For the past several decades, the majority of naturally acquired, indigenous human rabies cases in the United States have resulted from variants of rabies viruses associated with insectivorous bats (5). The lone human case reported in the United States during 2005 and two of the three human rabies cases in 2006 were attributed to bat exposures (6,8). During 2004, two of the eight human rabies cases resulted from bat exposures. However, one of the three human rabies cases diagnosed in 2006 was associated with a dog bite that occurred in the Philippines, where canine rabies is enzootic. Owners whose pets are brought in by Animal Protection are required to pay an impound fee associated with their licensed or unlicensed pet at time of pick-up. Because of changes in tax laws, in 2003, SAPL merged with the Animal Welfare Institute, bringing together two of the oldest and leading animal protection organizations in the United States. If legislators wanted to know more about issues pertaining to humane slaughter, leghold traps or endangered species, they contacted SAPL. The Animal Rights in China website was launched on 22 July 2006, and is the major portal for animal rights issues in China. In 2006, a total of 79 cases of rabies were reported in domestic dogs, none of which was attributed to enzootic dog-to-dog transmission, and three cases were reported in humans (6). The infectious sources of the 79 cases in dogs were wildlife reservoirs or dogs that were translocated from localities where canine rabies virus variants still circulate.
None of the 2006 human rabies cases was acquired from indigenous domestic animals (6). Thus, the likelihood of human exposure to a rabid domestic animal in the United States has decreased substantially. The proposed revised recommendations and a draft statement were presented to ACIP in October 2006. After deliberations, the recommenda tions were unanimously approved with minor modifications. When definitive research evidence was lacking, the recommendations incorporated expert opinion of the workgroup members. The rabies workgroup reviewed the previous ACIP recommendations on the prevention of human rabies and deliberated on the available evidence. Randomized trials or well-conducted cohort studies with untreated comparison groups would provide the best evidence of the direct effectiveness of rabies pre-exposure and postexposure prophylaxis to prevent rabies-associated death. Because controlled human trials cannot be performed, studies describing extensive field experience and immunogenicity studies from certain areas of the world were reviewed. Data regarding the immunogenicity of rabies biologics also were reviewed. As a result of improved canine vaccination programs and stray animal control, a marked decrease in domestic animal protection organization rabies cases in the United States occurred after World War II.
However, rabies cases have occurred among those who received rabies pre-exposure prophylaxis and did not receive rabies postexposure prophylaxis (23), indicating that pre-exposure prophylaxis in humans is not universally effective without postexposure prophylaxis. Virus neutralizing antibodies are believed to have a primary role in preventing rabies virus infection. However, studies describing final health outcomes among persons exposed to the rabies virus do exist, including studies using formulations of rabies biologics, timing of vaccine doses, and routes of administration that are not recommended for use in the United States. Because of the paucity of formal studies on the effectiveness of rabies pre-exposure vaccination in humans, the literature was searched for studies that reported clinical outcomes among animals that received pre-exposure rabies prophylaxis with cell culture rabies vaccine and were subsequently challenged with rabies virus. ACIP’s charter requires the committee to consider the costs and benefits of potential recommendations when they are deliberating recommendations for vaccine use in the United States. The Advisory Committee on Immunization Practices (ACIP) Rabies Workgroup first met in July 2005 to review previous ACIP recommendations on the prevention of human rabies (published in 1999) and to outline a plan for updating and revising the recommendations to provide clearer, more specific guidance for the administration of rabies pre-exposure and postexposure prophylaxis.
25) or complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test (RFFIT) (used by ACIP as an indicator of an adequate adaptive immune response) (26). The literature also was searched for evidence regarding the safety of the licensed rabies biologics available for use in the United States in both pre-exposure and postexposure situations. Rabies vaccines induce an active immune response that includes the production of virus neutralizing antibodies. Nonetheless, the ability of a vaccine to elicit rabies virus neutralizing antibodies in animals and humans and the demonstration of protection in animals is generally viewed as a reasonable surrogate of protection for inferential extension to humans (24). Although a definitive “protective” titer cannot be described for all hosts under all exposure scenarios, two working definitions of adequate rabies virus neutralizing antibody reference values have been developed to define an appropriate, intact adaptive host response to vaccination. However, antibody titers alone do not always directly correlate with absolute protection because of other important immunologic factors.