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Rabies exposure assessment & rabies vaccine |
1. Who should consider rabies pre-exposure rabies immunization? |
Pre-exposure immunization may be offered to persons in high-risk groups, such as veterinarians, animal handlers, certain laboratory workers, and persons spending time (e.g. 1 month or more) in foreign countries where rabies is a constant threat. Persons whose vocational or avocation pursuits bring them into contact with potentially rabid dogs, cats, foxes, skunks, bats, or other species at risk of having rabies should also be considered for pre-exposure prophylaxis.
Pre-exposure prophylaxis is given for several reasons. First, it may provide protection to persons with inapparent exposures to rabies. Second, it may protect persons who might have a delay in obtaining post-exposure therapy after an exposure. Finally, although it does not eliminate the need for additional therapy after a rabies exposure, it simplifies therapy by eliminating the need for rabies immune globulin and decreasing the number of doses of vaccine needed. This is of particular importance for persons at high risk of being exposed in countries where the available rabies immunizing products may carry a higher risk of adverse reactions.
Pre-exposure immunization does not eliminate the need for prompt post-exposure prophylaxis; it only reduces the post-exposure regimen.
| Criteria for Pre-exposure Immunization*** |
| Risk category |
Nature of risk |
Typical populations |
Pre-exposure regimen |
| Continuous |
Virus present continuously, often in high concentrations. Aerosol, mucous membrane, bite or non bite exposure possible. Specific exposures may go unrecognized. |
Rabies research lab workers.* Rabies biologics production workers. |
Primary pre-exposure immunization course. Serology every 6 months. Booster immunization when antibody titer falls below acceptable level.* |
| Frequent |
Exposure usually episodic, with source recognized, but exposure may also be unrecognized. Aerosol, mucous membrane, bite or non bite exposure |
Rabies diagnostic lab workers,* spelunkers, veterinarians, and animal control and wildlife workers in rabies epizootic areas. |
Primary pre-exposure immunization course. Booster immunization or serology every 2 years.** |
Infrequent
(greater than population-at-large) |
Exposure nearly always episodic with source recognized. Mucous membrane, bite, or non bite exposure. |
Veterinarians and animal control and wildlife workers in areas of low rabies endemicity. Certain travelers to foreign rabies epizootic areas. Veterinary students. |
Primary pre-exposure immunization course. No routine booster immunization or serology. |
Rare
(population-at-large)
|
Exposure always episodic, mucous membrane, or bite with source recognized. |
U.S. population-at-large, including individuals in rabies-epizootic areas. |
No pre-exposure immunization. |
*Judgment of relative risk and extra monitoring of immunization status of lab workers are the responsibility of the laboratory supervisor (see U.S. Department of Health and Human Services Biosafety in Microbiological and Biomedical Laboratories, 1984).
**Pre-exposure booster immunization consists of one dose of HDCV, 1.0 ml/dose, IM (deltoid area). Acceptable antibody level is 1:5 titer (complete inhibition in RFFIT at 1:5 dilution). Boost if titer falls below 1:5.
***Source: Centers for Disease Control: Human Rabies Prevention - United States, 1999: Recommendations of the Advisory Committee (ACIP) MMWR 48 (No. RR-1): 1-21. |
2. What vaccines are used for pre-exposure immunization? |
There are 3 rabies vaccines licensed for use in the United States as appropriate for pre-exposure situations. Human Diploid Cell Vaccine (HDCV) is available in an intramuscular (IM) formulation. HDCV is an inactivated virus vaccine prepared from fixed rabies grown in MRC-5 human diploid cell culture. The vaccine is produced in France (Merieux Institute's IMOVAX® RABIES) and is distributed by Aventis-Pasteur (800-VACCINE). The virus is inactivated with B-propiolactone. The vaccine is available in a 1.0 ml single-dose vial of lyophilized vaccine with accompanying diluent. Since neither the vaccine nor diluent contain preservatives, the reconstituted vaccine must be used immediately.
Rabies Vaccine Absorbed (RVA) is available as a 1.0 ml IM formulation. It is produced by the Bioport Company and is distributed by Glaxo-Smith Kline via its wholesaler network. In King county, the wholesaler is: Physician Sales and Supply (253-872-9896). The vaccine is prepared from the Kissling strain of Challenge Virus Standard (CVS) rabies virus adapted to fetal rhesus lung diploid cell culture. The vaccine virus is inactivated with betapropriolactone and concentrated by adsorption to aluminum phosphate. Because RVA is adsorbed to aluminum phosphate, it is liquid rather than lyophilized.
