In the late 1800s, Pasteur, noting the long incubation period of rabies, suggested that a vaccine to induce an immune response before the development of disease might be useful in prevention. He apparently successfully vaccinated Joseph Meister, a boy severely bitten and exposed to rabies, with multiple injections of a crude vaccine made from dried spinal cord of rabies-infected rabbits. This treatment emerged as one of the best-known and most noteworthy accomplishments in the annals of medicine. It is now believed that vaccination induces antibody that is either neutralizing or inhibits cell-to-cell spread of virus. Natural infection does not lead to an early immune response and limitation of viral migration, because the virus is replicating in muscle or neural tissue and lymphocytes do not access these sites. Cytotoxic T lymphocytes are also induced by vaccine and appear to be directed against an antigen of the virus.
Vaccine-induced antibody inhibits viral spread
Currently, the prevention of rabies is divided into preexposure and postexposure prophylaxis. There are currently two inactivated (killed) vaccines licensed in the United States: human diploid cell vaccine (an attenuated strain of rabies virus grown in human diploid cell culture and inactivated by β-propiolactone) and purified chick embryo cell vaccine (fixed rabies virus strain grown in primary cultures of chicken fibroblasts and inactivated by β-propiolactone). Preexposure prophylaxis is recommended for individuals with high risk of contact with rabies virus, such as veterinarians, spelunkers, laboratory workers, and animal handlers. Preexposure prophylaxis consists of three doses of intramuscular injections (deltoid area) of vaccine on Days 0, 3, and 21 or 28. A booster dose is needed to maintain a neutralizing antibody titer of 1:5 in high-risk people (researchers working with rabies vaccine, veterinarians) after testing at 6 months later.
High-risk individuals include veterinarians, spelunkers, laboratory workers, and animal handlers
Postexposure prophylaxis requires careful evaluation and judgment. Every year, more than 1 million people are bitten by animals in the United States, and approximately 25 000 receive postexposure rabies prophylaxis. Worldwide, more than 15 million people receive rabies vaccine after rabid animal bites (postexposure) that prevent thousands of death annually worldwide. The physician must consider (1) whether the individual came into physical contact with saliva or another substance likely to contain rabies virus; (2) whether there was significant wound or abrasion; (3) whether rabies is known or suspected in the animal species and area associated with the exposure; (4) whether the bite was provoked or unprovoked (ie, the circumstances surrounding the exposure); and (5) whether the animal is available for laboratory examination.
Any wild animal or ill, unvaccinated, or stray domestic animal involved in a possible rabies exposure, such as an unprovoked bite, should be captured and killed. The head should be sent immediately to an appropriate laboratory, usually at the state health department, to search for rabies antigen by immunofluorescence. If examination of the brain by this technique is negative for rabies virus, it can be assumed that the saliva contains no virus and that the exposed person requires no treatment. If the test is positive, the patient should be given postexposure prophylaxis. It should be noted that rodents and rabbits are not important vectors of rabies virus. There have been no rabies deaths in the United States when postexposure prophylaxis was given promptly after exposure.
Careful history and studies of biting animal are important in decision making
Postexposure prophylaxis is based on immediate, thorough washing of the wound with soap and water (to kill the virus around the wound); passive immunization with antirabies hyperimmune globulin, including a portion instilled around the wound site (to neutralize the virus); and active immunization with antirabies vaccine on Days 0, 3, 7, and 14. For individuals who were previously immunized, the postexposure prophylaxis includes would cleansing with soap and water and rabies vaccination on Days 0 and 3 (hyperimmune globulin should not be given). Physicians should always seek the advice of the local health department when the question of rabies prophylaxis arises.
Rabies immune globulin plus vaccine necessary in postexposure management