Special Feature

Update: Rabies 1999

By Richard A. Harrigan, MD

The centers for disease control and prevention (CDC) has recently published an updated version of the recommendations of the Advisory Committee on Immunization Practices (ACIP) with regard to rabies.1 Last revised in 1991, this publication is the reference standard in this country for the current status of rabies and its prevention. Key points from this document for the practicing emergency physician (EP) will be highlighted below.

What are the epidemiologic trends for animal rabies?

The likelihood that a human will be exposed to a rabid domestic animal in the United States continues to decline over this half-century. During the 1990s, the number of reported cases of cat rabies generally exceeded that of dogs, a trend attributed to differences between the two species with regard to vaccination laws, leash laws, and roaming behaviors. As with wild animals, domestic animal rabies trends vary by locale (e.g., the United States-Mexico border region features an epizootic of dog rabies).

Wild animals most often infected with rabies include raccoons, skunks, foxes, bats, and coyotes, with raccoons being the most commonly reported wild animal to have the disease.2 It is the bat, however, that has been responsible for the most cases of human rabies since 1980; 21 (58%) of the 36 cases of human rabies diagnosed in this country during that time period have been traced to bats. Of these 21 cases, a bite was reported in only 1-2 cases; apparent contact without a detectable bite occurred in 10-12 cases; and in the remaining 7-10 cases, no exposure to a bat was reported (number of cases reported as a range due to conflicting report information). Small rodents (e.g., squirrels, chipmunks, rats, mice, and hamsters) are almost never found to be rabid, and have never been shown to transmit the virus. The same is true for lagamorphs, which include rabbits and hares. Woodchucks, although rodents, are at risk for rabies in certain areas of the country; indeed, they accounted for 93% of reported cases of rodent rabies in the first six years of this decade.

Animal rabies has been reported from all 49 continental states; only Hawaii remains free of rabies. Rabid bats have been reported from all states except Hawaii.

What constitutes a significant exposure with regard to rabies transmission?

The rabies virus is principally transmitted through contact with the saliva or neural tissue of the affected animal. Viral access to the victim is via a break in the skin or mucous membrane exposure. Thus, bites are the most common route of transmission; indeed, any break in the skin by teeth constitutes a bite. Theoretically, scratches also can lead to viral transmission. Petting a rabid animal or touching its blood, urine, or feces does not constitute an exposure. Other documented routes of transmission include exposure to large quantities of aerosolized virus, as has occurred in spelunkers (bat guano) and laboratory workers. There have been eight documented cases of human-to-human transmission via corneal transplant.

The numerous cases of human rabies contracted from bats are troubling, especially because, in the overwhelming majority of cases, no bat bite was known to have occurred. Although most of the epidemiologic data in these cases were retrospectively gathered, and, thus, a bat bite may have gone undetected, these data have led to a change in the recommendation for postexposure prophylaxis (PEP) procedures with regard to bats. Clear bat bites merit PEP, but treatment should also be instituted when direct contact or a bite cannot be ruled-out and the bat is not available for immediate sacrifice and testing. Examples of such situations include discovery of a bat in the same room with a sleeping person, a previously unattended child, a mentally disabled person, or an intoxicated person.

When should post-exposure prophylaxis be instituted, and when should it be withheld pending observation of animal behavior?

Initiation of PEP is dependent upon the source animal species and the determination of whether there was a true exposure, as outlined above. Bites or significant exposures from high-risk wild animals merit initiation of PEP pending sacrifice and testing of the animal (in coordination with local health department authorities). If the animal tests negative for rabies, PEP can be discontinued. If the animal is unavailable for testing or tests positive, PEP must be completed. All wild terrestrial carnivores are at risk for rabies, but the highest risk animals include raccoons, skunks, foxes, coyotes, and any other animal exhibiting bizarre or aggressive behavior (unprovoked attacks). That being said, signs of rabies are notoriously unreliable among wild animals; any significant exposure should lead to prompt sacrifice and testing of the source animal. For example, an overly-friendly armadillo that was adopted by a young girl was ultimately found to be rabid.3 Once again, rodents (with the exception of woodchucks in some regions of the United States) and lagamorphs are extremely low-risk; their behavior should be reviewed on a case-by-case basis, and decisions to treat can be made in conjunction with local health authorities. Rat bites, something we see not infrequently in North Philadelphia, are an example of wild animal exposures not at risk for rabies; an analagous example would be a bite by a chipmunk being fed nuts in a park (provoked and low-risk source animal).

