5 Jun

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.

Adverse Effects

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.

Special Considerations

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).

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