What is the post-exposure prophylaxis (PEP) protocol for rabies exposure?

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Rabies Post-Exposure Prophylaxis Protocol

Immediate Wound Management

All bite wounds and scratches must be immediately and thoroughly washed with soap and water for 15 minutes—this is perhaps the single most effective measure for preventing rabies infection. 1, 2, 3

  • After washing, irrigate the wound with a virucidal agent if available 2
  • This local wound treatment has been shown in animal studies to markedly reduce the likelihood of rabies infection 1, 3
  • Tetanus prophylaxis should be administered if the patient has not been vaccinated within the past 10 years 4

Post-Exposure Prophylaxis for Previously Unvaccinated Persons

For individuals who have never received rabies vaccination, administer both human rabies immune globulin (HRIG) and a 4-dose vaccine series on days 0,3,7, and 14. 1, 2

HRIG Administration

  • Dose: 20 IU/kg body weight, administered on day 0 (the day the first vaccine dose is given) 1, 2, 3
  • Infiltrate the full dose of HRIG around and into the wound(s) if anatomically feasible; any remaining volume should be administered intramuscularly at a site distant from the vaccine injection 2, 3
  • HRIG must never be administered in the same syringe or at the same anatomical site as the vaccine 2, 3
  • If HRIG was not given initially, it can still be administered up to and including day 7 after the first vaccine dose 2, 3
  • Do not exceed the 20 IU/kg dose, as excessive amounts may suppress active antibody production 2

Vaccine Administration

  • Use either human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1, 2
  • Dose: 1.0 mL per dose, administered intramuscularly 1, 2
  • Schedule: Days 0,3,7, and 14 (day 0 is the day the first dose is given, not necessarily the day of exposure) 1, 2
  • Inject in the deltoid muscle for adults and older children; use the anterolateral thigh for young children 1, 2
  • Never use the gluteal area—this produces inadequate antibody response and has been associated with vaccine failure 2, 3

Post-Exposure Prophylaxis for Previously Vaccinated Persons

Previously vaccinated individuals require only 2 doses of vaccine (on days 0 and 3) and do NOT need HRIG. 1, 2, 5

  • This applies to persons who have completed a recommended preexposure or postexposure vaccination regimen with a cell culture vaccine 1
  • The anamnestic immune response in previously vaccinated persons makes HRIG unnecessary and potentially inhibitory 1, 5
  • Immediate thorough wound washing remains essential 5

Special Population: Immunocompromised Patients

Immunocompromised patients require a 5-dose vaccine regimen (days 0,3,7,14, and 28) plus HRIG at 20 IU/kg on day 0, even if they were previously vaccinated. 2

  • This includes patients on corticosteroids, other immunosuppressive agents, antimalarials, or those with immunosuppressive illnesses (HIV, chronic lymphoproliferative leukemia) 2
  • Mandatory serologic testing must be performed 1-2 weeks after the final vaccine dose (day 42) using the rapid fluorescent focus inhibition test (RFFIT) 2
  • An acceptable antibody response is complete neutralization of challenge virus at a 1:5 serum dilution (≥0.5 IU/mL) 2, 6
  • If no adequate antibody response is detected, consult with public health officials for further management 2
  • Immunosuppressive medications should not be administered during PEP unless essential for other conditions 2

Critical Timing Considerations

Initiate PEP as soon as possible after exposure, ideally within 24 hours, though treatment remains indicated even if weeks or months have elapsed since exposure. 2, 7

  • Rabies is nearly 100% fatal once clinical symptoms develop, so delays of even hours matter significantly 2, 7
  • There is no absolute cutoff beyond which PEP should be withheld—once exposure is recognized, begin immediately regardless of time elapsed 2
  • The rabies incubation period typically ranges from 1-3 months but can extend beyond one year 2
  • When administered promptly and appropriately, PEP is nearly 100% effective in preventing human rabies 2, 7

Managing Schedule Deviations

  • Delays of a few days for individual doses are unimportant 2
  • For substantial deviations (weeks or more), assess immune status by serologic testing 7-14 days after the final dose 2
  • Most interruptions do not require restarting the entire series 2

Common Pitfalls to Avoid

  • Never administer vaccine in the gluteal area—this is associated with inadequate immune response and vaccine failure 2, 3
  • Never give HRIG to previously vaccinated persons—it will inhibit the anamnestic response 2
  • Never exceed the recommended HRIG dose of 20 IU/kg—excessive amounts suppress active antibody production 2
  • Do not forget that immunocompromised patients require the 5-dose regimen, not the standard 4-dose schedule 2
  • Do not administer HRIG and vaccine in the same syringe or anatomical site 2, 3

Exposure Risk Assessment

Rabies transmission requires virus introduction into bite wounds, open cuts in skin, or onto mucous membranes. 1, 3

Bite Exposures

  • Any penetration of skin by teeth constitutes a bite exposure requiring evaluation 1, 3
  • Bat bites can be minor and go undetected—consider PEP for any physical contact with bats when bite or mucous membrane contact cannot be excluded 3

Nonbite Exposures

  • Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or neural tissue from a rabid animal constitute nonbite exposures 1, 3
  • Casual contact (petting a rabid animal, contact with blood, urine, or feces) does not constitute exposure and is not an indication for prophylaxis 1, 3
  • If the material containing virus is dry, the virus is considered noninfectious 1, 3
  • Intact skin exposure to saliva does not warrant PEP 4

Animal Observation Protocol

A healthy domestic dog or cat that bites should be confined and observed daily for 10 days without administering rabies vaccine during the observation period. 4, 3

  • If the animal remains healthy throughout the 10-day observation period, PEP is not needed 3
  • If signs suggestive of rabies develop, the animal should be euthanized immediately and the head submitted for brain examination 4, 3
  • Stray or unwanted animals may be euthanized immediately and tested without observation 4, 3
  • Wild carnivores (skunks, bats, foxes, coyotes, raccoons, bobcats) and woodchucks should be regarded as rabid unless proven negative by laboratory testing 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Current Rabies Post-Exposure Prophylaxis Recommendations

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Dog Bite Management Follow-up

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Post-Exposure Prophylaxis for Previously Vaccinated Rabies Patients

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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