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Infectious Diseases›Condition·Updated Apr 17, 2026·v1

Rabies

Rabies is a fatal viral encephalitis transmitted via animal saliva. Prevention through immediate wound care and post-exposure prophylaxis (vaccine + immunoglobulin) is the only effective management strategy.

High Evidence270 references·1,159 words·5 min read·v1
rabieslyssaviruszoonosisencephalitispost-exposure prophylaxisinfectious diseases

Quick Reference

RxDrug of choiceRabies Vaccine (cell-culture derived) + Human Rabies Immunoglobulin (HRIG)
AltAlternativesRabies Monoclonal Antibodies (e.g., Zamerovimab, Mazorelvimab)
⊘AvoidDo not withhold PEP for any reason (including pregnancy) following a high-risk exposure; avoid the Milwaukee Protocol.
DxTest of choiceRT-PCR of saliva or nuchal skin biopsy (antemortem); DFA of brain tissue (postmortem)
ScKey scoreWHO Rabies Exposure Categories (I, II, III)
→When to referRefer for any Category III exposure requiring RIG; refer all symptomatic cases for ICU/palliative care.
Rabies is 100% fatal once symptoms start but 100% preventable with immediate wound washing, vaccination, and immunoglobulin infiltration.
Rabies is an acute, progressive, and nearly 100% fatal zoonotic viral encephalitis caused by neurotropic RNA viruses of the genus Lyssavirus. While the disease is entirely preventable through timely post-exposure prophylaxis (PEP), it continues to cause approximately 59,000 deaths annually, primarily in Asia and Africa. Transmission occurs when infected saliva is inoculated into tissues via bites or scratches from animal reservoirs, most commonly domestic dogs and bats.

Overview and Recommendations

Background

  • •Recognize rabies as a fatal caused by the rabies virus (RABV) and other lyssaviruses, which are bullet-shaped, single-stranded RNA viruses that are exquisitely neurotropic.
  • •Identify the primary global reservoir as the domestic dog, responsible for 99% of human deaths, while recognizing that in the Americas, bats are the most frequent source of human infection.
  • •Understand the unique pathophysiology involving retrograde axonal transport, where the virus travels from the site of inoculation to the spinal cord and brain at a rate of approximately 12–100 mm per day.
  • •Differentiate between the two clinical phenotypes: the encephalitic (furious) form, characterized by agitation and hydrophobia (80% of cases), and the paralytic (dumb) form, characterized by ascending weakness (20% of cases).
  • •Note the highly variable incubation period, which typically lasts 20 to 90 days but can range from less than one week to over one year depending on the viral load and the proximity of the bite to the central nervous system.
  • •Acknowledge the "Zero by 30" global initiative, which aims to eliminate dog-mediated human rabies deaths by 2030 through mass dog vaccination and improved access to human biologics.

Evaluation

  • •Suspect rabies in any patient presenting with acute, progressive neurological symptoms, especially if they have a history of animal contact or have recently traveled to an endemic region.
  • •Ask specifically about the "bite history," including minor scratches or licks on broken skin, and note that patients may not recall an exposure, particularly with bats, which have small teeth that leave minimal marks.
  • •Look for the pathognomonic early sign of localized paresthesia, pain, or intense pruritus at the site of the original (and often healed) exposure, which occurs in about 50% of patients.
  • •Perform a "water test" to provoke hydrophobia: offer the patient a glass of water and observe for violent, involuntary spasms of the diaphragm and pharyngeal muscles triggered by the attempt to drink.
  • •Assess for aerophobia by fanning a draft of air across the patient's face, which may trigger similar spasmodic gasping or psychomotor agitation.
  • •Evaluate for autonomic instability, including "autonomic storms" characterized by hypersalivation (foaming at the mouth), profuse sweating, and fluctuating blood pressure or heart rate.
  • •Distinguish paralytic rabies from by noting the presence of fever, early bladder dysfunction, and the relentless progression to coma in rabies, whereas GBS often lacks these features.
  • •Order antemortem diagnostic testing including RT-PCR of saliva (collect three samples 3–6 hours apart) and a full-thickness nuchal skin biopsy (3–5 mm) from the posterior hairline to detect viral antigen in cutaneous nerves.
  • •Obtain serum and cerebrospinal fluid (CSF) for rabies virus neutralizing antibodies (RVNA); the presence of antibodies in the CSF is highly specific for rabies encephalitis in both vaccinated and unvaccinated individuals.
  • •Utilize Magnetic Resonance Imaging (MRI) to rule out other causes of encephalitis; while often normal early on, rabies may eventually show T2-hyperintensities in the brainstem, hippocampus, and gray matter.
  • •Rule out other differential diagnoses such as Japanese encephalitis, , cerebral malaria, and acute drug toxicity (e.g., poisoning).

