Rabies Immune Globulin (Human) IMOGAM ^® RABIES - HT is indicated for individuals suspected of exposure to rabies, particularly severe exposure, with one exception: persons who have been previously immunized with HDCV Rabies Vaccine in a pre or postexposure treatment series should receive only vaccine. Persons who have received Rabies Vaccines other than HDCV or RVA vaccines should have confirmed adequate rabies antibody titers if they are to receive only vaccine. ¹

IMOGAM ^® RABIES - HT should be injected as promptly as possible after exposure along with the first dose of vaccine. If initiation of treatment is delayed for any reason, IMOGAM ^® RABIES - HT and the first dose of vaccine should still be given, regardless of the interval between exposure and treatment. IMOGAM ^® RABIES - HT may be given up to eight days after the first dose of vaccine was given.

Rabies virus is usually transmitted by the bite of a rabid animal but can occasionally penetrate abraded skin contaminated with the saliva of infected animals. Progress of the virus after exposure is believed to follow a neural pathway and the time between exposure and clinical rabies is a function of the proximity of the bite (or abrasion) to the central nervous system and the dose of virus injected. The incubation is usually 2 to 6 weeks but can be longer. After severe bites about the face and neck and arms, it may be as short as 10 days. After initiation of the vaccine series (human diploid cell origin), it takes approximately one week for development of immunity to rabies; therefore, the value of immediate passive immunization with rabies antibodies in the form of Rabies Immune Globulin (Human) cannot be overemphasized.

Recommendations for passive and/or active immunization after exposure to an animal suspected of having rabies have been outlined by the WHO ³¹ and by the United States Public Health Service Advisory Committee on Immunization Practices (ACIP). ¹

I. Rationale of Treatment

In the United States and Canada the following factors should be considered before specific antirabies treatment is indicated:

1. Species of Biting Animal

Carnivorous animals (especially skunks, foxes, coyotes, raccoons, dogs, bobcats, and cats) and bats are more likely to be infected with rabies than other animals. Rats, mice, squirrels, hamsters, guinea pigs, gerbils, chipmunks and other rodents or rabbits and hares are rarely infected with rabies and have not been known to cause human rabies in the United States. Their bites almost never call for antirabies prophylaxis; therefore, before initiating antirabies prophylaxis, the local or state health department should be consulted.

Because some bat bites may be less severe, and therefore more difficult to recognize, than bites inflicted by larger mammalian carnivores, rabies postexposure treatment should be considered for any physical contact with bats when bite or mucous membrane contact cannot be excluded. ^32,33

2. Circumstances of Biting Incident

An UNPROVOKED attack is more likely than a provoked attack to indicate that the animal is rabid. Bites inflicted on a person attempting to feed or handle an apparently healthy animal should generally be regarded as PROVOKED.

3.Type of Exposure

Rabies is commonly transmitted by inoculation with infectious saliva. The likelihood that rabies infection will result from exposure to a rabid animal varies with the nature and extent of the exposure. Two categories of exposure should be considered:

Bite: Any penetration of the skin by teeth.

Nonbite: Scratches, abrasions, open wounds or mucous membranes contaminated with saliva or other potentially infectious material such as brain tissue from a rabid animal.

In addition, two cases of rabies have been attributed to airborne exposures in laboratories and two cases of rabies have been attributed to probable exposures to a bat- infested cave (Frio Cave, Texas). ^{1,34 - 36} Casual contact with a rabid animal, such as petting the animal (without a bite or nonbite exposure as described above) does not constitute an exposure and is not an indication for prophylaxis.

The only documented cases of rabies due to human-to-human transmission occurred in patients who received corneas transplanted from persons who died of rabies undiagnosed at the time of death. ^1,37

Each exposure to possible rabies infection must be individually evaluated. Local or state public health officials should be consulted if questions arise about the need for rabies prophylaxis.

4.Vaccination Status of Biting Animal

A properly immunized animal has only a minimal chance of developing rabies and transmitting the virus.

II. Postexposure Treatment of Rabies

1. Local Treatment of Wounds

Immediate and thorough local treatment of all bite wounds and scratches is perhaps the most effective preventive measure. The wound should be thoroughly cleansed immediately with soap and water. Tetanus prophylaxis and measures to control bacterial infection should be given as indicated.

