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

Rabies Post-Exposure Prophylaxis (PEP)

For previously unvaccinated individuals exposed to rabies, immediately administer both human rabies immune globulin (HRIG) at 20 IU/kg and a 4-dose rabies vaccine series on days 0,3,7, and 14, along with thorough wound cleansing. 1

Immediate Wound Management

• Wash all bite wounds and scratches immediately and thoroughly with soap and water for 15 minutes—this is the single most effective measure for preventing rabies infection. 2, 1, 3
• Apply a virucidal agent (such as povidone-iodine solution) to the wound if available, as this markedly reduces the likelihood of rabies in animal studies. 2, 1
• Administer tetanus prophylaxis and bacterial infection control measures as indicated. 2, 3
• Avoid suturing wounds when possible to allow drainage. 2

Post-Exposure Prophylaxis for Previously Unvaccinated Persons

Passive Immunization (HRIG)

• Administer HRIG at 20 IU/kg body weight on day 0, ideally at the same time as the first vaccine dose. 1, 4
• Infiltrate the full dose of HRIG around and into the wound(s) if anatomically feasible; inject any remaining volume intramuscularly at a site distant from the vaccine administration site. 1, 3
• HRIG should never be administered in the same syringe or at the same anatomical site as the vaccine. 1, 4
• HRIG can be administered up to and including day 7 after the first vaccine dose if it was not given initially; beyond day 7, HRIG is not indicated as an antibody response to the vaccine is presumed to have occurred. 1, 3

Active Immunization (Vaccine)

• Administer 4 doses of rabies vaccine (HDCV or PCECV), 1.0 mL intramuscularly on days 0,3,7, and 14. 1, 4
• Day 0 is defined as the day the first dose is given, not necessarily the day of exposure. 1
• Inject the vaccine in the deltoid muscle for adults and older children, or in the anterolateral thigh for young children. 1, 4
• Never administer the vaccine in the gluteal area, as this produces inadequate antibody response and is associated with vaccine failure. 1, 4

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, 5, 4
• This applies to persons who have completed a recommended pre-exposure or post-exposure vaccination regimen with a cell culture vaccine. 5, 4
• Previously vaccinated individuals develop a rapid anamnestic immune response upon re-exposure. 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
• Corticosteroids, other immunosuppressive agents, antimalarials, and immunosuppressive illnesses (including HIV) substantially reduce immune responses to rabies vaccines. 1
• Serologic testing for rabies virus-neutralizing antibody must be performed 1-2 weeks after the final vaccine dose to confirm adequate antibody response. 1
• An acceptable antibody response is defined as complete neutralization of challenge virus at a 1:5 serum dilution. 1
• Immunosuppressive agents should not be administered during rabies PEP unless essential for treatment of other conditions. 1

Timing and Urgency

• Rabies PEP is a medical urgency, not a medical emergency—decisions must not be delayed, but there is time for proper assessment. 2
• PEP should be initiated as soon as possible after exposure, ideally within 24 hours, though treatment remains indicated even if weeks or months have elapsed since exposure. 1, 3, 6
• Incubation periods of more than 1 year have been reported in humans; therefore, PEP should be administered regardless of the length of delay, provided that compatible clinical signs of rabies are not present in the exposed person. 2, 7
• Delays of a few days for individual doses are unimportant, though the effect of longer lapses is unknown. 1

Exposure Risk Assessment

Types of Exposure Requiring PEP

• Bite exposures: Any penetration of skin by teeth constitutes a bite exposure requiring evaluation. 1, 3
• Nonbite exposures: Scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or neural tissue from a rabid animal. 1, 3
• Bat exposures: PEP should be considered 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
• If the material containing virus is dry, the virus is considered noninfectious. 1, 3
• Casual contact (petting a rabid animal) or contact with blood, urine, or feces does not constitute an exposure and is not an indication for prophylaxis. 3

Animal-Specific Recommendations

• Dogs, cats, and ferrets: If healthy and available for 10-day observation, no PEP is needed unless the animal develops clinical signs of rabies during observation. 7, 3, 4
• If the animal dies or is killed before the 10-day observation period is complete, PEP should be initiated immediately, as the observation approach is no longer valid. 7
• Wild carnivores (skunks, raccoons, bats, foxes, coyotes): Regard as rabid unless proven negative by laboratory testing; initiate PEP immediately. 3, 4
• Rodents and lagomorphs (rabbits, hares): Bites from squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, and rabbits almost never require PEP. 3

Common Pitfalls to Avoid

• Do not administer HRIG to previously vaccinated persons, as it will inhibit the anamnestic response. 1
• Do not exceed the recommended HRIG dose of 20 IU/kg, as this may suppress active antibody production. 1
• Do not use the gluteal area for vaccine administration—this is associated with vaccine failure. 1, 4
• Do not forget to upgrade immunocompromised patients to the 5-dose regimen, as the standard 4-dose schedule is inadequate for this population. 1
• Do not delay PEP while waiting for animal testing results if the animal is a high-risk species or unavailable for observation. 2, 3

Efficacy

• When administered promptly and appropriately, rabies PEP is nearly 100% effective in preventing human rabies. 1, 6, 8
• No failures have been documented in the United States since current biologics have been licensed, when PEP has been properly administered. 2
• Once clinical manifestations of rabies develop, treatment options are extremely limited, and the disease is almost universally fatal. 6, 8