What is the recommended pre-exposure prophylaxis (PEP) schedule for rabies?

Recommended Pre-Exposure Prophylaxis Schedule for Rabies

The recommended pre-exposure prophylaxis schedule for rabies consists of three 1.0-mL doses of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) administered intramuscularly in the deltoid area on days 0,7, and 21 or 28. 1

Primary Vaccination Series

• The primary vaccination series consists of three 1.0-mL injections of HDCV or PCECV administered intramuscularly in the deltoid area 1
• The schedule follows a specific timeline: first dose on day 0, second dose on day 7, and third dose on either day 21 or day 28 1
• Vaccine preparations for intradermal administration are no longer available in the United States 1
• This three-dose regimen establishes adequate immunity against rabies virus and creates immunologic memory for future exposures 2, 3

Target Population for Pre-Exposure Prophylaxis

• Pre-exposure vaccination should be offered to persons in high-risk groups, including veterinarians and their staff, animal handlers, rabies researchers, and certain laboratory workers 1
• Individuals who frequently handle bats should receive pre-exposure prophylaxis regardless of their location, as lyssaviruses exist on all continents except Antarctica 1
• International travelers should consider pre-exposure vaccination if they are likely to come in contact with animals in rabies-endemic areas where immediate access to appropriate medical care might be limited 1, 4
• Routine pre-exposure prophylaxis is not recommended for the general U.S. population or routine travelers to areas where rabies is not enzootic 1

Booster Dose Recommendations Based on Risk Category

• Continuous Risk (laboratory workers, vaccine production facilities):

  • Serum should be tested for rabies virus neutralizing antibody every 6 months 1, 2
  • Booster dose required if serum titer falls below complete neutralization at a 1:5 serum dilution by RFFIT 1, 2

• Frequent Risk (diagnostic lab workers, cavers, veterinarians, animal control officers in enzootic areas):

  • Serum should be tested for rabies virus neutralizing antibody every 2 years 1, 2
  • Booster dose required if titer is less than complete neutralization at a 1:5 serum dilution by RFFIT 1, 2
  • Alternatively, a booster can be administered directly without testing 2, 5

• Infrequent Risk (veterinarians in low-prevalence areas, travelers who completed the primary series):

  • No routine serologic verification or booster doses required 1, 2
  • If exposed to rabies, they are considered immunologically primed and require only a simplified post-exposure regimen 1

Benefits of Pre-Exposure Prophylaxis

• Eliminates the need for rabies immunoglobulin (RIG) if exposed to rabies 1, 2, 3
• Reduces the number of vaccine doses needed for post-exposure prophylaxis from 4 to 2 doses 1, 2
• May provide partial immunity if post-exposure prophylaxis is delayed 1
• Provides protection against unrecognized exposures to rabies 1, 5
• A single booster dose after primary vaccination can provide long-term immunity in most individuals 5

Special Considerations

• Immunosuppressed individuals should postpone pre-exposure vaccinations when possible 1
• If vaccination cannot be postponed in immunosuppressed persons, antibody response should be checked after completing the pre-exposure series 1, 2
• If no acceptable antibody response is detected, the patient should be managed in consultation with their physician and appropriate public health officials 1, 2

Post-Vaccination Management

• For previously vaccinated persons who are subsequently exposed to rabies, only 2 IM doses of vaccine are required (on days 0 and 3), without RIG 1, 2
• Determining rabies virus neutralizing antibody titer for decision-making about post-exposure prophylaxis in previously vaccinated persons is unnecessary and could delay treatment 1

Human rabies is nearly 100% fatal once clinical symptoms develop, making proper pre-exposure prophylaxis crucial for high-risk individuals 3. Following the recommended three-dose schedule provides effective protection and simplifies management if exposure occurs.