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Rabies Post-Exposure Prophylaxis

Post-Exposure / Viral

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1. Clinical Syndrome

Prevention of clinical rabies via active (vaccine) + passive (rabies immune globulin, HRIG) immunization after potential exposure to a rabid animal. Rabies is essentially 100% fatal once symptomatic — PEP must be given before symptoms develop.

Excludes: symptomatic rabies (Milwaukee Protocol is investigational; no reliable cure), pre-exposure vaccination (for high-risk occupations + travelers — different schedule).

2. Pathogens

Consider the exposure: Animal species (bat exposure even questionable = treat; wild carnivore bite = treat; domestic dog/cat in non-endemic + observable = wait), location (rabies-endemic vs free), wound severity (Category I no contact / II superficial scratch / III bite or mucous membrane exposure), bat in same room during sleep (treat per CDC + WHO).

Consider the patient: Prior rabies vaccination status, immunocompromise (may need extra vaccine dose), pregnancy (no contraindication — PEP must be given), local availability of vaccine + HRIG.

Common

    • Rabies Virus

      Lyssavirus, Rhabdoviridae. Bat-borne in US; dog-borne globally.

3. Empiric Therapy

TierFirst choiceAlternativesDurationComments
Outpatient
  • Rabies vaccine 1 mL IM (deltoid; anterior thigh in infants) · Days 0, 3, 7, 14 (4-dose series; add day 28 dose if immunocompromised) · IM
  • Human Rabies Immune Globulin (HRIG) 20 IU/kg · × 1 dose on day 0 (or as soon as possible — up to day 7 of vaccine series acceptable) · infiltrate around wound + remainder IM at distant site (away from vaccine site)
  • Equine RIG (ERIG) 40 IU/kg · × 1 · infiltrate + IM

    Used when HRIG unavailable; check skin sensitivity first.

  • Rabies monoclonal antibody (rabivig / monobyt) — · — · Per local availability

    WHO-prequalified options replacing HRIG in some regions.

Single 4-dose vaccine series + single HRIG. Add 5th vaccine dose day 28 in immunocompromised.**Start within hours of exposure.** **Wound care first**: copious soap + water irrigation × 15 min, povidone-iodine if available, no suturing if avoidable. **HRIG infiltration around wound** is critical — vaccine alone is not enough for high-exposure cases.
Outpatient — with comorbidities
  • Rabies vaccine (2-dose abbreviated for previously vaccinated) 1 mL IM · Days 0 + 3 only · IM
—2 doses only — no HRIG needed for previously vaccinated**Previously vaccinated (pre-exposure or PEP)** with documented antibody response — abbreviated 2-dose series on days 0 + 3. **NO HRIG** needed. Verify previous vaccination + titer if uncertain.

4. Directed Therapy

Exposure assessment drives decision:

Animal-specific:

  • Bat exposure: ANY direct contact + suspected (e.g., bat in room during sleep, person can't reliably exclude contact) → PEP. Bat in closed building during sleep + unable to confirm no exposure → PEP.
  • Wild carnivore (raccoon, skunk, fox, coyote, bobcat, mongoose): bite or scratch → assume rabid + PEP (animal testing prevents PEP only if available + negative).
  • Domestic dog / cat / ferret in rabies-endemic region (most US): observe healthy animal × 10 days; if becomes ill or dies, test + start PEP retroactively. If unobservable / wild / unknown → PEP.
  • Domestic dog / cat in rabies-free region: minimal risk; assess local epidemiology.
  • Small rodents / lagomorphs (squirrels, rats, mice, hamsters, rabbits): virtually never rabid in US; PEP not indicated.
  • Large rodents (groundhogs, woodchucks): very rare positives; consult public health.
  • Livestock + horses: depends on local epidemiology; usually PEP given.

Wound care first:

  • Copious soap + water irrigation × 15 min
  • Povidone-iodine if available
  • Avoid primary closure if possible (or delay with antibiotic prophylaxis)
  • Tetanus prophylaxis update
  • Consider bacterial infection prophylaxis (amox-clav for animal bite)

PEP regimen (previously unvaccinated):

  • Vaccine: 1 mL IM days 0, 3, 7, 14 (deltoid adults, anterior thigh infants; NOT gluteal — poor response)
  • HRIG: 20 IU/kg total — infiltrate as much as possible around wound, remainder IM at distant site (NEVER mix with vaccine syringe / site)
  • Immunocompromised: add 5th dose day 28; check titer post-completion

Previously vaccinated (pre-exposure or completed PEP):

  • Vaccine: 2 doses days 0 + 3
  • NO HRIG

Adjuncts: rabies vaccine confers anti-rabies AND tetanus boost effect modest only; ensure tetanus separately. Antibiotic prophylaxis for bite wounds (amox-clav 875 mg BID × 3–5 days for dog / cat / human bites).

5. Monitoring

Resolution: wound healing, no symptom development (incubation 1–3 months typically; can be days to year+). Symptom onset = uniformly fatal — PEP failure essentially never occurs with adherent guidelines-based regimens.

Post-PEP titer check in immunocompromised — adequate response if rapid fluorescent focus inhibition test (RFFIT) titer ≥0.5 IU/mL or VNA ≥1:5.

Toxicity: vaccine — injection site soreness, low-grade fever, headache (common, mild). HRIG — injection site pain, fever, rare anaphylaxis (less than equine product).

Pearls

ANY bat exposure = PEP, including bat in bedroom during sleep without confirmed direct contact (CDC/ACIP). Wash wound 15 min with soap + water FIRST — single biggest factor reducing rabies risk. HRIG must be infiltrated AROUND THE WOUND — IM-only HRIG without infiltration is much less effective. Previously vaccinated = 2 doses, NO HRIG. Immunocompromised = 5 doses + titer check. No contraindications — pregnancy is NOT a barrier. Animal observation × 10 days for domestic dog/cat in US — if healthy at end, no PEP needed; if dies or symptoms, test + start PEP. Pre-exposure prophylaxis for veterinarians, lab workers, travelers: 2-dose series (days 0, 7); if exposed later, 2 booster doses only (no HRIG).

References