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 Post-Exposure 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 three 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 three 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.

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