RabAvert® is a Purified Chick Embryo Cell Vaccine (PCEC) and is available in a single dose vial that is reconstituted in the vial with the accompanying diluent to make a final volume of 1.0 ml. It is produced by Chiron Corporation. It can be ordered directly from the company at (888) 244-7667.
All of these vaccines are safe and effective when used as indicated. The full 1.0 ml dose of any of these products can be used for both pre-exposure and post-exposure treatment.
Since most of the vaccine administered in the United States is HDCV (Imovax®), from here forward, we will reference this vaccine exclusively.
3. What is the recommended method for administering pre-exposure rabies immunization? |
Three 1.0 ml injections of HDCV should be given intramuscularly in the deltoid muscle, one on each of days 0, 7, and 21 or 28. In a study in the United States, more than 1,000 persons received HDCV according to this regimen; antibody was demonstrated in the sera of all subjects when tested by the rapid fluorescent-focus inhibition test (RFFIT). Other studies have produced comparable results. Because the antibody response following the recommended vaccination regimen with HDCV has been so satisfactory, routine post-vaccination serology is not recommended.
4. What guidelines are used locally to determine if someone needs post exposure treatment? |
The following recommendations are only a guide. In applying them, take into account the animal species involved, the circumstances of the bite or other exposure to the animal's saliva, the vaccination status of the animal, and presence of rabies in the geographic region where the bite occurred. In Washington, rabies is endemic among bats.
Rabies postexposure prophylaxis guide
| Animal species |
Condition of animal at time of attack |
Treatment of exposed person |
| Dog Cat, Ferret |
Healthy and available for ten days of observation. If animal becomes sick or dies within the 10 days of observation, have the animal tested for rabies. |
Should not begin prophylaxis unless animal develops clinical signs of rabies1,2 |
| Dog Cat, Ferret |
Known to be rabid or suspected to be rabid (provoked or unprovoked bite) or if the status of the animal is unknown, and the bite was unprovoked. Bites that occurred in a developing country should be considered suspected rabid as animals are not often immunized against rabies. |
Treatment indicated. Give RIG and HDCV as indicated. Report incident to Public Health, (206) 296-4774. |
| Bat |
Regard as rabid unless proven by laboratory tests that the bat was not rabid. |
Treatment is indicated if there is a known, or reasonable probability, that direct contact with the bat occurred, give RIG and HDCV. Report incident to Public Health, (206) 296-4774. |
| Skunk, Coyote, Raccoon, Bobcat, Bear, Fox, and Other Carnivores |
Regarded as rabid unless animal proven negative by laboratory tests. |
Consider immediate vaccination |
| Livestock, Rodents, And Lagomorphs (Rabbits And Hares) |
Consider individually. Call Public Health as necessary for guidance. Bites from squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other rodents, rabbits, and hares almost never call for antirabies prophylaxis. |
1All bites and wounds should be thoroughly cleansed immediately with soap and water. If antirabies treatment is indicated, both rabies immune globulin (RIG) and human diploid cell rabies vaccine (HDCV) should be given as soon as possible.
2During the usual holding period of 10 days, begin treatment with RIG and HDCV at first sign of rabies in a dog, cat, or ferret. The symptomatic animal should be killed immediately and tested. Holding for observation is not recommended. Discontinue vaccine if immunofluorescence test results of the animal are negative. |
5. What post-exposure rabies prophylaxis is recommended for a person who previously completed a pre-exposure immunization regimen and who is exposed to a confirmed or suspected rabid animal? |
When a person is exposed to rabies and has previously received a three dose vaccination series of HDCV, or has previously demonstrated rabies antibody, two IM doses (1.0 ml each) of HDCV in the deltoid muscle should be administered. Give one dose immediately and one 3 days later. Rabies immune globulin (RIG) is not indicated.
