What is the latest recommended rabies vaccination (post-exposure prophylaxis, PEP) schedule?

Latest Rabies Post-Exposure Prophylaxis Schedule

For previously unvaccinated individuals, administer 4 doses of rabies vaccine on days 0,3,7, and 14, combined with rabies immune globulin (20 IU/kg) on day 0. 1, 2

For Previously Unvaccinated Persons

Immediate Wound Care

• Thoroughly wash all wounds with soap and water for 15 minutes immediately upon presentation—this is perhaps the most effective single measure for preventing rabies and should precede all other interventions. 1, 3
• If available, irrigate wounds with a virucidal agent such as povidone-iodine solution after washing. 4, 2

Vaccine Regimen

• Administer 4 doses of HDCV (human diploid cell vaccine) or PCECV (purified chick embryo cell vaccine), 1.0 mL intramuscularly on days 0,3,7, and 14. 4, 1, 2
• Day 0 is defined as the day the first dose is administered, not necessarily the day of exposure. 1
• Inject in the deltoid muscle for adults and older children; use the anterolateral thigh for young children. 4, 1, 2
• Never administer vaccine in the gluteal area, as this produces inadequate antibody response. 4, 1, 5

This represents a reduction from the historical 5-dose schedule, which was changed in 2010 based on evidence demonstrating adequate immune response with 4 doses when combined with rabies immune globulin. 4, 6

Rabies Immune Globulin (HRIG) Administration

• Administer HRIG at 20 IU/kg body weight on day 0, ideally at the same time as the first vaccine dose. 1, 2, 5
• Infiltrate the full dose around and into the wound(s) if anatomically feasible; inject any remaining volume intramuscularly at a site distant from vaccine administration. 4, 1, 5
• Never administer HRIG in the same syringe or at the same anatomical site as the vaccine. 4, 2, 5
• Do not exceed the recommended 20 IU/kg dose, as excess HRIG may partially suppress active antibody production. 2, 5
• If HRIG was not given on day 0, it can still be administered up to and including day 7 of the vaccine series. 4, 1, 5

For Previously Vaccinated Persons

Previously vaccinated individuals require only 2 doses of vaccine (on days 0 and 3) and do NOT need HRIG. 4, 7

Definition of "Previously Vaccinated"

• Anyone who received a complete ACIP-recommended pre-exposure or post-exposure prophylaxis regimen with cell-culture vaccines (HDCV, PCECV, or RVA). 4, 7
• Anyone who received another vaccine regimen and has documented adequate rabies virus-neutralizing antibody response. 4, 7
• This applies regardless of how long ago the vaccination occurred. 7

Simplified Regimen

• Administer 1.0 mL intramuscularly in the deltoid on days 0 and 3 only. 4, 7
• HRIG should not be administered to avoid inhibiting the anamnestic immune response. 4, 7

Critical Special Populations

Immunocompromised Patients

Immunocompromised individuals must receive the full 5-dose vaccine regimen (days 0,3,7,14, and 28) plus HRIG at 20 IU/kg, even if previously vaccinated. 4, 1, 2, 7

• Conditions causing immunosuppression include: corticosteroid use, other immunosuppressive medications, antimalarials, HIV/AIDS, and other immunosuppressive illnesses. 7
• These patients should also undergo serologic testing 7-14 days after the final dose to confirm adequate antibody response. 2, 7

Pregnant Women

• Rabies vaccination during pregnancy is safe and effective; pregnancy is not a contraindication to PEP. 8

Young Children

• Children receive the same vaccine dose volume (1.0 mL) as adults. 4
• Use the anterolateral thigh for vaccine administration in young children. 4, 1

Timing Considerations

Urgency of Initiation

• Initiate PEP as soon as possible after exposure, ideally within 24 hours. 1, 5
• There is no absolute cutoff beyond which PEP should be withheld—treatment remains indicated even if weeks or months have elapsed since exposure, as rabies is nearly 100% fatal once clinical symptoms develop. 1, 2
• Delays of even a few hours matter significantly given the uniformly fatal outcome once the virus reaches the central nervous system. 1

Schedule Deviations

• Delays of a few days for individual doses are unimportant. 1
• For substantial deviations (weeks or more), assess immune status by serologic testing 7-14 days after the final dose. 1
• Most interruptions do not require restarting the entire series. 1

Common Pitfalls to Avoid

• Never use the gluteal area for vaccine administration—this is associated with vaccine failure due to inadequate immune response. 4, 1, 5
• Never exceed the recommended HRIG dose of 20 IU/kg—excess immunoglobulin suppresses active antibody production. 2, 5
• Never give HRIG to previously vaccinated persons—it will inhibit the anamnestic response. 4, 7
• Never forget to upgrade immunocompromised patients to the 5-dose regimen—the standard 4-dose schedule is inadequate for this population. 4, 2, 7
• Do not withhold PEP based on time elapsed since exposure—treatment can be successful even when initiated months after exposure if recognition was delayed. 1, 2

Efficacy

When administered promptly and appropriately, this PEP regimen combining wound care, HRIG infiltration, and the vaccine series is nearly 100% effective in preventing human rabies. 2