Anti-Rabies Vaccine Dosing
For post-exposure prophylaxis in previously unvaccinated immunocompetent individuals, administer 4 doses of rabies vaccine (1.0 mL intramuscularly) on days 0,3,7, and 14, combined with human rabies immune globulin (HRIG) at 20 IU/kg on day 0. 1, 2, 3
Post-Exposure Prophylaxis (PEP) Regimens
Previously Unvaccinated Immunocompetent Patients
Vaccine schedule: 4 doses of HDCV or PCECV, 1.0 mL each, administered intramuscularly on days 0,3,7, and 14 (day 0 is the day the first dose is given, not necessarily the exposure date). 1, 2, 3
HRIG administration: 20 IU/kg body weight on day 0, infiltrated around and into the wound(s) if anatomically feasible, with any remaining volume given intramuscularly at a site distant from vaccine administration. 1, 2, 3
Injection sites: Deltoid muscle for adults and older children; anterolateral thigh for young children. Never use the gluteal area as it produces inadequate antibody response and vaccine failure. 1, 2, 3
Critical timing: HRIG can be administered up to and including day 7 if initially missed, but not beyond day 7 as vaccine-induced antibodies are presumed present. 2
Previously Vaccinated Immunocompetent Patients
Simplified regimen: Only 2 doses of vaccine (1.0 mL each) on days 0 and 3. 4, 1, 3
No HRIG required: HRIG should not be administered to previously vaccinated persons as it inhibits the anamnestic antibody response. 4, 1
Definition: Previously vaccinated means completion of an ACIP-recommended pre- or post-exposure prophylaxis regimen with cell-culture vaccines, or another regimen with documented adequate rabies virus-neutralizing antibody response. 4
Immunocompromised Patients (Critical Modification)
Extended vaccine schedule: 5 doses on days 0,3,7,14, and 28, regardless of prior vaccination status. 4, 1, 2, 3
HRIG still required: 20 IU/kg on day 0, even if previously vaccinated. 1, 2
Rationale: Corticosteroids, other immunosuppressive agents, antimalarials, HIV infection, and immunosuppressive illnesses substantially reduce immune responses to rabies vaccines. 4
Mandatory serologic testing: One or more serum samples must be tested for rabies virus-neutralizing antibody by RFFIT 1-2 weeks after the final vaccine dose to ensure adequate response (≥1:5 serum dilution). 4, 2
Inadequate response management: If no acceptable antibody response is detected, manage in consultation with the patient's physician and public health officials. 4
Pre-Exposure Prophylaxis (PrEP) Regimens
Standard Intramuscular Schedule
Three-dose regimen: 1.0 mL intramuscularly on days 0,7, and 21 or 28 for persons at continuous or frequent risk (laboratory workers, veterinarians, animal control officers, cavers, bat handlers). 2, 5, 6
Immunocompromised considerations: If possible, postpone PrEP until the immunocompromising condition resolves; if not possible, check virus-neutralizing antibody responses after completing the series. 4
Intradermal Administration (Alternative Route)
Two-site intradermal schedule: 2 × 0.1 mL doses on days 0 and 7 (2IDx2 schedule) or 1 × 0.1 mL doses on days 0,7, and 21-28 (1IDx3 schedule). 7, 8
Efficacy comparison: The 1IDx3 schedule achieved 93.4% seroconversion after primary course, with 98.7% seropositive post-booster, making it the most effective intradermal schedule, particularly in older travelers (>50 years). 7
One-week accelerated schedule: Two 0.1 mL intradermal doses on days 0 and 7 provided efficacious priming with 96.7-97.2% seroconversion rates 14 days post-last injection, enabling rapid anamnestic responses to simulated PEP one year later. 8
Route comparison: Generally no significant differences in seroconversion between 2-site intradermal and intramuscular administration, though two-dose IM schedules showed lower maintenance of seroconversion long-term than three-dose IM schedules. 9
Critical Administration Principles
HRIG Dosing Pitfalls
Never exceed 20 IU/kg: Higher doses partially suppress active antibody production from the vaccine. 1, 2, 3
Never co-administer: HRIG must not be given in the same syringe or at the same anatomical site as the vaccine. 1, 2, 3
Never give to previously vaccinated immunocompetent patients: This suppresses the memory immune response. 4, 1
Wound Care (First Priority)
Immediate thorough washing: All wounds with soap and water for 15 minutes before any biologicals are administered—this is the single most effective measure for preventing rabies. 1, 2, 3
Virucidal irrigation: Follow with povidone-iodine solution if available. 1, 2
Timing Flexibility
Initiate immediately: PEP should begin as soon as possible after exposure, ideally within 24 hours, but there is no absolute cutoff—treatment remains indicated even weeks or months after exposure. 1, 2
Schedule delays: Delays of a few days for individual doses are unimportant; missed doses should be administered immediately when the patient presents, resuming the schedule with the same intervals. 1, 2
Efficacy and Outcomes
Near-perfect effectiveness: When administered promptly and appropriately, the PEP regimen combining wound care, HRIG infiltration, and the vaccine series is nearly 100% effective in preventing human rabies. 1, 2, 3
No documented failures: Since modern cell-culture vaccines and HRIG were licensed in the United States, no failures of post-exposure prophylaxis have been reported when the protocol is followed correctly. 2
Incomplete regimens: Over 1,000 persons annually in the United States receive only 3 or 4 doses instead of the complete regimen, with no documented cases of rabies developing, even when >30% had confirmed exposure to rabid animals. 2