If the immune status of a partially vaccinated person is not known, a full post-exposure antirabies treatment (RIG plus five doses of HDCV) will be necessary. In such cases, if antibody can be demonstrated in a serum sample collected before the final three doses of vaccine are given, treatment can be discontinued once at least two post-exposure doses of HDCV have been administered. Since serologic tests are only performed out of state, it may be difficult to obtain the necessary results in time to avoid giving the last 3 rabies vaccine doses.
6. What is the recommended post-exposure prophylaxis for persons with no previous rabies immunization or with an inadequate rabies antibody titer? |
Post-exposure antirabies immunization should always include administration of both RIG and HDCV with one exception. Persons who have been previously immunized with the recommended pre- or post-exposure regimens using HDCV, or other vaccines, and who have documented adequate rabies antibody titer may receive only vaccine. Consult question number
For all other situations, the combination of RIG and rabies vaccine is recommended for both bite and non-bite exposures, regardless of the interval between the exposure and the initiation of post-exposure prophylaxis (PEP). Begin PEP as soon as possible after exposure for maximum protection.
Five 1 ml (IM) doses of HDCV should be given intramuscularly in the deltoid muscle. The first dose of IM Rabies Vaccine should be given as soon as possible after the exposure; an additional dose should be given on days 3, 7, 14, and 21 or 28 after the first dose. Because the antibody response following the recommended vaccination regimen with HDCV has been so satisfactory, routine post-vaccination serologic testing is not recommended. In unusual instances, as when the patient is known to be immunosuppressed, serologic testing is indicated.
RIG is dosed according to weight and is administered only once, at the beginning of antirabies prophylaxis, to provide immediate, protective antibodies until the patient responds to HDCV by active production of antibodies. Rabies Immune Globulin, Human (RIG) produced by the Bayer Company (BAYRAB®) and Adventis Pasteur (IMOGAM® RABIES-HT). These are anti-rabies gamma globulins concentrated by cold ethanol fractionation from plasma of hyperimmunized human donors. Rabies neutralizing antibody content is standardized to contain 150 international units (IU) per ml. It is supplied in 2 ml (300 IU) and 10 ml. (1,500 IU) vials for pediatric and adult use, respectively.
If RIG was not given when rabies vaccination was begun, it should be administered as early as possible, but no later than the seventh day after the first dose of vaccine was given. From the eighth day on, RIG is not indicated, since an antibody response to the vaccine is presumed to have occurred. The recommended dose of RIG is 20 IU/kg or approximately 9 IU/lb of body weight. If anatomically feasible, the full dose of RIG should be thoroughly infiltrated in the area around the wound, the remainder should be administered intramuscularly. RIG should be administered into a different intramuscular site from HDCV. Because RIG may partially suppress active production of antibody, no more than the recommended dose of RIG should be given.
7. How often should booster doses of rabies vaccine be administered? |
Persons who work with live rabies virus in research laboratories or vaccine production facilities and are at risk of inapparent exposure should have the rabies antibody titer of their serum determined every 6 months; booster doses of vaccine should be given, as needed, to maintain an adequate titer.
Laboratory workers who handle rabies diagnostic tests, and spelunkers, veterinarians, animal control and wildlife officers who work in areas where animal rabies is epizootic, should have boosters doses of rabies vaccine (IM or ID) every 2 years, or have their serum tested for rabies antibody every 2 years and, if the titer is inadequate, have a booster dose. International travelers, veterinarians and animal control and wildlife officers, working or traveling in areas of low rabies endemicity, do not require routine booster doses of HDCV after completion of the primary pre-exposure immunization.
8. What adverse reactions may occur in persons receiving Human Diploid Cell Vaccine (HDCV) and Human Rabies Immune Globulin (RIG)? |
HDCV
In studies using five doses of HDCV, local reactions, such as pain, erythema, and swelling or itching at the injection site, were reported in about 30 to 74% of vaccine recipients. Systemic reactions, such as headache, nausea, abdominal pain, muscle aches, and dizziness were reported in about 5 to 40% of vaccine recipients. Three cases of neurologic illness resembling Guillain-Barre' syndrome that resolved without sequelae within 12 weeks have been reported. In addition, other central and peripheral nervous system disorders have been temporally associated with HDCV vaccine, but a causal relationship has not been established in these rare reports.
