What are the recommended post‑exposure rabies prophylaxis guidelines, including wound cleansing, human rabies immune globulin (HRIG) dosing, and vaccine schedule for immunocompetent, immunocompromised, previously vaccinated, and pregnant patients?

Post-Exposure Rabies Prophylaxis Guidelines

For previously unvaccinated immunocompetent individuals exposed to rabies, immediately wash all wounds with soap and water for 15 minutes, then administer human rabies immune globulin (HRIG) at 20 IU/kg infiltrated into and around wounds on day 0, plus a 4-dose rabies vaccine series (1.0 mL intramuscularly) on days 0,3,7, and 14 in the deltoid muscle (or anterolateral thigh in young children). 1, 2

Immediate Wound Management

• Thorough wound cleansing with soap and water for at least 15 minutes is the single most effective measure to prevent rabies infection and must be performed before any other intervention. 1, 2, 3
• Follow wound washing with irrigation using a virucidal agent such as povidone-iodine solution if available. 2, 3
• Assess tetanus immunization status and provide tetanus prophylaxis when indicated. 2, 4
• Avoid suturing large rabies-exposed wounds whenever possible unless required for cosmetic reasons or high risk of bacterial infection. 4

Human Rabies Immune Globulin (HRIG) Administration

• Administer HRIG at exactly 20 IU/kg body weight on day 0, ideally simultaneously with the first vaccine dose. 1, 2
• Infiltrate the full calculated dose around and into all wounds if anatomically feasible; inject any remaining volume intramuscularly at a site distant from vaccine administration. 1, 2, 3
• Never administer HRIG in the same syringe or at the same anatomical site as the vaccine. 1, 2, 3
• Do not exceed 20 IU/kg—higher doses suppress active antibody production from the vaccine. 1, 2, 4
• HRIG can be administered up to and including day 7 after the first vaccine dose if initially missed, but must not be given after day 7 because vaccine-induced antibodies are presumed to be present. 1, 2, 4

Rabies Vaccine Schedule

Previously Unvaccinated Immunocompetent Persons

• Administer 4 doses of human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV), 1.0 mL intramuscularly on days 0,3,7, and 14. 1, 2, 3, 5
• Day 0 is defined as the day the first dose is administered, not necessarily the day of exposure. 2, 3
• Inject in the deltoid muscle for adults and older children; use the anterolateral thigh for young children. 1, 2, 3
• Never use the gluteal area for vaccine administration—this produces inadequate antibody response and has been associated with vaccine failures. 1, 2, 3

Previously Vaccinated Immunocompetent Persons

• Administer only 2 doses of vaccine on days 0 and 3; do NOT give HRIG. 1, 2, 4
• 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 adequate antibody response. 1, 2, 4
• HRIG should never be given to previously vaccinated persons—it will inhibit the anamnestic (memory) antibody response. 2, 4, 3

Immunocompromised Patients (Regardless of Prior Vaccination)

• 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. 2, 4, 3
• Immunosuppressive conditions include corticosteroid use, other immunosuppressive agents, antimalarials, HIV infection, chronic lymphoproliferative leukemia, and other immunosuppressive illnesses. 2, 4
• 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, 4
• 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
• Immunosuppressive agents should not be administered during rabies post-exposure prophylaxis unless essential for treatment of other conditions. 2

Pre-Exposure Prophylaxis

• Administer three 1.0 mL injections of HDCV or PCECV intramuscularly on days 0,7, and 21 or 28. 1, 2
• Pre-exposure immunization is recommended for high-risk groups: animal handlers, laboratory workers, field personnel, persons spending more than 1 month in rabies-endemic areas, and those whose vocations or avocations bring them into contact with potentially rabid animals. 1, 2
• Persons with continuing risk should receive a booster dose every 2 years or have serum tested for rabies antibody every 2 years and receive a booster if the titer is inadequate. 1

Timing and Efficacy

• Post-exposure prophylaxis is a medical urgency, not a medical emergency, but decisions must not be delayed. 1, 3
• Initiate post-exposure prophylaxis as soon as possible after exposure, ideally within 24 hours, but treatment should be started immediately upon recognition of exposure even if weeks, months, or over a year have elapsed. 2, 4, 3
• There is no absolute cutoff for initiating post-exposure prophylaxis—rabies incubation periods can exceed 1 year in humans, making delayed treatment still potentially life-saving. 2, 4, 3
• When administered promptly and appropriately, the complete regimen (HRIG plus vaccine series) is nearly 100% effective in preventing human rabies. 1, 2, 4, 5
• No failures of post-exposure prophylaxis have been documented in the United States since current cell culture biologics have been licensed when the protocol is properly followed. 1, 2

Schedule Flexibility and Deviations

• Small delays of a few days for individual vaccine doses are unimportant and do not compromise protection. 2, 4
• If a patient misses the scheduled day 3 dose and presents later (e.g., day 5), give the second dose on that day without restarting the series. 4
• For substantial deviations (weeks or more), immune status should be assessed by serologic testing 7-14 days after the final dose. 2
• Most interruptions do not require restarting the entire series. 2

Pregnancy

• If substantial risk of rabies exposure exists, pre-exposure or post-exposure prophylaxis may be indicated during pregnancy. 1

Common Pitfalls to Avoid

• Do not delay post-exposure prophylaxis while waiting for animal testing results—initiate treatment immediately and discontinue only if laboratory testing confirms the animal is not rabid. 2, 3
• Do not withhold treatment based on the interval since exposure—even years-old exposures warrant treatment if clinical rabies has not developed. 2, 3
• Do not administer HRIG after day 7—it may interfere with the active immune response already generated by the vaccine. 2, 4, 3
• Do not give HRIG to previously vaccinated immunocompetent persons—it is unnecessary and will inhibit the anamnestic response. 2, 4, 3
• Do not use the gluteal area for vaccine administration—this is associated with inadequate immune response and vaccine failure. 1, 2, 3
• Do not exceed 20 IU/kg of HRIG—higher doses suppress active antibody production. 1, 2, 4
• For immunocompromised patients, do not use the standard 4-dose schedule—upgrade to the 5-dose regimen. 2, 4

Adverse Events

• Mild systemic reactions (fever, headache, dizziness, gastrointestinal symptoms) occur in 6.8-55.6% of vaccine recipients and are more frequent than serious adverse events. 2
• Local injection-site reactions (pain, redness, swelling) are reported in 60-89.5% of recipients and typically resolve spontaneously within a few days. 2
• Adverse reactions to HRIG are rare, occurring in approximately 0.183-11.4% of patients, and are typically mild and transient (local pain, erythema, itching, headache, body ache, fever, malaise). 2, 6, 7
• Immediate hypersensitivity reactions (anaphylaxis) are extremely rare (~1 in 10,000 vaccinees). 2
• Do not discontinue the vaccine series for mild systemic reactions such as fever—continuation is essential for protection against a uniformly fatal disease. 2
• Treat fever with age-appropriate dosing of acetaminophen (10-15 mg/kg every 4-6 hours) or ibuprofen (5-10 mg/kg every 6-8 hours). 2