Management

  • •Categorize the exposure immediately: Category I (touching/licking intact skin) requires no treatment; Category II (minor scratches without bleeding) requires immediate vaccination; Category III (transdermal bites/scratches or bat contact) requires vaccination plus immunoglobulin.
  • •Wash all wounds immediately and thoroughly with soap and water or povidone-iodine for at least 15 minutes; this mechanical action is the most critical step in reducing viral load.
  • •Administer Human Rabies Immunoglobulin (HRIG) at a dose of 20 IU/kg (or Rabies Monoclonal Antibodies at 0.3 mg/kg) for all Category III exposures in previously unvaccinated individuals.
  • •Infiltrate the entire dose of HRIG into and around the wound site; if the volume is insufficient for multiple wounds, dilute it in sterile saline to ensure adequate coverage of all injury sites.
  • •Initiate the rabies vaccine series (Essen regimen) with intramuscular injections (0.5 or 1.0 mL depending on product) on days 0, 3, 7, and 14 for immunocompetent patients.
  • •Add a fifth vaccine dose on day 28 for immunocompromised patients and monitor serology to ensure the RVNA titer reaches the protective threshold of ≥ 0.5 IU/mL.
  • •Provide a 2-dose booster series (days 0 and 3) for previously vaccinated individuals who experience a new exposure; these patients do NOT require rabies immunoglobulin.
  • •Administer antibiotic prophylaxis (e.g., Amoxicillin-clavulanate 875/125 mg twice daily for 3–5 days) for high-risk animal bites to prevent secondary bacterial infection from oral flora like Pasteurella.
  • •Admit symptomatic patients to a quiet, low-stimulus isolation room to prevent triggering painful spasms and to protect healthcare workers from contact with infectious saliva.
  • •Manage agitation and spasms with heavy sedation using benzodiazepines (e.g., Diazepam 5–10 mg IV every 4–6 hours) or antipsychotics (e.g., Haloperidol).
  • •Avoid the "Milwaukee Protocol" (therapeutic coma), as multiple clinical trials have shown it is ineffective and does not improve survival.
  • •Provide aggressive palliative care, including IV fluids for hydration and opioids for pain, ensuring a dignified end-of-life process for the patient and support for the family.
  • •Notify public health authorities immediately of any suspected human or animal rabies case to facilitate contact tracing and environmental control measures.
  • •Refer all symptomatic cases to a tertiary care center with intensive care capabilities, though the prognosis remains near-universally fatal regardless of the level of care.

Board Review — High Yield

  • •Negri bodies — Eosinophilic cytoplasmic inclusions in neurons (hippocampus/cerebellum) pathognomonic for rabies.
  • •Retrograde axonal transport — The mechanism by which the virus travels from the periphery to the CNS via dynein motors.
  • •Nicotinic acetylcholine receptor — The primary receptor at the neuromuscular junction used by the rabies virus for entry.
  • •Hydrophobia — Involuntary pharyngeal spasms triggered by the sight or sound of water; classic sign of encephalitic rabies.
  • •Bat exposure — PEP is indicated even if a bite is not felt if a person was in a room with a bat and cannot rule out contact (e.g., sleeping, intoxicated).
  • •Category III Exposure — Requires both vaccine and RIG; RIG must be infiltrated into the wound.
  • •Incubation period — Highly variable (days to years), but typically 1–3 months.
  • •Vaccine type — Modern rabies vaccines are inactivated (killed) virus grown in cell cultures (e.g., Vero cells).

Deep Dive — Evidence Details

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