Rabies Post-Exposure and Management of the Veterinary Patient: Persistent Problems, New Solutions?
Cathleen A. Hanlon, VMD, PHD; Charles E. Rupprecht, VMD, MS, PHD
All animals in the Unites States, with the exception of those residing in Hawaii, are at risk for rabies exposure, whether housed exclusively indoors or primarily outdoors. Pets housed exclusively indoors, such as many ferrets and some cats, are still at risk for exposure. The home may be invaded by a rabid animal, with the greatest risk being from rabid bats and lower but real risks from raccoons, skunks, and foxes, as well as possible escape of pets from the house. In view of these risks, the recommendation for maintaining current rabies vaccination of cats, dogs, and ferrets is appropriate (1). Bat rabies is found throughout the USA with the exception of Hawaii (2). In addition, rabies among terrestrial reservoirs such as raccoons, skunks, foxes, and coyotes, affects the majority of the eastern USA, North-central and South-central USA, California, and Texas. The canine rabies virus variant, historically present among dogs, has been virtually eliminated in the USA. Apparently due to this achievement, pet owners and other members of the public are often surprised when rabies is diagnosed among wildlife or domestic animals in their locality, whether it be their neighborhood park, backyard, or in their home.
When an unvaccinated pet is exposed to rabies, there are few options. The animal may be euthanized to prevent the possibility of the development of rabies. The animal may be quarantined for six months, after which the animal is not considered at risk for developing rabies from that potential exposure. If the animal had received one or more vaccinations previously but is outdated by months or more on its vaccination at the time of the exposure, the current recommendation is still a six-month quarantine or euthanasia in many jurisdictions. Objectively, administering one or more booster vaccinations would increase the probability that the animal's anamnestic immunity would overcome any potential infection, but complete protection is not assured. Administration of booster vaccinations to an animal not currently vaccinated may provide a false sense of security to the owner and others that the animal is "vaccinated." Moreover, in a rabies-naïve animal, vaccine alone may not provide protection against a lethal rabies virus exposure. Despite published evidence of lack of protection by vaccine only post-exposure treatment (3), at least two articles in a peer-reviewed journal supports this practice (4, 5). The committee of the National Association of State and Public Health Association that authors the Compendium on Animal Rabies Control questioned the risk associated with vaccine-only post-exposure prophylaxis (6).
One alternative to euthanasia or a six-month quarantine is a regimen mimicking human rabies post-exposure prophylaxis. This report describes a recently published study in the American Journal of Veterinary Research (3).
For example, dogs were sedated and inoculated in the right masseter muscle with a salivary gland homogenate from a naturally infected rabid dog. Six hours later (day 0), 5 dogs were treated by administration of 2 murine anti-rabies glycoprotein monoclonal antibodies (mAb) and commercial vaccine; 5 received mAb alone; 5 received purified, heat-treated, equine rabies immune globulin (PHT-ERIG) and vaccine; 5 received PHT-ERIG alone; 4 received vaccine alone; and 5 control dogs were not treated. The mAb or PHT-ERIG was administered at the site of rabies virus inoculation. Additional vaccine doses for groups mAb plus vaccine, PHT-ERIG plus vaccine, and vaccine alone were administered IM in the right hind limb on days 3, 7, 14, and 35.
All control dogs and dogs that only received vaccine, developed rabies. In the PHT-ERIG and vaccine group, 2 of 5 dogs were protected, whereas none were protected with PHT-ERIG alone. Use of mAb alone resulted in protection in 4 of 5 dogs. Administration of mAb in combination with vaccine provided protection in 5 of 5 dogs.
There are a number of rabies vaccines licensed for use in domestic animals in the USA. To obtain USDA licensure, the demonstration of protection by a potential rabies vaccine against lethal virus challenge is required. In addition, rabies vaccines may be useful for off-label application in other species housed in zoological collections and for other captive wild and exotic species. As with all vaccines, it must be understood that the risk of disease occurrence in the individual animal is lowered with immunization but may not be completely eliminated. In particular, a single administration of rabies vaccine need only provide 80% protection against rabies virus challenge for licensure. Animals that have been vaccinated two or more times in their lifetime, with no lapse in current vaccination status between the two, have a much lower likelihood of developing rabies upon exposure and animals that are currently vaccinated and appropriately boosted with a post-exposure dose of vaccine rarely develop rabies. At present, the purpose of domestic animal vaccination against rabies is limited to preexposure vaccination and booster vaccination of currently vaccinated dogs following an exposure. Although human post-exposure prophylaxis (PEP) for rabies-naïve individuals is highly efficacious, there is no licensed post-exposure regimen for naïve domestic animals. The effectiveness of at least two experimental protocols similar to human PEP has been demonstrated experimentally in dogs (3, 7). The limitation of this approach is the expense of human rabies immune globulin due to its worldwide shortage and lack of practical availability even for human use in developing countries (8, 9). However, potential alternatives exist in the form of murine or human monoclonal antibodies (10,11) and, as more recently described, rabies antibodies produced in transgenic plants (12). If this practical alternative is developed for the US domestic pet market, it may also applicable in areas where human RIG is unaffordable for human treatment.
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13. Ko K, Tekoah Y, Rudd PM, Harvey DJ, Dwek RA, Spitsin S, Hanlon CA, Rupprecht C, Dietzschold B, Golovkin M, Koprowski H. Function and glycosylation of plantderived antiviral monoclonal antibody. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):8013-8. Epub 2003 Jun 10.