Clinical Subject Page

Rabies

Rabies is a fatal viral infection of the central nervous system caused by the rabies virus. It is a zoonotic disease transmitted mainly through the saliva of infected mammals, most commonly through bites. Once clinical neurological symptoms develop, the disease is almost invariably fatal, but prompt post-exposure prophylaxis can prevent disease before symptoms begin

Also called

Rabies virus infection

ICD-10

A82.9

Specialty

Infectious

Onset

Acute

Reviewed

August 2026

On This Page

Overview

Overview
Etiology & Risk Factors

Etiology & Risk Factors
Pathophysiology

Pathophysiology
Clinical Presentation

Clinical Presentation
History Taking

History Taking
Physical Examination

Physical Examination
Investigations

Investigations
Diagnosis

Diagnosis
Management

Management
Complications

Complications
Prognosis

Prognosis
Key Points / Clinical Pearls

Key Points / Clinical Pearls

Overview

–Rabies primarily affects the brain and spinal cord after the virus travels from the site of inoculation through peripheral nerves toward the central nervous system.

Human infection is usually caused by bites or scratches from infected mammals. Dogs are responsible for the vast majority of human cases globally.

-The disease has two major clinical patterns:

Furious rabies: agitation, hydrophobia, hallucinations, and autonomic instability.
Paralytic rabies: progressive flaccid paralysis resembling Guillain-Barré syndrome.

Teaching point Once clinical Rabies symptoms appear, treatment is mainly supportive and survival is exceptionally rare; therefore, prevention through prompt post-exposure prophylaxis is critical.

Etiology & Risk Factors

-Etiology

–Rabies is caused by rabies virus, an enveloped, single-stranded RNA virus of the Rhabdoviridae family.

The virus is introduced into tissue through infected saliva and initially replicates locally before entering peripheral nerves.

-Risk Factors

Bite or scratch from a potentially infected mammal
Exposure to unvaccinated dogs in endemic areas
Contact with bats
Occupational animal exposure
Living in or traveling to rabies-endemic regions

Pathophysiology

Animal bite or scratch → viral inoculation into tissue → local viral replication → entry into peripheral nerves → retrograde axonal transport → central nervous system infection → encephalitis → autonomic and neurological dysfunction → coma and death

Clinical Presentation

-Symptoms:

Early symptoms include:

Fever
Headache
Weakness
Malaise
Pain, tingling, or itching at the bite site

Later symptoms may include:

Anxiety
Agitation
Confusion
Hallucinations
Difficulty swallowing
Hydrophobia
Aerophobia
Excessive salivation

-Signs:

Fever
Agitation or altered mental status
Pharyngeal spasms
Hypersalivation
Autonomic instability
Progressive neurological dysfunction
Encephalitis
Generalized spasms
Paralysis
Respiratory failure

Important Note Hydrophobia is highly characteristic of clinical Rabies but is not present in every patient, particularly those with the paralytic form.

History Taking

-Ask about:

Animal bite or scratch
Species and behavior of the animal
Date and location of exposure
Whether saliva contacted broken skin or mucosa
Whether the animal was available for observation or testing
Previous rabies vaccination
Previous post-exposure prophylaxis
Travel or residence in an endemic area
Onset of fever or neurological symptoms

Physical Examination

-General Examination

Temperature
Mental status
Hydration
Cardiovascular and respiratory status
Signs of autonomic dysfunction

-System-Specific Examination:

Neurological examination
Assessment for pharyngeal spasms
Assessment for cranial nerve abnormalities
Assessment for progressive weakness or paralysis
Examination of the exposure wound

Investigations

-Biochemistry / Specific Tests

Testing is mainly required when clinical disease is suspected.

Serum and cerebrospinal fluid testing for rabies-specific antibodies
Molecular detection of viral RNA by Polymerase Chain Reaction (PCR) from appropriate specimens
Routine biochemical tests to assess organ dysfunction in severe disease

-Imaging

Not routinely required to diagnose Rabies.

Brain imaging may be used to exclude alternative neurological diagnoses.

-Special / Confirmatory Tests

Diagnosis of clinical Rabies requires specialized laboratory testing coordinated with public-health authorities. Testing may involve saliva, nuchal skin biopsy, cerebrospinal fluid, or serum depending on the clinical stage.

Important Investigation Note

Post-exposure prophylaxis should never be delayed while waiting for diagnostic testing when a significant exposure has occurred.

Diagnosis

-Clinical Rabies is suspected in a patient with:

Compatible animal exposure → prodromal symptoms → progressive encephalitis, hydrophobia, or paralysis.

-Laboratory diagnosis is performed using specialized PCR and antibody testing, but management of an exposure is based primarily on the exposure risk rather than waiting for laboratory confirmation.

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Management

Rabies · Post-Exposure Prophylaxis (PEP)

PEP — The Only Effective Intervention After Exposure

Step	Action	Critical rule
Step 1 Wound wash	Immediate and thorough washing with soap and water for 15 minutes minimum — most important single intervention. Then irrigate with povidone-iodine or 70% alcohol.	Do this BEFORE going to hospital. Reduces viral load at entry site. Never suture immediately — delay or avoid primary closure.
Step 2 Risk assess	Category I: touching/feeding animal, licks on intact skin → no PEP needed. Category II: nibbling, minor scratches without bleeding → vaccine only. Category III: transdermal bites, scratches with bleeding, licks on broken skin, mucous membrane exposure → vaccine + RIG.	WHO exposure categories I / II / III — determines PEP regimen
Step 3 Rabies immunoglobulin (RIG)	Human RIG (HRIG) 20 IU/kg — infiltrate as much as possible around wound; remainder IM at distant site. Equine RIG (ERIG) 40 IU/kg — if HRIG unavailable; skin test first. Give on day 0 only — never after day 7.	Category III only. Give with 1st vaccine dose — different site. Provides immediate passive immunity while vaccine response develops.
Step 4 Rabies vaccine	Previously unvaccinated: 4 doses — days 0, 3, 7, 14 (IM deltoid) Previously vaccinated: 2 doses only — days 0 + 3 (no RIG needed) Vaccine: cell-culture vaccine (HDCV, PCECV) — not nerve tissue vaccines	Never inject in gluteal — poor immune response. Deltoid only (thigh in infants). Start as soon as possible — no upper time limit if exposure confirmed.

