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 body weight infiltrated around the wound plus a 4-dose rabies vaccine series on days 0,3,7, and 14. 1, 2

Immediate Wound Management

• Wash all bite wounds and scratches thoroughly with soap and water for approximately 15 minutes immediately after exposure – this single intervention markedly reduces rabies risk in animal studies and is perhaps the most effective preventive measure 1, 2, 3
• Irrigate wounds with a virucidal agent such as povidone-iodine solution if available 1, 2
• Administer tetanus prophylaxis and antibiotics as indicated for bacterial infection control 1, 2
• Avoid suturing wounds when possible 1

Post-Exposure Prophylaxis for Previously Unvaccinated Persons

Passive Immunization (HRIG)

• Administer HRIG at exactly 20 IU/kg body weight as a single dose on day 0 2, 4
• Infiltrate the full dose of HRIG thoroughly around and into all wounds if anatomically feasible – any remaining volume should be injected intramuscularly at a site distant from the vaccine injection 2, 4
• HRIG can be administered through day 7 after the first vaccine dose – beyond day 7, HRIG is not indicated since an antibody response to vaccine is presumed to have occurred 3

Active Immunization (Vaccine)

• Administer rabies vaccine (HDCV, PCECV, or RVA) as a 4-dose series on days 0,3,7, and 14 1, 2
• This represents an updated recommendation from the previous 5-dose regimen that was used prior to 2010 1
• Administer vaccine intramuscularly in the deltoid muscle for adults and older children – in infants and small children, use the anterolateral aspect of the thigh 4
• Never administer vaccine in the gluteal area – this results in lower neutralizing antibody titers 2

Post-Exposure Prophylaxis for Previously Vaccinated Persons

Previously vaccinated individuals require only 2 doses of rabies vaccine on days 0 and 3, without HRIG. 5, 2

• Do not administer HRIG to previously vaccinated persons – it may blunt the rapid anamnestic antibody response 5, 2
• "Previously vaccinated" means persons who have ever received a complete pre-exposure or post-exposure vaccination regimen with a cell culture vaccine, or those with a previously documented rabies virus neutralizing antibody titer 1, 5
• Previously vaccinated individuals develop a rapid anamnestic immune response, with studies showing adequate antibody titers maintained at 1 year post-vaccination 5

Special Populations

Immunosuppressed Patients

• Immunosuppressed patients should receive the full 5-dose vaccination regimen (days 0,3,7,14, and 28) with HRIG 5
• This represents a critical exception to the standard 4-dose protocol 5

Timing and Urgency

• PEP is a medical urgency, not a medical emergency – decisions should be made promptly but consultation should not delay treatment 1, 6, 2
• Administer PEP regardless of delay, even months after exposure, provided the person shows no clinical signs of rabies 1, 6, 2
• Incubation periods exceeding 1 year have been documented in humans, making delayed treatment still effective 1, 6
• Initiate PEP as soon as possible after exposure, ideally within 24 hours 6, 3

Efficacy and Outcomes

• The combination of wound care, HRIG, and vaccine is nearly 100% effective when properly administered 1, 2, 7, 8
• No failures have been documented in the United States since current cell culture biologics were licensed, despite occasional improper administration 1, 2
• Once clinical symptoms of rabies appear, the disease is almost universally fatal – only 6 documented human survivors exist, and 5 had received pre-symptom vaccination 2

When to Discontinue PEP

• If laboratory testing (direct fluorescent antibody test) confirms the exposing animal was not rabid, discontinue PEP 1, 4, 3
• For healthy dogs, cats, or ferrets available for observation: if the animal remains healthy throughout a 10-day observation period, PEP is not needed 6, 4, 3
• If the animal dies or is killed before completing the 10-day observation period, initiate PEP immediately 6

Critical Pitfalls to Avoid

• Never delay PEP waiting for animal testing results – begin treatment immediately for high-risk exposures (bats, raccoons, skunks, foxes) 6, 4
• Do not administer HRIG to previously vaccinated persons 5, 2
• Do not inject vaccine in the gluteal region 2
• Do not withhold PEP due to time elapsed since exposure 1, 6, 2
• For bat exposures, consider PEP for any physical contact when bite or mucous membrane contact cannot be excluded – bat bites may be less severe and go completely undetected 3