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
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.
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.
- can be administered rabies prophylaxis (see below), or
- can await administration of rabies prophylaxis, pending (a) or (b)
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
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 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.
For more information:
- A new rabies vaccine. Med Lett Drugs Ther. 1998; 40:64-65.
- American Academy of Pediatrics. Rabies. In: Pickering LK, ed. 2003 Red Book: Report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL; AAP; 2000; 514-521.
- Blanton JD. J Am Vet Med Assoc. 2009;235:676-689.
- CDC. MMWR. 1999;48(RR-1):1-21.
- CDC. MMWR. 2010;59(RR-2):1–9.
- Fishbein DB. Vaccine. 1993;11:1390-1394.
- Kauffman FH. Am J Emerg Med. 1986;4:525-531.
- Krebs J. J Am Vet Med Assoc. 2004;225:1837-1849.
- Messenger SL. Clin Infect Dis. 2002;35:738-747.
- Strassburg MA. Ann Emerg Med. 1985;10:193-197.
- Winkler W. J Infect Dis. 1972;126:565-569.
- 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.