2. Specific Treatment

Postexposure antirabies treatment should always include both passive (preferably Rabies Immune Globulin - Human) and active (preferably Rabies Vaccine prepared from human diploid cells) immunization with one exception: persons who have been previously immunized with HDCV Rabies Vaccine in a pre or postexposure treatment series should receive only vaccine. Persons who have received Rabies Vaccines other than HDCV or RVA vaccines should have confirmed adequate rabies antibody titers if they are to receive only vaccine. ¹ The combination of globulin and vaccine is recommended for both bite exposures and nonbite exposures (as described under "Rationale of Treatment") and regardless of the interval between exposure and treatment. The sooner treatment is begun after exposure, the better.

3. Postexposure Treatment Guide

The following recommendations are only a guide. They should be applied in conjunction with knowledge of the animal species involved, circumstances of the bite or other exposure, vaccination status of the animal, and presence of rabies in the region. Local and state public health officials should be consulted if questions arise about the need for rabies prophylaxis.

* During the 10-day holding period, begin treatment with HRIG and HDCV or RVA at first sign of rabies in a dog or cat that has bitten someone. The symptomatic animal should be killed immediately and tested.

^†The animal should be killed and tested as soon as possible. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative.

Parenteral drug products should be inspected visually for particulate matter and/or discoloration prior to administration, whenever solution and container permit. If either of these conditions exist, the vaccine should not be administered.

IMOGAM ^® RABIES - HT should be used in conjunction with Rabies Vaccine such as R.B.E. VACCINE IMOVAX ^® RABIES, for intramuscular immunization, vaccine prepared from human diploid cell cultures. The recommended dose of IMOGAM ^® RABIES - HT is 20 IU/kg (0.133 mL/kg) or 9 IU/lb (0.06 mL/lb) of body weight administered at time of the first vaccine dose. ^27,28 As much as possible of the recommended dose should be infiltrated around the wound if anatomically feasible and the remaining HRIG should be administered intramuscularly in the gluteal region. ⁴⁵ Two injections would be given in the gluteal region if the volume is greater than 5 mL.

HRIG should never be administered in the same syringe or into the same anatomical site as vaccine. Because HRIG may partially suppress active production of antibody, no more than the recommended dose should be given. ¹

IMOGAM ^® RABIES - HT is supplied in 2 mL and 10 mL vials with average potency of 150 International Units per milliliter (IU/mL). The 2 mL vial contains 300 IU which is sufficient for a child weighing 15 kg (33 lb). Product No. 49281-190-20.The 10 mL vial contains a total of 1,500 IU which is sufficient for an adult weighing 75 kg (165 lb). Product No. 49281-190-10

STORAGE

IMOGAM ^® RABIES - HT should be stored in the refrigerator between 2° and 8° C (35° and 46° F). Do not freeze.

IMOGAM ^® RABIES - HT CONTAINS NO PRESERVATIVE AND UNUSED PORTION MUST BE DISCARDED IMMEDIATELY.

REFERENCES

1. Recommendation of the Advisory Committee on Immunization Practices (ACIP). Rabies prevention - United States, 1991. MMWR 40: No. RR-3, 1991

2. Reid- Sanden FL, et al. Rabies surveillance, United States during 1989. J Am Vet Med Assoc 197: 1571-1583, 1990

3. Helmick CG. The epidemiology of human rabies postexposure prophylaxis, 1980-1981. JAMA 250: 1990-1996, 1983

4. C.C. Human rabies diagnosed 2 months postmortem - Texas. MMWR 34: 700, 705-707, 1985

5. C.C. Human rabies acquired outside the United States. MMWR 34: 235-236, 1985

6. C.C. Human rabies - California, 1987. MMWR 37: 305-308, 1988

7. C.C. Human rabies - Oregon, 1989. MMWR 38: 335-337, 1989

8. C.C. Human rabies - Texas. MMWR 33: 469-470, 1984

9. C.C. Imported human rabies. MMWR 32: 78-80, 85-86, 1983

10. C.C. Human rabies acquired outside the United States from a dog bite. MMWR 30: 537-540, 1981

11. Bernard, KW, et al. Neuroparalytic illness and human diploid cell rabies vaccine. JAMA 248: 3136-3138, 1982

12. C.C. Systemic allergic reactions following immunization with human diploid cell rabies vaccine. MMWR 33: 185-187, 1984