PEP is nearly 100% effective if started promptly and completed. Once clinical symptoms appear — no treatment has reliably prevented death. RIG and vaccine MUST be given at different anatomical sites. Never mix in same syringe.

Pre-Exposure Prophylaxis (PrEP)

Who needs PrEP

Veterinarians, animal handlers, wildlife workers

Laboratory workers handling rabies virus

Travellers to endemic areas staying >1 month or with significant animal exposure risk

Cavers (bat exposure risk)

PrEP schedule

3 doses IM deltoid — days 0, 7, 21 (or 28)

Booster every 2–5 years — depending on risk

If exposed after PrEP: 2 doses PEP only (days 0 + 3) — no RIG needed

Does NOT eliminate need for PEP — simplifies it

Rabies · Management of Established Disease & Supportive Care

Supportive / Palliative Management — Once Symptomatic

Problem	Management	Notes
Agitation / spasms	Midazolam infusion — 1st line sedation Diazepam IV PRN for breakthrough spasms Ketamine — anaesthetic doses for refractory agitation	Dark, quiet room — minimise stimuli triggering spasms (same as tetanus)
Hydrophobia / aerophobia	Deep sedation during episodes. NG tube — if oral route impossible. IV fluids for hydration.	Never force oral fluids — precipitates fatal laryngospasm
Respiratory failure	Mechanical ventilation — intubation early if paralytic form or declining GCS. Tracheostomy for prolonged ventilation.	May prolong survival but does not alter outcome once symptomatic
Autonomic instability	Cardiac monitoring — arrhythmias common. Labetalol — sympathetic surges. Atropine — bradycardia/vagal episodes.	Leading cause of death in ICU-managed patients
Pain / comfort	Morphine infusion — analgesia + reduces sympathetic surges. Palliative intent in most cases.	Goal shifts to comfort when prognosis confirmed
Milwaukee protocol	Induced coma (ketamine/midazolam) + antiviral agents (ribavirin/amantadine) + supportive ICU care. Used in the only well-documented survivor (Jeanna Giese, 2004).	Largely abandoned — replicated in <5 survivors out of hundreds of attempts. Not standard of care.

Prognosis: Once clinical rabies develops — mortality is virtually 100%. Fewer than 15 human survivors documented worldwide. Management goal becomes supportive/palliative. Family counselling + ethics team involvement essential. Organ donation NOT possible (transmissible).

Exam Summary — Must-Know Rules

PEP rules

Wound wash × 15 min soap + water — most important first step

Category III → RIG + 4 vaccine doses (days 0, 3, 7, 14)

Previously vaccinated → 2 doses only, no RIG

RIG: infiltrate wound first, remainder IM — different site from vaccine

RIG only on day 0 — never after day 7 (blocks vaccine response)

Vaccine — deltoid only, never gluteal

Exam differentiators

Hydrophobia + aerophobia = rabies until proven otherwise

Paraesthesia at bite site in prodrome = pathognomonic

Dumb rabies = ascending paralysis (GBS mimic) — no hydrophobia

Negri bodies = hippocampal neurons (post-mortem)

Virus travels in nerves — blood tests negative during infection

Milwaukee protocol — famous but not standard of care

Complications

Encephalitis
Hydrophobia
Respiratory failure
Autonomic instability
Cardiac arrhythmias
Paralysis
Coma
Multiorgan dysfunction
Death

Prognosis

The prognosis of Rabies depends critically on whether post-exposure prophylaxis is given before symptoms develop. Properly administered prophylaxis is highly effective at preventing disease. Once clinical neurological symptoms appear, Rabies is almost invariably fatal, and treatment is primarily supportive.

Key Points / Clinical Pearls

Rabies is a fatal viral infection of the central nervous system.
It is caused by rabies virus.
Transmission occurs mainly through the saliva of infected mammals.
Dog bites account for most human cases globally.
The virus travels through peripheral nerves to the central nervous system.
Incubation is usually weeks to months.
Early symptoms are nonspecific and may include fever and headache.
Hydrophobia and painful pharyngeal spasms are characteristic features.
A paralytic form can present with progressive weakness and paralysis.
There is no reliable curative treatment once clinical disease develops.
Immediate wound washing for at least 15 minutes is essential after a potentially infectious exposure.
Post-exposure prophylaxis includes vaccine and, when indicated, rabies immunoglobulin.
Previously vaccinated patients require a different PEP regimen.

World Health Organization (WHO). Rabies .
Centers for Disease Control and Prevention (CDC). Rabies .
World Health Organization (WHO). WHO Expert Consultation on Rabies: Third Report . Technical Report Series 1012.
Hemachudha T, Laothamatas J, Rupprecht CE. Human Rabies: A Disease of Complex Neuropathogenetic Mechanisms and Diagnostic Challenges. Lancet Neurol. 2002;1(2):101-109. PubMed .
Fooks AR, Cliquet F, Finke S, et al. Rabies. Nat Rev Dis Primers. 2017;3:17091. PubMed .
Manning SE, Rupprecht CE, Fishbein D, et al. Human Rabies Prevention — United States, 2008: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57(RR-3):1-28. CDC .
National Library of Medicine (NIH). Rabies . StatPearls.