"During the past several months, we at CDC have been working hard to take steps to increase HPV vaccination coverage among 11-12 year olds, including actively communicating with clinicians and parents about the benefits and safety of this cance"...
Rabies is a viral infection transmitted in the saliva of infected mammals. Both dog and bat saliva exposures appear to be major contributors (see below) with or without apparent bites. The virus enters the central nervous system of the host, causing an encephalomyelitis that is fatal. After the marked decrease of rabies cases among domestic animals in the US in the 1940s and 1950s, indigenously acquired rabies among humans decreased substantially. 1, 2 In 1950, for example, 4, 979 cases of rabies were reported among dogs, and 18 cases were reported among humans. Between 1980 and 1997, 95 to 247 cases were reported each year among dogs, and on average only two human cases were reported each year in which rabies was attributable to variants of the virus associated with indigenous dogs. 1, 3 Thus, the likelihood of human exposure to a rabid domestic animal in the US has decreased greatly. However, during the same period, 12 cases of human rabies were attributed to variants of the rabies virus associated with dogs from outside the US. 1, 4, 5 Therefore, international travelers to areas where canine rabies is still endemic have an increased risk of exposure to rabies. 1
Rabies among wildlife – especially raccoons, skunks, and bats – has become more prevalent since the 1950s, accounting for > 85% of all reported cases of animal rabies every year since 1976. 1, 2 Rabies among wildlife occurs throughout the continental US; only Hawaii remains consistently rabies-free. Wildlife is the most important potential source of infection for both humans and domestic animals in the US. Since 1980, a total of 21 (58%) of the 36 human cases of rabies diagnosed in the US have been associated with bat variants. 1, 3, 6, 7 In most other countries – including most of Asia, Africa, and Latin America – dogs remain the major species with rabies and the most common source of rabies among humans. Twelve (33%) of the 36 human rabies deaths reported to Centers of Disease Control and Prevention (CDC) from 1980 through 1997 appear to have been related to rabid animals outside the US. 1, 3, 7
Although rabies among humans is rare in the US, every year approximately 16, 000 to 39, 000 persons receive postexposure prophylaxis. 1, 8 In order to manage potential human exposures to rabies appropriately, the risk of infection must be accurately assessed. Administration of rabies postexposure prophylaxis is a medical urgency, not a medical emergency, but decisions must not be delayed. Systemic prophylactic treatments occasionally are complicated by adverse reactions, but these reactions are rarely severe. 1, 9-13
Data on the safety, immunogenicity, and efficacy of active and passive rabies immunization have come from both human and animal studies. Although controlled human trials have not been performed, extensive field experience from many areas of the world indicates that postexposure prophylaxis combining local wound treatment, passive immunization, and vaccination is uniformly effective when appropriately applied. 1, 14-19
Although no postexposure vaccine failures have occurred in the US since cell culture vaccines have been routinely used, failures have occurred abroad when some deviation was made from the recommended postexposure treatment protocol or when less than the currently recommended amount of antirabies sera was administered. 1, 20-23 Specifically, patients who contracted rabies after postexposure prophylaxis did not have their wounds cleansed with soap and water, did not receive their rabies vaccine injections in the deltoid area (i. e. , vaccine was administered in the gluteal area), or did not receive Rabies Immune Globulin (RIG) around the wound site. 1
Rabies antibody provides passive protection when given immediately to individuals exposed to rabies virus. 24 In a clinical study, Rabies Immune Globulin (Human) [RIG(H)] of adequate potency25 was used in conjunction with Rabies Vaccine of duck embryo origin. 25, 26 When a Rabies Immune Globulin (Human) dose of 20 IU/kg of rabies antibody was given simultaneously with the first dose of vaccine, levels of passive rabies antibody were detected 24 hours after injection in all individuals. There was minimal or no interference with the immune response to the initial and subsequent doses of vaccine, including booster doses.
Studies of Rabies Immune Globulin (Human), 27 Imogam® Rabies, given with the first of five doses of Aventis Pasteur SA HDCV1 confirmed that passive immunization with 20 IU/kg of Rabies Immune Globulin (Human) provides maximum circulating antibody with minimum interference of active immunization by HDCV.
A double-blind randomized trial28 was conducted to compare the safety and antibody levels achieved following intramuscular injection of Imogam® Rabies – HT (heat treated) and Rabies Immune Globulin (Human), Imogam® Rabies (non-heat treated). Each Rabies Immune Globulin (Human) was administered on day 0, either alone or in combination with the human diploid cell Rabies Vaccine (Imovax® Rabies) using the standard postexposure prophylactic schedule of day 0, 3, 7, 14, and 28.
Sixty-four healthy veterinary student volunteers were randomized into four parallel groups of 16 each to receive the following Rabies Immune Globulin (Human) and vaccine regimens:
Imogam® Rabies HT + Imovax®
Imogam® Rabies + Imovax®
Imogam® Rabies HT + placebo
Imogam® Rabies + placebo
The treatment of both Rabies Immune Globulin (Human) and vaccine corresponded to the postexposure recommended dose of 20 IU/kg of Rabies Immune Globulin (Human) and was administered in three, equally divided IM injections of under 5 mL in either gluteus. Serum rabies antibody levels were assessed before treatment and on days 3, 7, 14, 28, 35, and 42 by the Rabies Fluorescent Focus Inhibition Test (RFFIT).
