What are the clinical practice guidelines for post-exposure prophylaxis (PEP) in individuals exposed to rabies?

Rabies Post-Exposure Prophylaxis Guidelines

Immediate Wound Management

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

• Follow wound cleansing with irrigation using a virucidal agent such as povidone-iodine solution if available 1, 2
• Avoid suturing wounds when possible to prevent deeper viral inoculation 4
• Administer tetanus prophylaxis and bacterial infection control measures as indicated 3

Post-Exposure Prophylaxis for Previously Unvaccinated Persons

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

Vaccine Administration

• Use human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV), 1.0 mL per dose, administered intramuscularly 1, 2
• Inject in the deltoid muscle for adults and older children; use the anterolateral thigh for young children 1, 2, 4
• Never use the gluteal area for vaccine administration, as this produces inadequate antibody response and is associated with vaccine failure 1, 2, 4
• Day 0 is defined as the day the first dose is given, not necessarily the day of exposure 2

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, 4
• Infiltrate as much of the calculated dose as anatomically possible directly into and around all wound sites 1, 2, 4
• Any remaining HRIG volume should be administered intramuscularly at a site distant from vaccine administration 2, 4
• Do not administer HRIG and vaccine in the same syringe or at the same anatomical site 1, 2
• HRIG can be administered up to and including day 7 after the first vaccine dose if not given initially 2, 3
• Do not exceed the recommended HRIG dose of 20 IU/kg, as higher doses suppress active antibody production 1

Post-Exposure Prophylaxis for Previously Vaccinated Persons

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

• This applies to persons who have received recommended pre-exposure or postexposure regimens of HDCV, PCECV, or RVA, or those with documented rabies virus neutralizing antibody titer 5
• Administration of HRIG to previously vaccinated persons is contraindicated because passive antibody inhibits the anamnestic immune response 5, 1
• Do not check rabies virus neutralizing antibody titers for decision-making about prophylaxis in previously vaccinated persons, as several days are required for results, no protective titer is known, and other immune effectors beyond antibodies are operative 5

Special Populations: 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 previously vaccinated. 1, 2

• Corticosteroids, other immunosuppressive agents, antimalarials, and immunosuppressive illnesses (including HIV, chronic lymphoproliferative leukemia) substantially reduce immune responses to rabies vaccines 2
• Immunosuppressive agents should not be administered during rabies PEP unless essential for treatment of other conditions 2
• 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 (day 42 for immunocompromised patients) 2
• An acceptable antibody response is defined as complete neutralization at a 1:5 serum dilution by RFFIT 2
• If no acceptable antibody response is detected, manage the patient in consultation with their physician and public health officials 2

Pediatric Considerations

• Children receive the same vaccine dose volume (1.0 mL) and HRIG dose (20 IU/kg) as adults 1, 2
• Use the anterolateral thigh for vaccine administration in young children 1, 2

Critical Timing Considerations

Initiate PEP as soon as possible after exposure, ideally within 24 hours, although PEP should be administered regardless of time elapsed since exposure. 1, 2, 3

• Delays of even a few hours matter because rabies is nearly 100% fatal once clinical symptoms develop 2
• Treatment should begin immediately upon recognition of exposure, even if weeks or months have elapsed 2
• When administered promptly and appropriately, PEP is nearly 100% effective in preventing human rabies 2, 6
• Delays of a few days for individual doses are unimportant, though the effect of longer lapses is unknown 2
• For substantial schedule deviations, assess immune status by serologic testing 7-14 days after the final dose 2

Exposure Risk Assessment

Rabies transmission requires virus introduction into bite wounds, open cuts in skin, or onto mucous membranes. 2, 3

Bite Exposures

• Any penetration of skin by teeth constitutes a bite exposure requiring evaluation 2, 3
• Bites to the face and hands carry the highest risk, but site should not influence the decision to begin treatment 3
• For bat exposures: Consider PEP for any physical contact with bats when bite or mucous membrane contact cannot be excluded, as bat bites may be less severe and go completely undetected 3

Nonbite Exposures

• Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or neural tissue from a rabid animal constitute nonbite exposures 2, 3
• If the material containing virus is dry, the virus is considered noninfectious 2, 3
• Casual contact (petting a rabid animal, contact with blood, urine, or feces) does not constitute exposure and is not an indication for prophylaxis 3

Animal-Specific Considerations

High-Risk Animals

• Regard skunks, bats, foxes, coyotes, raccoons, bobcats, other carnivores, and woodchucks as rabid unless proven negative by laboratory testing 3
• These animals should be euthanized and tested as soon as possible; holding for observation is not recommended 3

Dogs and Cats

• If healthy and available for 10 days of observation, withhold treatment unless animal develops rabies 3
• Begin PEP at first sign of rabies during the observation period 3
• If rabid or suspected rabid, administer HRIG and vaccine immediately 3

Low-Risk Animals

• Bites from squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other rodents, rabbits, and hares almost never require PEP in most geographical areas 3
• Consult local and state public health officials for individual case assessment 3

Pre-Exposure Prophylaxis and Booster Recommendations

Continuous Risk Category (Laboratory Workers)

• Test serum for rabies virus neutralizing antibody every 6 months 5
• Administer IM booster dose if titer falls below complete neutralization at 1:5 serum dilution by RFFIT 5

Frequent Risk Category (Veterinarians, Animal Control Officers, Cavers)

• Test serum for rabies virus neutralizing antibody every 2 years 5
• Administer single booster dose if titer is less than complete neutralization at 1:5 serum dilution by RFFIT 5

Infrequent Exposure Group

• Veterinarians, veterinary students, and animal control officers in areas where rabies is uncommon do not require routine serologic verification or routine pre-exposure booster doses 5
• If exposed to rabies, they require only postexposure prophylaxis for previously vaccinated persons (days 0 and 3 vaccination) 5

Post-Vaccination Serologic Testing

• No testing of immunocompetent patients completing pre-exposure or postexposure prophylaxis is necessary to document seroconversion 5
• Immunosuppressed persons must have serologic testing performed after completing prophylaxis 5
• Patients who are immunosuppressed should postpone pre-exposure vaccinations and avoid activities requiring rabies prophylaxis when possible 5

Common Pitfalls to Avoid

• Never administer vaccine in the gluteal area - associated with inadequate immune response and vaccine failure 1, 2, 4
• Never give HRIG to previously vaccinated persons - inhibits the anamnestic immune response 5, 1
• Never administer HRIG and vaccine in the same syringe or anatomical location 1, 2
• Never exceed 20 IU/kg HRIG dose - higher doses suppress active antibody production 1
• Never skip wound cleansing - inadequate wound care is a critical error, as local wound treatment is the most effective single measure 4, 3
• Never delay PEP initiation while awaiting animal testing results - begin treatment immediately if indicated 5, 3
• Never use standard 4-dose regimen for immunocompromised patients - they require the 5-dose schedule 1, 2