What are the recommended rabies vaccine regimens for pre‑exposure prophylaxis in high‑risk individuals (e.g., veterinarians, animal‑care workers, laboratory staff, travelers to endemic areas) and for post‑exposure prophylaxis after a bite or mucosal exposure, including dosing schedule, use of rabies immune globulin, and special considerations for immunocompromised patients?

Rabies Vaccination: Pre-Exposure and Post-Exposure Prophylaxis

For high-risk individuals requiring pre-exposure prophylaxis, administer three 1.0-mL doses of HDCV or PCECV intramuscularly in the deltoid on days 0,7, and 21 or 28; for post-exposure prophylaxis in previously unvaccinated persons, immediately initiate wound cleansing followed by rabies immune globulin (20 IU/kg infiltrated into wounds) plus four vaccine doses on days 0,3,7, and 14. 1, 2, 3

Pre-Exposure Prophylaxis

Who Should Receive Pre-Exposure Vaccination

High-risk groups requiring pre-exposure prophylaxis include: 1

• Veterinarians and their staff
• Animal handlers and animal control officers
• Rabies researchers and laboratory workers handling rabies virus
• Cave explorers (spelunkers) who may encounter bats
• Travelers spending ≥1 month in rabies-endemic areas where immediate access to appropriate medical care and biologics may be limited
• Persons who frequently handle bats, regardless of geographic location

Pre-exposure prophylaxis is NOT recommended for the general U.S. population or routine travelers to areas where rabies is not enzootic. 1

Pre-Exposure Vaccination Schedule

Primary vaccination consists of three 1.0-mL injections of HDCV or PCECV administered intramuscularly in the deltoid area on days 0,7, and 21 or 28. 1, 4

For infants and young children, the anterolateral thigh is acceptable. 4

Never administer vaccine in the gluteal area—this produces inadequate antibody response and has been associated with vaccine failures. 1, 2, 4

Booster Dose Requirements by Risk Category

Continuous risk category (laboratory workers handling live rabies virus in research/vaccine production): 1

• Check rabies antibody titers every 6 months
• Administer booster dose if titer falls below 1:5 dilution by RFFIT

Frequent risk category (diagnostic laboratory workers, cavers, veterinarians/staff, animal control officers in enzootic areas, bat handlers): 1

• Check antibody titers every 2 years
• Administer single booster dose if titer is inadequate (<1:5 dilution)

Infrequent risk category (veterinarians/students in low-endemicity areas, certain international travelers who completed full pre-exposure series): 1

• No routine serologic testing or booster doses required
• If exposed, receive simplified post-exposure regimen (2 doses only)

Post-Exposure Prophylaxis for Previously Unvaccinated Persons

Immediate Wound Management

Thoroughly wash all bite wounds and scratches with soap and water for at least 15 minutes—this is the single most effective measure for preventing rabies. 1, 2, 3

Follow with irrigation using a virucidal agent such as povidone-iodine solution if available. 1, 2, 3

Administer tetanus prophylaxis and antibiotics as indicated to prevent secondary bacterial infection. 1, 2

Avoid suturing large wounds unless required for cosmetic reasons or high risk of bacterial infection. 2

Rabies Immune Globulin (RIG) Administration

Administer human RIG at exactly 20 IU/kg body weight on day 0, ideally simultaneously with the first vaccine dose. 1, 2, 3, 4

Infiltrate the full calculated dose around and into all wounds if anatomically feasible; inject any remaining volume intramuscularly at a site distant from vaccine administration. 1, 2, 3, 4

Critical pitfalls to avoid: 1, 2, 3

• Never administer RIG in the same syringe or at the same anatomical site as the vaccine
• Never exceed 20 IU/kg—higher doses suppress active antibody production
• RIG can be administered up to and including day 7 if initially missed, but NOT beyond day 7 (vaccine-induced antibodies are presumed present by then)

Vaccine Schedule

Administer four 1.0-mL doses of HDCV or PCECV intramuscularly on days 0,3,7, and 14. 2, 3, 4, 5, 6

Day 0 is defined as the day the first dose is given, not necessarily the exposure date. 2, 3

Inject in the deltoid muscle for adults and older children; use the anterolateral thigh for young children. 1, 2, 3, 4

Never use the gluteal area—this produces inadequate antibody response and vaccine failure. 1, 2, 3, 4

Timing Considerations

Initiate post-exposure prophylaxis as soon as possible after exposure, ideally within 24 hours. 2, 3

However, there is no absolute cutoff—treatment should begin immediately upon recognition of exposure even if weeks or months have elapsed, as rabies incubation can exceed one year and the disease is uniformly fatal once symptoms appear. 2, 3

Delays of a few days for individual vaccine doses are acceptable and do not compromise protection; substantial delays of weeks warrant serologic testing 7-14 days after the final dose. 2, 3

Post-Exposure Prophylaxis for Previously Vaccinated Persons

Previously vaccinated individuals (those who completed a recommended pre-exposure or post-exposure regimen with cell culture vaccine) require only two 1.0-mL doses of vaccine intramuscularly on days 0 and 3. 1, 2, 3, 4

RIG is NOT administered to previously vaccinated persons—it will inhibit the anamnestic antibody response. 1, 2, 3, 4

This simplified regimen eliminates the need for RIG and reduces the number of vaccine doses from four to two. 1

Special Considerations for Immunocompromised Patients

Immunocompromised patients require a five-dose vaccine regimen on days 0,3,7,14, and 28, plus RIG at 20 IU/kg on day 0, even if previously vaccinated. 2, 3

Conditions requiring the 5-dose regimen include: 2, 3

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

Mandatory serologic testing is required 1-2 weeks after the final vaccine dose (day 42) to confirm adequate antibody response (≥1:5 dilution by RFFIT). 2, 3

If antibody response is inadequate, manage in consultation with the patient's physician and public health officials. 2, 3

Avoid administering immunosuppressive agents during rabies post-exposure prophylaxis unless essential for treatment of other conditions. 2, 3

Pregnancy Considerations

Pregnancy is NOT a contraindication to either pre-exposure or post-exposure rabies prophylaxis—the benefits of preventing rabies far outweigh theoretical risks to the fetus. 2

Efficacy of Post-Exposure Prophylaxis

When administered promptly and appropriately, the combination of wound care, RIG infiltration, and the vaccine series is nearly 100% effective in preventing human rabies. 2, 3, 5, 7, 6

No post-exposure prophylaxis failures have occurred in the United States since modern cell culture vaccines and human RIG have been routinely used. 1

Failures abroad have occurred only when deviations were made from the recommended protocol: 1

• Inadequate wound cleansing
• Vaccine administered in gluteal area instead of deltoid
• Inadequate RIG infiltration around wound sites
• Substantial delays in initiating prophylaxis, especially with severe face/head wounds

Common Pitfalls and How to Avoid Them

Never use the gluteal area for vaccine administration—this is the most common cause of vaccine failure. 1, 2, 3, 4

Do not give RIG to previously vaccinated persons—this suppresses the memory immune response. 1, 2, 3

Do not exceed 20 IU/kg of RIG—higher doses suppress active antibody production. 1, 2, 3

Do not delay treatment while waiting for animal observation results in endemic areas—treatment can be discontinued if the animal remains healthy after 10 days. 2, 3

Recognize that bat bites may be minor and undetected—maintain high suspicion for bat exposures. 2

For immunocompromised patients, do not use the standard 4-dose schedule—upgrade to the 5-dose regimen with mandatory serologic testing. 2, 3