An "immune complex-like" serum sickness reaction has occurred among approximately 6% of persons who received booster doses of HDCV. The illness, characterized by onset 2-21 days post booster dose, presents with a generalized urticaria and may also include arthralgia, arthritis, angioedema, nausea, vomiting, fever, and malaise. This reaction has occurred less frequently among persons receiving primary vaccination. The reactions have been associated with the presence of betapropiolactone-altered human albumin in the HDCV and the development of immunoglobulin E (IgE) antibodies to this allergen.
Once initiated, post-exposure rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Usually such reactions can be successfully managed with anti-inflammatory and antipyretic agents. When a person with a history of serious hypersensitivity to rabies vaccine must be revaccinated, antihistamines can be administered. Epinephrine should be readily available to manage anaphylactic reactions.
Serious systemic anaphylactic or neuroparalytic reactions occurring during the administration of rabies vaccines pose a serious dilemma for the attending physician. A patient's risk of developing rabies must be carefully considered before deciding to discontinue vaccination.
All serious reactions to rabies vaccine should be reported to the Vaccine Adverse Event Reporting System (VAERS). This can be done locally by telephoning Public Health (206) 296-4774 to make a report or by calling the national hotline at (800) 822-7967.
RIG
Local pain and low-grade fever may follow receipt of RIG. Although not reported specifically for RIG, angioneurotic edema, nephrotic syndrome, and anaphylaxis have been reported after injection of immune serum globulin (ISG), a product similar in biochemical composition, but without antirabies activity. These reactions occur so rarely that the causal relationship between ISG and these reactions is not clear.
Both formulations of RIG undergo multiple viral clearance procedures during preparation. There is no evidence that any viruses have ever been transmitted by commercially available RIG in the United States.
9. What additional precautions should be taken when administering HDCV? |
Persons with history of hypersensitivity to vaccines or vaccine components should be given rabies vaccines with caution. When a patient with a history suggesting hypersensitivity to HDCV must be given that vaccine, antihistamines can be given; epinephrine should be readily available to counteract anaphylactic reactions, and the person should be carefully observed.
Corticosteroids, other immunosuppressive agents, and immunosuppressive illnesses can interfere with the development of active immunity and predispose the patient to vaccine failure. Immunosuppressive agents should not be administered during post-exposure therapy, unless they are essential for the treatment of other conditions. When rabies post-exposure prophylaxis is administered to persons receiving steroids or other immunosuppressive therapy, it is important that, at the completion of the vaccination series, serologic testing for rabies antibody is done.
10. What considerations exist for international travelers receiving rabies vaccines? |
When an international traveler is recommended to have rabies pre-exposure prophylaxis, the IM dose/route of administration provides sufficient antibody response to overcome the immune system interference that antimalarial drugs such as chloroquine phosphate and mefloquine may cause.
11. Can pre-exposure and post-exposure rabies prophylaxis be safely administered during pregnancy? |
Because of the potential consequences of an inadequately treated rabies exposure, and limited data which fail to implicate that fetal abnormalities are associated with rabies vaccination, pregnancy is not considered a contraindication to post-exposure prophylaxis. If there is substantial risk of exposure to rabies, pre-exposure prophylaxis may also be indicated during pregnancy.
12. How may rabies vaccine (HDCV) be ordered? |
HDCV may be ordered (by physicians) from Aventis-Pasteur, Discovery Drive, Swiftwater, Pennsylvania 18370, or by phoning 1-800-822-2463. There are no shipping charges for regular, 2 day-delivery. Overnight delivery is available for a fee of approximately $20.00. No minimum order is required. IM doses are priced at about $120 per dose.
13. How may RIG be obtained? |
RIG may be ordered from the manufacturer. RIG is supplied as 2.0 or 10.0 mls vials that are standardized to contain 150 international unit (IU) of rabies neutralizing antibody per ml. The volume of RIG to be administered is dependent on the weight of the recipient. The dosage is 20 IU/kg (0.133 ml/kg) or 9 IU/lb (0.06 ml/lb). Therefore, a person who weighs 100 lbs. requires 6 ml. of RIG. When administering RIG, it is important not to exceed the recommended dosage.
BAYRAB® may be obtained from Customer Operations, Bayer Corporation, Biologics Products, 400 Morgan Lane, West Haven, CT 06516, telephone, 1-800-288-8370. It may also be shipped by a pharmaceutical wholesaler.