Among domestic animals, PEP may be withheld pending 10-day observation of the source animal—if it is a healthy dog, cat, or ferret. Previously, this was true only for dogs and cats, but now the rabies viral shedding pattern for ferrets is also well-understood. Should the animal become ill during that observation/confinement period, a veterinary evaluation should promptly ensue in conjunction with notification of the local health authorities. Euthanasia and laboratory analysis of the brain will follow should the animal show signs suggestive of rabies, and decision to treat will be based on the outcome. Stray or unwanted dogs or cats should either be observed for the 10-day period or sacrificed immediately and tested for rabies. If the source animal is unavailable for testing, then the likelihood of rabies should be weighed in light of regional trends for that species. In Philadelphia, if the source animal is a stray dog or cat unavailable for testing, the recommendation is to initiate PEP; the raccoon rabies epizootic in the Eastern United States principally is responsible for this.

Research has revealed the incubation period for rabies in humans is variable and may be prolonged—the average is 30-90 days,4 but incubation periods of greater than one year have been reported. Thus, initiation of PEP is indicated regardless of time expired since the exposure event, if the encounter meets criteria with regard to exposure type and source animal species and the patient is not already showing clinical signs of rabies.

What are the components of post-exposure rabies prophylaxis?

There are two essential components to PEP: wound care and immunization. Wound care must include immediate and meticulous cleansing of the wound with water, soap, and a virucidal agent (e.g., providone-iodine). Immunization procedures depend upon the immunization status of the patient. Most patients have not been previously immunized, so they will require both passive and active immunization. Rabies immune globulin (RIG) provides antibodies to the victim, and should be administered at the first encounter, once the decision to treat has been made. Previously, the dose (20 IU/kg) was divided (50% to the wound site[s], and 50% to the gluteal region). Current recommendations require that as much of the full dose as is anatomically possible should be infiltrated at the wound site(s), and the remainder (if any) should then be given IM at a site distal to the injection site for the vaccine. Two equally efficacious RIG preparations are available in the United States: Imogam and BayRab. The recommended dose should not be exceeded, as RIG can interfere with the active antibody response induced by the vaccine.

Vaccine is given in a five-part series on days 0 (the initial encounter, in most cases), 3, 7, 14, and 28. The recommended site is the deltoid in the adult, and the anterolateral thigh in the small child—never in the gluteus, due to reports of vaccine failure in the past. Three equivalent vaccines are now available in the United States: human diploid cell vaccine (HDCV or Imovax), rabies vaccine adsorbed (RVA), and purified chick embryo cell vaccine (PCEC or RabAvert). The dose and route (1 cc IM) are the same for all three.

Both immune globulin and vaccine are safe in pregnancy. Immunocompromised patients must have serum antibody titers checked during follow-up to ensure immunity.

How is post-exposure prophylaxis modified if the victim has been previously immunized against rabies?

If the patient has had pre-exposure prophylaxis with an appropriate cell culture vaccine (e.g., veterinarian, spelunker, animal handler), or has previously received PEP for another incident, then only wound care and vaccine are needed. RIG is contraindicated, as it may interfere with the anamnestic immune response to the vaccine. Regardless of pre-booster antibody titers, these patients only require vaccine on days 0 and 3.

Conclusions

A working knowledge of rabies evaluation and prophylactic treatment procedures is essential to the EP. Such treatment is urgent, and though not emergent, should be initiated in the ED, given that the exposure meets the treatment criteria outlined above. While wildlife exposures are the most common source in the United States, an awareness of current epidemiologic trends and regional health department recommendations is important when deciding if the source animal is at risk for harboring or transmitting the virus. Strict adherence to wound care and immunization guidelines will prevent the patient from developing rabies. The 1999 revision of the ACIP guidelines provides a thorough discussion of antirabies biologics, vaccination procedures (pre- and postexposure), adverse reactions, and follow-up considerations. The essential points for the EP have been outlined above, including a discussion of the revisions of the 1991 recommendations. These revisions include more liberal treatment of bat exposures, the change in RIG administration guidelines, availability of alternative antirabies biologics, and the extension of the 10-day observation and confinement option to healthy, domestic ferrets.

References

1. Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb Mortal Wkly Rep MMWR 1999;48(RR 1):1-21.

2. Krebs JW, et al. Rabies surveillance in the United States during 1996. J Am Vet Med Assoc 1997;211: 1525-1539.

3. Leffingwell LM, Neill Su. Naturally acquired rabies in an armadillo (Dasypus novemcintus) in Texas. J Clin Microbiol 1989;27:174-175.

4. Warrell D. The clinical picture of rabies in man. Trans Roy Soc Trop Med Hyg 1976;70:188-195.