13. 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

14. Aoki FY, et al. Immunogenicity and acceptability of a human diploid- cell culture rabies vaccine in volunteers. Lancet 1: 660-662, 1975

15. 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

16. Anderson LJ, et al. Postexposure trial of a human diploid cell strain rabies vaccine. J Infect Dis 142: 133-138, 1980

17. 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

18. Hattwick MAW. Human rabies. Public Health Rev 3: 229-274, 1974

19. 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

20. World Health Organization. WHO expert committee on rabies. WHO Tech Rep Ser 709: 1-104, 1984

21. 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

22. C.C. Human rabies despite treatment with rabies immune globulin and human diploid cell rabies vaccine - Thailand. MMWR 36: 759-760, 765, 1987

23. Shill M, et al. Fatal rabies encephalitis despite appropriate post-exposure prophylaxis. A case report. N Engl J Med 316: 1257-1258, 1987

24. Wilde H, et al. Failure of rabies postexposure treatment in Thailand. Vaccine 7: 49-52, 1989

25. Baltazard M, et al. Essai pratique du serum antirabique chez les mordus par loups enrages. Bull WHO 13: 747-772, 1955

26. Habel K, et al. Laboratory data supporting clinical trial of antirabies serum in persons bitten by rabid wolf. Bull WHO 13: 773-779, 1955

27. 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

28. Loofbourow JC, et al. Rabies immune globulin (human). Clinical trials and dose determination. JAMA 217: 1825-1831, 1971

29. Helmick CG, et al. A clinical study of Mérieux human rabies immune globulin. J Biol Stand 10: 357-367 1982

30. Lang J, et al. A clinical evaluation of a new heat treated Rabies Immune Globulin (Human). VII Annual International Meeting on Research Advances & Rabies Control in the Americas. Centers for Disease Control & Prevention, Atlanta, Georgia, December 9-13, 1996

31. WHO Expert Committee on Rabies. WHO Tech Rep Ser 523: 50-51, 1973

32. ACIP. Human Rabies - California, 1994. MMWR 43: 455-457, 1994

33. Wilde H, et al. Failure of Postexposure Treatment of Rabies in Children. Clin Infect Dis 22: 228-232, 1996

34. Afshar A. A review of non- bite transmission of rabies virus infection. Br Vet J 135: 142-148, 1979

35. Winkler WG, et al. Airborne rabies transmission in a laboratory worker. JAMA 226: 1219-1221, 1973

36. C.C. Rabies in a laboratory worker - New York. MMWR 26: 183-184, 1977

37. Gode GR, et al. Two rabies deaths after corneal grafts from one donor {letter}. Lancet 2: 791, 1988

38. Fudenberg HH. Sensitization to immunoglobulins and hazards of gamma globulin therapy, pp 211-220 in Merler E, Editor Immunoglobulins: biologic aspects and clinical uses. National Academy of Sciences, Wash., DC. 1970

39. Pineda AA, et al. Transfusion reactions associated with anti- lgA antibodies: report of four cases and review of the literature. Transfusion 15: 10-15, 1975

40. Janeway CA, et al. The gamma globulins. IV. Therapeutic uses of gamma globulins. N Engl J Med 275: 826-831, 1966

41. Kjellman H. Adverse reactions to human immune serum globulin in Sweden (1969-1978). pp 143-150. Immunoglobulins: characteristics and uses of intravenous preparations. Alving BM and Finlayson JS, Editors. US Dept. Health & Human Services, DHHS Publ. No. (FDA) 80-9005,Wash., DC. 1980

42. C.C. Vaccine Adverse Event Reporting System - United States. MMWR 39: 730-733, 1990

43. C.C. National Childhood Vaccine Injury Act. Requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 37: 197-200, 1988

44. Food and Drug Administration. New Reporting Requirements for Vaccine Adverse Events. FDA Drug Bull 18( 2), 16-18, 1988

45. World Health Organization. WHO expert committee on rabies. WHO Tech Rep Ser 824:1992

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