What are the indications for rabies immunoglobulin (RIG) administration in individuals exposed to rabies, particularly those who are unvaccinated or immunocompromised?

Rabies Immunoglobulin Indications

Rabies immunoglobulin (RIG) should be administered to all previously unvaccinated individuals with bite or nonbite exposures from animals suspected of having rabies, regardless of the interval between exposure and treatment initiation. 1, 2

Primary Indication

RIG is indicated for previously unvaccinated persons exposed to rabies through:

• Bite exposures: Any penetration of skin by teeth from a rabid or suspected rabid animal, regardless of wound location 1, 2
• Nonbite exposures: Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or potentially infectious material (such as brain tissue) from a rabid animal 1, 2
• Bat exposures: Any physical contact with bats when bite or mucous membrane contact cannot be excluded, as bat bites may be undetectable 2

The combination of RIG and vaccine is recommended for both bite and nonbite exposures, regardless of the interval between exposure and initiation of treatment. 1

Special Population: Immunocompromised Patients

Immunocompromised individuals require RIG at 20 IU/kg plus a 5-dose vaccine regimen (days 0,3,7,14, and 28), even if they were previously vaccinated. 3, 4 This is because immunosuppression substantially reduces vaccine response and standard schedules are inadequate. 4

Conditions requiring this enhanced regimen include:

• Corticosteroid therapy or other immunosuppressive medications 4
• HIV infection 4
• Chronic lymphoproliferative leukemia 4
• Other immunosuppressive illnesses 4

Critical Exclusion: Previously Vaccinated Persons

RIG should NOT be administered to previously vaccinated persons, as it will inhibit the anamnestic antibody response. 1, 3, 4 Previously vaccinated individuals are those who have completed a recommended preexposure or postexposure regimen with a cell culture vaccine (HDCV, RVA, or PCEC) or have documented rabies antibody titers. 1 These individuals require only 2 doses of vaccine (days 0 and 3). 1, 3, 4

Administration Specifications

RIG must be given at exactly 20 IU/kg body weight, administered only once at the beginning of prophylaxis. 1, 3, 4 The full calculated dose should be thoroughly infiltrated around and into all wounds if anatomically feasible, with any remaining volume injected intramuscularly at a site distant from vaccine administration. 1, 3, 4

Timing Window

If RIG was not administered when vaccination began, it can still be given through day 7 after the first vaccine dose. 1, 3, 2 Beyond day 7, RIG is not indicated for the same exposure since an antibody response to cell culture vaccine is presumed to have occurred. 1, 2

However, a new Category III exposure occurring after day 7 of an initial PEP series requires RIG administration, as this represents a separate exposure requiring immediate passive immunization. 5 The "no RIG after day 7" rule applies only to delayed administration for the same exposure, not to new exposures. 5

Critical Pitfalls to Avoid

• Never exceed 20 IU/kg dose of RIG, as higher doses can partially suppress active antibody production 1, 3, 4
• Never administer RIG in the same syringe or anatomical site as vaccine, as this may interfere with vaccine immunogenicity 3, 4
• Never give RIG to previously vaccinated persons, as this is a critical error that suppresses the memory immune response 3, 4
• Never withhold RIG based on time elapsed since exposure – treatment should begin immediately upon recognition of exposure, even if weeks or months have passed 3, 4

Exposure Assessment Algorithm

To determine if RIG is indicated, evaluate:

1. Vaccination history: Has the person completed a full rabies vaccine series? If yes, RIG is contraindicated. 1, 3

2. Immune status: Is the person immunocompromised? If yes, RIG is required even if previously vaccinated. 3, 4

3. Exposure type: Was there skin penetration, mucous membrane contact, or contamination of open wounds with saliva/neural tissue? If no exposure occurred, neither RIG nor vaccine is needed. 1

4. Animal species and status: High-risk animals (bats, skunks, foxes, coyotes, raccoons, bobcats) should be regarded as rabid unless proven negative by laboratory testing. 2

The FDA label confirms that RIG is recommended for treatment of all bites by animals suspected of having rabies and for nonbite exposures inflicted by animals suspected of being rabid. 2 A combination of active and passive immunization is considered acceptable postexposure prophylaxis except for persons who have been previously immunized with documented adequate rabies antibody titer. 2

Human rabies immunoglobulin is preferred over equine antirabies serum when available. 2