How long after an animal bite must rabies post‑exposure prophylaxis (PEP) be initiated?

Rabies Post-Exposure Prophylaxis Must Be Initiated Immediately After Recognition of Exposure

Rabies post-exposure prophylaxis (PEP) should be started as soon as possible after an animal bite—ideally within 24 hours—but there is no absolute time cutoff beyond which treatment should be withheld. 1, 2 Even if weeks or months have elapsed since the exposure, PEP remains indicated as long as clinical symptoms of rabies have not yet appeared, because the incubation period can range from days to over one year. 1, 2

Critical Timing Principles

• Administration of PEP is a medical urgency, not a medical emergency, but decisions must not be delayed. 1 Once rabies symptoms develop, the disease is nearly 100% fatal, making immediate initiation upon recognition of exposure essential. 2, 3

• The sooner treatment begins after exposure, the better the outcome. 4 Delays of even a few hours matter significantly because the virus travels along peripheral nerves toward the central nervous system, and early intervention can prevent this progression. 2

• When a documented or likely exposure has occurred, PEP should be administered regardless of the length of delay, provided that compatible clinical signs of rabies are not present in the exposed person. 1 The administration of PEP to a clinically rabid patient has demonstrated consistent ineffectiveness. 1

The Complete PEP Protocol

Immediate Wound Management (Within Minutes)

• Thoroughly wash all wounds with soap and water for at least 15 minutes immediately after exposure—this is perhaps the single most effective measure for preventing rabies infection. 1, 2, 4, 5 Animal studies demonstrate that local wound treatment markedly reduces the likelihood of rabies infection. 2

• Follow wound washing with irrigation using a virucidal agent such as povidone-iodine solution if available. 2, 4

• Assess tetanus immunization status and provide tetanus prophylaxis when indicated; administer antibiotics as needed to control bacterial infection. 6, 4

For Previously Unvaccinated Persons (Standard Regimen)

The complete regimen consists of human rabies immune globulin (HRIG) plus a 4-dose vaccine series: 1, 2, 4

Human Rabies Immune Globulin (HRIG)

• Administer HRIG at exactly 20 IU/kg body weight on day 0 (the day the first vaccine dose is given), ideally simultaneously with the first vaccine dose. 2, 4 This dose applies to all ages, including children. 2

• Infiltrate the full calculated dose of HRIG around and into all wounds if anatomically feasible; inject any remaining volume intramuscularly at a site distant from vaccine administration. 2, 4 Local wound infiltration is essential for neutralizing virus at the exposure site. 2

• HRIG can be administered up to and including day 7 after the first vaccine dose if it was not given initially. 1, 2, 6 Beyond day 7, do NOT administer HRIG because vaccine-induced antibodies are presumed to have developed, and additional passive antibody may suppress active antibody production. 2, 6

• Never administer HRIG in the same syringe or at the same anatomical site as the vaccine. 2, 4

• Do not exceed 20 IU/kg—higher doses partially suppress active antibody production from the vaccine. 2, 4

Rabies Vaccine Series

• Administer 4 doses of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV), 1.0 mL per dose, intramuscularly on days 0,3,7, and 14. 1, 2, 4 Day 0 is defined as the day the first dose is given, not necessarily the day of exposure. 2

• Inject in the deltoid muscle for adults and older children; use the anterolateral thigh for young children. 2, 4 Children receive the same vaccine dose volume (1.0 mL) as adults. 2

• Never use the gluteal area for vaccine administration—this produces inadequate antibody response and has been associated with vaccine failures. 2, 4

For Previously Vaccinated Persons

• Administer only 2 doses of vaccine on days 0 and 3; do NOT give HRIG. 1, 2, 4 HRIG will inhibit the anamnestic (memory) antibody response in previously vaccinated individuals. 2, 6

• This simplified regimen applies to anyone who has completed a recommended pre-exposure or post-exposure vaccination series with a cell culture vaccine and has documented antibody response. 2, 4

For Immunocompromised Patients

• Administer a 5-dose vaccine regimen on days 0,3,7,14, and 28, plus HRIG at 20 IU/kg on day 0, even if previously vaccinated. 1, 2 Immunosuppression (from corticosteroids, other immunosuppressive agents, antimalarials, HIV infection, or immunosuppressive illnesses) substantially reduces vaccine response. 2

• Mandatory serologic testing for rabies virus-neutralizing antibody by rapid fluorescent focus inhibition test (RFFIT) must be performed 1-2 weeks after the final vaccine dose. 2 An acceptable antibody response is complete neutralization of challenge virus at a 1:5 serum dilution. 2

• If no acceptable antibody response is detected, manage the patient in consultation with their physician and public health officials. 2

Efficacy and Real-World Outcomes

• When administered promptly and appropriately, PEP combining wound care, HRIG infiltration, and the vaccine series is nearly 100% effective in preventing human rabies. 1, 2, 3 No failures have been documented in the United States since current biologics have been licensed when the protocol is properly followed. 1, 2

• All immunocompetent individuals completing the 4-dose schedule achieve neutralizing antibody titers ≥0.5 IU/mL by day 14. 2

• Even incomplete series (3-4 doses) have prevented rabies in exposed individuals. 2 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. 2

Schedule Flexibility and Practical Considerations

• Delays of a few days for individual doses are unimportant and do not compromise protection. 2, 6 The effect of longer lapses of weeks or more is unknown, but most interruptions do not require restarting the entire series. 2

• For substantial deviations, immune status should be assessed by serologic testing 7-14 days after the final dose. 2

• If PEP has been initiated and subsequent immunofluorescence testing shows that the exposing animal was not rabid, PEP can be discontinued. 1, 4

Common Pitfalls to Avoid

• Do not withhold treatment while waiting for animal observation results if the exposure occurred in a rabies-endemic area—treatment can be discontinued if the animal remains healthy after 10 days. 2

• Do not delay treatment for serologic testing in previously unvaccinated persons—routine post-vaccination antibody testing is unnecessary in immunocompetent individuals. 2

• Do not give HRIG to previously vaccinated persons—this is a critical error that suppresses the memory immune response. 2

• Do not administer vaccine in the gluteal area—this is associated with vaccine failure due to inadequate immune response. 2, 4

• Do not exceed the recommended HRIG dose of 20 IU/kg—higher amounts suppress active antibody production. 2, 4