Serum antibody levels were similar in the Imogam® Rabies – HT (rabies immune globulin (human)) and Imogam® Rabies groups. By day three, 60% of each group had detectable antibody titers of ≥ 0. 05 IU/mL. By day 14, the geometric mean titers (with 95% confidence interval) were 19 IU/mL (11-38) in the Imogam® Rabies – HT (rabies immune globulin (human)) + vaccine group and 31 IU/mL (20 to 48) in the Imogam® Rabies + vaccine group. These differences were not statistically different.
Two subjects reported severe headaches, one in the Imogam® Rabies – HT (rabies immune globulin (human)) + placebo group and one in the Imogam® Rabies + Imovax® Rabies group. One third of the volunteers had moderate systemic (headache and malaise) reactions. These were equally distributed among the 4 treatment groups with no significant differences between the groups.
Both Imogam® Rabies – HT (rabies immune globulin (human)) and Imogam® Rabies were safe and without serious adverse events or allergic reactions. The safety profile did not differ between groups, although Imogam® Rabies – HT (rabies immune globulin (human)) produced fewer and milder local reactions such as pain or tenderness at the injection site.
1. Recommendation of the Advisory Committee on Immunization Practices (ACIP). Human Rabies prevention – United States, 1999. MMWR 48:No. RR-1, 1999
2. Krebs JW, et al. Rabies surveillance in the United States during 1996. J Am Vet Med Assoc 211:1525-1539, 1997
3. Noah DL, et al. Epidemiology of human rabies in the United States, 1980 to 1996. Ann Intern Med 128:922-930, 1998
4. Centers for Disease Control and Prevention (CDC). Human Rabies – New Hampshire, 1996. MMWR 46:267-270, 1997
5. Mitmoonpitak C, et al. Current status of animal rabies in Thailand. J Vet Med Sci 59:457-460, 1997
6. CDC. Human rabies – Montana and Washington, 1997. MMWR 46:770-774, 1997
7. CDC. Human rabies – Texas and New Jersey, 1997. MMWR 47:1-5, 1998
8. Krebs JW, et al. Causes, costs and estimates of rabies postexposure prophylaxis treatments in the United States. J Public Health Manage Pract 4:57-63, 1998
9. Bernard KW, et al. Neuroparalytic illness and human diploid cell rabies vaccine. JAMA 248:3136-3138, 1982
10. CDC. Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR 33: 185-187, 1984
11. Dreesen EW, et al. Immune complex-like disease in 23 persons following a booster dose of rabies human diploid cell vaccine. Vaccine 4:45-49, 1986
12. Aoki FY, et al. Immunogenicity and acceptability of a human diploid-cell culture rabies vaccine in volunteers. Lancet 1: 660-662, 1975
13. Cox JH, et al. Prophylactic immunization of humans against rabies by intradermal inoculation of human diploid cell culture vaccine. J Clin Microbiol 3:96-101, 1976
14. Anderson LJ, et al. Postexposure trial of a human diploid cell strain rabies vaccine. J Infect Dis 142:133-138, 1980
15. Bahmanyar M, et al. Successful protection of humans exposed to rabies infection. Postexposure treatment with the new human diploid cell rabies vaccine and antirabies serum. JAMA 236:2751-2754, 1976
16. Hattwick MAW. Human rabies. Public Health Rev 3:229-274, 1974
17. Wiktor TJ, et al. Development and clinical trials of the new human rabies vaccine of tissue culture (human diploid cell) origin. Dev Biol Stand 40:3-9, 1978
18. World Health Organization (WHO). WHO expert committee on rabies. Seventh Report. Geneva. WHO Tech Rep Ser 709:1-104, 1984
19. Kuwert EK, et al. Immunization against rabies with rabies immune globulin, human (RIGH) and a human diploid cell strain (HDCS) rabies vaccine. J Biol Stand 6:211-219, 1978
20. Wilde H, et al. Failure of postexposure treatment of rabies in children. Clin Infect Dis 22:228-232, 1996
21. CDC. Human rabies despite treatment with rabies immune globulin and human diploid cell rabies vaccine – Thailand. MMWR 36: 759-760, 765, 1987
22. Shill M, et al. Fatal rabies encephalitis despite appropriate postexposure prophylaxis. A case report. N Engl J Med 316: 1257-1258, 1987
23. Wilde H, et al. Failure of rabies postexposure treatment in Thailand. Vaccine 7:49-52, 1989
24. Habel K, et al. Laboratory data supporting clinical trial of antirabies serum in persons bitten by rabid wolf. Bull WHO 13: 773-779, 1955
25. Cabasso VJ, et al. Rabies immune globulin of human origin: preparation and dosage determination in non-exposed volunteer subjects. Bull WHO 45:303-315, 1971
26. Loofbourow JC, et al. Rabies immune globulin (human). Clinical trials and dose determination. JAMA 217:1825-1831, 1971
27. Helmick CG, et al. A clinical study of Mérieux human rabies immune globulin. J Biol Stand 10:357-367, 1982
28. Lang J, et al. Evaluation of the safety and immunogenicity of a new, heat-treated human rabies immune globulin using a sham, postexposure prophylaxis of rabies. Biologicals 26:7-15, 1998
Last reviewed on RxList: 10/23/2008
This monograph has been modified to include the generic and brand name in many instances.
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