IMOGAM® RABIES-HT may be obtained from Aventis-Pasteur, Discovery Drive, Swiftwater, Pennsylvania 18370 or by telephone, 1-800-822-2463. IMOGAM® RABIES-HT is heat treated and contains no preservatives. RIG that remains from partially used vials should be discarded immediately. Please consider this when making an order for this product. The cost for RIG is approximately $50 to $60 per ml.
14. Are there any other ways to obtain RIG and rabies vaccine urgently? |
A few local hospital pharmacies carry a supply. Public Health - Seattle & King County clinic sites do not carry RIG, but some clinic sites carry a supply of HDCV. Call (206) 296-4774 for information.
15. Can patients get rabies vaccinations at Public Health - Seattle & King County? |
Public Health administers pre-exposure doses of HDCV at cost through its travel clinic locations only. No preauthorization for pre-exposure rabies vaccine doses is necessary.
Public Health clinics can administer IM rabies vaccine for post-exposure purposes at any of its clinic locations with prior authorization from, and arrangement by, Public Health's Communicable Disease Epidemiology and Immunization section, (206-296-4774). Please call if you plan to refer a patient to Public Health. Public Health does not usually stock supplies of RIG which is available through community health care providers.
Persons who are insured (especially those who are covered by a preferred provider or health maintenance organization) should be referred according to specific plan guidelines to obtain vaccination. Public Health resources should be reserved for patients who do not have insurance coverage or who lack access to a health care provider. Public Health charges patients for treatment.
16. What is the standard test for determining rabies antibodies? Where may sera be sent for rabies antibody testing? |
This serologic test is not available locally. Serologic samples must be collected and then prepared for shipment to one of the laboratories below. At least 2.0 ml of serum should be sent for testing. Specimens should be shipped on ice packs in a leakproof package. Express shipping (i.e. UPS, FedEx, Airborne) should be used to send the specimen. Please call the laboratories for more specific instructions on how to submit specimens for testing.
Kansas State University
Veterinary Diagnostic Laboratory
Kansas State University
School of Veterinary Medicine
1800 Bennison Ave
Manhattan, Kansas 66506
(785) 532-5650
Atlanta Health Associates
309 Pirkle Ferry Road, Suite D-300
Cumming, GA 30040
(770) 205-9091 or 1-800-717-5612
Fax: 770-205-9021
17. What is considered the minimally acceptable rabies antibody titer following immunization? |
The Centers for Disease Control and Prevention (CDC, U.S. Public Health Service) considers a complete viral neutralization at a 1:5 or greater titer by the rapid fluorescent-focus inhibition test (RFFIT) as acceptable at 1:5 dilution or greater; the World Health Organization specifies 0.5 IU/mL or more acceptable.
18. Is any treatment indicated if an individual is accidentally exposed to modified live rabies virus (MLV) vaccines (vaccines given to animals)? |
Individuals may be accidentally exposed to attenuated rabies virus while administering MLV vaccines to animals. While there have been no reported human rabies cases resulting from exposure to needlesticks or sprays with licensed MLV vaccines, vaccine-induced rabies has been observed in animals given MLV vaccines. Absolute assurance of a lack of risk for humans, therefore, cannot be given. The best evidence for a low risk, however, is the absence of recognized cases of vaccine-associated disease in humans despite frequent accidental exposures.
Currently available MLV animal vaccines are made with one of two attenuated strains of rabies virus: high egg passage (HEP) Flury strain or Street Alabama Dufferin (SAD) strain. The HEP Flury and SAD virus strains have been used in animal vaccines for over 10 years without evidence of associated disease in humans; therefore, post-exposure treatment is not recommended following exposure to these types of vaccine by needlestick or sprays.
Because data is insufficient to assess the true risk associated with any of the MLV vaccines, pre-exposure immunization, and periodic boosters are recommended for all persons who deal with potentially rabid animals or who frequently handle animal rabies vaccines.
References used to prepare this document |
- Human Rabies Prevention - United States, 1999 Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 48(RR-1); 1-21., January 8, 1999.
- Public Health - Seattle & King County Immunization Manual
- Control of Communicable Diseases Manual. American Public Health Association, 17th edition, 2000.
- 2000 Red Book: Report of the Committee on Infectious Diseases. American Academy of Pediatrics, 2000.
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