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By Mary Louise Scully, MD
An excellent update on rabies was provided by Charles E. Rupprecht, the Rabies Section Chief of the CDC, during the Symposium, Control of Zoonoses: A Veterinary Perspective at the recent 51st annual ASTMH meeting in Denver, Colo. The most significant development is that Imovax-ID, the human diploid cell vaccine formulated for pre-exposure intradermal rabies vaccination, is no longer available in the United States. This event occurred in April 2001. The WHO position will remain supportive of the intradermal route for pre-exposure vaccination.
This discontinuation occurs in the setting of otherwise continued expansion of the intradermal route for pre-exposure prophylaxis and postexposure treatment, especially in areas of the world where rabies remains a significant health problem and cell-derived vaccines and rabies immune globulin are in short supply. It is thought that the estimated 50,000 rabies deaths reported per year (India alone reports 30,000 deaths per year) is actually an underestimate.1 For health care providers in the United States, the discontinuation of Imovax-ID eliminates a less-expensive pre-exposure rabies prophylaxis regimen. However, the human diploid cell vaccine Imovax-IM, rabies vaccine adsorbed (RVA), and purified chick embryo cell vaccine (PCEC) remain available in the United States for intramuscular use.
Rabies is an acute, fatal encephalitis caused by neurotropic RNA viruses in the family Rhabdoviridae, genus lyssavirus. Classic rabies virus (genotype 1) is the type species of lyssavirus. Only 1 viral species was believed to cause rabies, but more recent investigations have showed at least 7 putative genotypes. Classic rabies virus accounts for most cases of rabies, but all lyssaviruses have shown capacity as human or animal pathogens.
Although many carnivorous mammals can serve as hosts, dogs remain the major reservoir and vector of rabies virus. Worldwide, dogs cause the majority of the human deaths due to rabies. Although domestic and wild cats do not seem to act as reservoirs for rabies, cats are effective vectors of transmission; hence, cats should be vaccinated despite the small relative risk of sarcoma.
In the United States, adequate canine and livestock vaccination has largely eliminated rabies from domestic animals, and the majority of animal rabies occurs in wild terrestrial animals such as raccoons, which accounted for 37.7% of all animal rabies cases in 2000. Skunks, foxes, and other mammals, including mongooses, groundhogs, bobcats, coyotes, badgers, and opossums, accounted for the remainder. Small mammals and rodents such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, rabbits, and hares are not important in the epidemiology of rabies, and bites from these animals rarely require rabies prophylaxis.
Bats account for a relatively small proportion of the animal rabies cases reported in the United States (16.8% in 2000), but in the last 20 years variants of bat rabies have become the most common causes of human death from rabies.2 Six of the 7 lyssavirus genotypes have been isolated from bats. Of the 39 cases of bat-associated rabies deaths in the United States during the last 50 years, only 9 (23%) reported a definite history of a bite, even though 20 (51%) reported contact with bats.3 Since bats have small teeth, their bites might have gone unnoticed. Therefore, bat encounters in which a patient awakens to find a bat in the room, finding a bat in the room of an unattended child, or seeing a bat near a mentally impaired or intoxicated person warrant postexposure rabies prophylaxis.4
The resurgence of raccoon rabies that began in the Mid-Atlantic states in the late 1970s has spread so that raccoon rabies is now enzootic in all of the eastern coastal states as well as Alabama, Pennsylvania, Vermont, and West Virginia. Oral rabies immunization of free-ranging wildlife using vaccine-laden baits has shown promise in Europe, and similar efforts are under way to limit the expansion of raccoon rabies in the United States. More than 2 million doses of an oral vaccinia-rabies glycoprotein (V-RG) bait vaccine have been distributed in Ohio alone in the last 2 years. Additional states are expected to implement V-RG in the future as well. The hope is to make an immune barrier spanning the country from the shores of Lake Erie in Ohio south to the Gulf of Mexico in Alabama, preventing further westward spread of raccoon rabies.5 Unfortunately, these types of control measures are less applicable to limiting bat rabies.
A practical question from the audience raised the issue of an allergic reaction in a patient after the third dose of a postexposure series. Rupprecht suggested trying another rabies vaccine formulation. The decision to continue the series should be based on the exposure history. A titer in the midst of the series should not be used to decide if the patient is protected. If a patient has had significant rabies exposure, every effort should be made to complete the recommended postexposure treatment.
Two recent companion reviews referenced above deserve special mention as outstanding papers on the past, present, and future of rabies.2,3
1. Rabies vaccines. WHO Weekly Epidemiological Record. 2002;77(14):109-119.
2. Hemachudha T, et al. Human rabies: A disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol. 2002;1:101-109.
3. Rupprecht CE, et al. Rabies re-examined. Lancet Infect Dis. 2002;2:337-353.
4. CDC. Human rabies prevention-United States, 1999: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1999;48(No.RR-1).
5. Krebs JW, et al. Rabies surveillance in the United States during 2000. J Am Vet Med Assoc. 2001;219: 1687-1699.
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