When should Human Rabies Immunoglobulin (HRIG) be administered to a patient exposed to rabies?

When to Give Human Rabies Immunoglobulin (HRIG)

HRIG should be administered to all previously unvaccinated persons with rabies exposure (both bite and non-bite exposures) as soon as possible, ideally at the same time as the first vaccine dose (day 0), but can still be given up to and including day 7 of the post-exposure prophylaxis series. 1, 2, 3

Patient Selection: Who Gets HRIG

Give HRIG to:

• All previously unvaccinated persons with category III exposures (any bite or scratch that breaks the skin, or mucous membrane contamination with saliva or potentially infectious material) 1, 4
• All previously unvaccinated persons with category II exposures when the animal is confirmed or suspected rabid 1
• Immunocompromised patients even if previously vaccinated, as they require the full 5-dose vaccine series plus HRIG 2, 3

Do NOT give HRIG to:

• Persons who have previously received complete pre-exposure or post-exposure rabies vaccination with a cell culture vaccine - these individuals receive vaccine only (2 doses on days 0 and 3) 1, 2, 3
• Persons with documented adequate rabies antibody titers from prior vaccination 1, 4

Critical pitfall: Never give HRIG to previously vaccinated persons, as it will suppress the anamnestic antibody response that should occur rapidly after booster vaccination 3, 5

Timing of Administration

Optimal Window:

• Day 0 (simultaneously with first vaccine dose) is ideal for HRIG administration 1, 2, 3
• Up to and including day 7 after the first vaccine dose if not given initially 1, 2, 4
• Beyond day 7: Do NOT give HRIG - an antibody response to the vaccine is presumed to have occurred by this time, making passive immunization unnecessary and potentially suppressive 1, 2

Rationale for the 7-Day Cutoff:

The body begins producing its own vaccine-induced antibodies by day 7-10, making passive antibody administration both unnecessary and potentially counterproductive, as HRIG can partially suppress active antibody production 1, 5

Dosing

• Exactly 20 IU/kg body weight for all age groups, including children 1, 2, 3
• Never exceed the recommended dose - higher doses can suppress active antibody production 1, 2, 3
• A 2020 study demonstrated 98% adherence to proper dosing (within 10% of 20 IU/kg) in clinical practice 6

Anatomical Administration Technique

Wound Infiltration (Most Critical):

• Infiltrate the full calculated dose thoroughly in the area around and into all wounds if anatomically feasible 1, 2, 3
• This recommendation is based on reports of rare post-exposure prophylaxis failures when inadequate HRIG was infiltrated at exposure sites 1, 2
• Any remaining volume after wound infiltration should be injected intramuscularly at a site distant from vaccine administration 1, 2

Critical Administration Rules:

• Never administer HRIG in the same syringe or same anatomical site as the first vaccine dose - this may interfere with vaccine immunogenicity 1, 2, 3
• Subsequent vaccine doses in the series can be given in the same anatomic location where HRIG was administered 1

Major practice gap identified: A 2020 study found only 56% of eligible patients received proper wound infiltration with HRIG, despite this being a critical guideline recommendation 6

Type of Exposure Requiring HRIG

Definite Indications:

• Any penetration of skin by teeth (bite) - regardless of location, though face and hand bites carry highest risk 4
• Bat exposures with any physical contact when bite or mucous membrane contact cannot be excluded, as bat bites may be undetectable 4
• Non-bite exposures: scratches, abrasions, open wounds, or mucous membranes contaminated with saliva or potentially infectious material (e.g., brain tissue) from a rabid or suspected rabid animal 4

NOT Indications:

• Casual contact (petting a rabid animal) 4
• Contact with blood, urine, or feces of a rabid animal 4
• Exposure to dried material containing virus (virus is noninfectious when dry) 4

Vaccine Regimen Accompanying HRIG

• 4-dose vaccine schedule (days 0,3,7,14) for immunocompetent previously unvaccinated persons receiving HRIG 2, 3
• 5-dose vaccine schedule (days 0,3,7,14,28) for immunocompromised patients 2, 3
• Vaccine should be administered intramuscularly in the deltoid for adults or anterolateral thigh for children 1

Critical pitfall: Never use the gluteal area for vaccine injection - this produces inadequate antibody titers and has been associated with vaccine failure 3

Safety Profile

HRIG is remarkably safe with adverse events occurring in only 0.18-11.4% of recipients, consisting primarily of mild local reactions (pain, erythema, itching) and minor systemic symptoms (headache, fever, malaise) that resolve without complications 7, 8

Clinical Efficacy

When administered properly with vaccine, HRIG provides immediate passive immunity during the critical first 7 days before vaccine-induced antibodies develop, and has demonstrated 100% clinical efficacy in preventing rabies when given according to guidelines 7