Rabies is a zoonotic virus transmitted to humans by bite, scratch, or vaporization to mucous membranes. Other terres- trial mammals are vectors. Once infection occurs, a series of progressive neoneuronal symptoms occur, such as nausea and vomiting, abdominal pain, headaches, photophobia, etc. These tend to progress to more serious symptoms involving muscle weaknesses, slurred speech, muchal rigidity, copious oral secretions, and agitation. Fever may vary by case from low grade to high (e.g., 104ºF). Progressive encephalopathy ensues with coma preceding death.
Rabies continued to be a feared disease for centuries, even after Louis Pasteur developed the ﬁrst vaccine (1885) for post-exposure treatment of rabies (163). This and several other rabies vaccines that followed contained brain or nerve tissue, which posed a serious risk of neurological complica- tions. In addition, some of these vaccines led to pathogenic infections because of imperfect inactivation of the vaccine virus. Safer duck embryo vaccines were later introduced, but proved to be less immunogenic. After years of development and studies, the cell culture-derived vaccines have become the “gold standard” for rabies immunization. The human diploid cell vaccine (HDCV) was licensed in the United States in 1980, and contains concentrated and puriﬁed inactivated rabies virus from the Pitman-Moore strain.
When compared with brain tissue vaccine and duck embryo vaccine, human diploid cell cultures are superior, as they express: 1) high antigenicity; 2) rapid development of antibodies; and 3) absence of adverse reactions, even in later- administered booster inoculation (164).
Worldwide, greater than 95% of the 50,000 cases of human rabies occur annually as a result of accidental expo- sure to rabid bats. In the United States, domestic animals that were exposed to stray or wild animals were once the main cause of rabies infection. Rabies control through pet vaccination and
removal of stray or unwanted animals reduced conﬁrmed cases of rabies in dogs from nearly 7,000 in 1947 to 89 in 2001. Rabies vaccines are currently approved for dogs, cats, sheep, cattle, horses, and ferrets (165). In additional, reduced han- dling of wildlife, non-removal of wildlife to a domestic setting, pet vaccination, use of oral rabies vaccine for coyotes and grey foxes distributed aerially, and prompt treatment of wounds have signiﬁcantly reduced human rabies. Of concern are those species that appear to act as a latent reservoir for the host; skunks, raccoons, and bats are prime examples (166). Of the U.S. rabies cases reported for 2002, several commonalities exist. Primarily, the patient did not report contact with a non- domestic animal and the possibility or actual exposure to a rabid animal. Only after the neurological events were irre- versible did acquaintances relate some contact with an animal that could have had rabies. These are highlighted in Table 4.4.
In several clinical studies of the rabies vaccine regimens for pre- and postexposure prophylaxis, all subjects developed antibody responses within 2–4 weeks (167–169). The antibody response typically develops in 7–10 days and lasts for at least 2 years (170). Preexposure prophylaxis is intended for those at high risk of contracting rabies (bites by carnivorous wild ani- mals or bats; bites by dogs or cats that develop symptoms dur- ing 10 days of observation, or are rabid, suspected rabid, or unknown (i.e., escaped); or any bite from an unprovoked attack), and is given in three doses on days 0, 7, and 21 or 28. Postexposure prophylaxis is given to those who are exposed to suspected or conﬁrmed rabid animals, according to recommen- dations by the CDC (170). This regimen is given in conjunction with rabies immune globulin and consists of 5 vaccinations given on days 0, 3, 7, 14, and 28. Previously immunized indi- viduals who have been exposed to rabid animals require only vaccination given in 2 doses 3 days apart.
For each of the currently utilized vaccines approved for use worldwide, adverse events differ. Vaccines are listed in order of efﬁcacy and safety with the most safe vaccine listed ﬁrst. HDCV and RVA are interchangeable when used as recommended.
HDCV (Human Diploid Cell Vaccine)
Nausea, abdominal pain, headache, dizziness, and muscle aches. Reported by 20% of recipients (171). Allergic reaction. Urticaria or anaphylactic shock are
rarely reported (172).
Neurological complication. Rarely reported, although there have been three cases of Guillain-Barré syndrome reported (170).
Booster shots of HDCV. May cause an immune com- plex-like reaction within 2–21 days after vaccination. Reactions may include generalized urticaria, angioede- ma, nausea, vomiting, fever, malaise, arthralgia, or ar- thritis (173,174).
RVA (Rabies Vaccine Absorbed)
Anaphylactic reaction. Has not been reported among users.
Local reaction. Occurs in 65–70% of patients, with 10%
reporting mild symptoms.
Immune complex-like illness. Rare (<1%).
Serious neurological condition. Rare.
PCECV (Puriﬁed Chick-Embryo Cell-Culture Vaccine)
Anaphylactic shock. Two cases of anaphylaxis have oc- curred among 11.8 million doses worldwide.
Egg allergy. Reaction is a concern for those with egg al- lergies.
Local and mild systemic reaction. Occurs the least in PCECV. No immune complex-like illnesses have been reported.
Brain or Nerve Tissue
Neurological complication. Serious risk of neurologi- cal complications.
Pathogenic infection. Caused by imperfect inactiva- tion of vaccine virus.
Immunosuppressive agents. Corticosteroids and oth- er immunosuppressive agents may suppress antibody development following vaccinations. Unless they are absolutely necessary, these should not be administered during postexposure therapy.
Antimalarials. Chloroquine phosphate, meﬂoquine, and other antimalarials can diminish response to rabies treatment. Intramuscular injection of the vaccine en- hances response in those taking antimalarials.
Immunosuppressed patients. In patients preparing to undergo transplants or chemotherapy, or who have im- munosuppressive diseases, some physicians have rec- ommended doubling the dose of rabies vaccine to achieve an acceptable immune response (175–177).