during a time of altered perception (eg, asleep, intoxicated, developmentally immature, mentally impaired), regardless of the findings on physical examination.

All animal bites are supposed to be reported to the local animal warden. Animal shelters are often capable of quarantining the biting animal. The police generally need not be contacted, unless no one is available at the local animal shelter, and the animal needs to be located for quarantine or sacrifice.

• M. Douglas Baker, MD, is director of emergency medicine and vice president for community outreach at Johns Hopkins Children’s Center. He is also a member of the Infectious Diseases in Children Editorial Board. Disclosure: Dr. Baker reports no relevant financial disclosures.