Overview
Rabies
1. Clinical Overview
Summary
Rabies is a viral encephalitis caused by Lyssaviruses (most commonly Rabies virus – RABV), transmitted through the saliva of infected animals, primarily via bites, scratches, or licks to mucous membranes/broken skin. Once clinical symptoms develop, rabies is virtually 100% fatal. There is no effective treatment for established disease. However, rabies is almost 100% preventable with appropriate Post-Exposure Prophylaxis (PEP), which must be started as soon as possible after exposure. Wound cleaning, rabies vaccine, and Rabies Immunoglobulin (RIG) are the cornerstones of PEP. Dogs are responsible for >99% of human rabies deaths worldwide, though bats are the main reservoir in the Americas and Europe. Rabies kills approximately 59,000 people per year globally, predominantly in Africa and Asia. [1,2]
Clinical Pearls
"100% Fatal, 100% Preventable": Once neurological symptoms appear, there is no cure. But PEP before symptoms is highly effective.
Hydrophobia is Pathognomonic: Spasm of pharyngeal and respiratory muscles on attempting to swallow water. Classic but late sign.
Dogs Cause 99% of Human Deaths: Mass dog vaccination is the key to eliminating human rabies in endemic countries.
All Bat Bites/Scratches = PEP: Even if bite is not felt. Bats can have very small bite marks.
2. Epidemiology
Global Burden
- Deaths: ~59,000 per year worldwide. Underreported.
- Geographic: Endemic in Africa, Asia (especially India). Eliminated from Western Europe, Australia, most of the Americas (except bat rabies).
- Reservoirs: Dogs (Global), Bats (Americas, Europe), Foxes, Raccoons, Mongooses.
At-Risk Groups
| Group | Risk |
|---|---|
| Travellers to endemic areas | Dog bites, particularly children. |
| Children | More likely to be bitten, less likely to report. Higher mortality. |
| Rural populations (Asia, Africa) | Close contact with dogs, limited PEP access. |
| Veterinarians, animal handlers | Occupational exposure. |
| Caving/Potholing enthusiasts | Bat exposure. |
3. Pathophysiology
Mechanism
- Inoculation: Virus enters through bite wound (saliva). Can also enter via scratches, licks on broken skin/mucosa.
- Local Replication: Virus replicates in muscle tissue at the wound site (can last weeks to months – "incubation period").
- Neurotropism: Virus binds to nicotinic acetylcholine receptors at neuromuscular junction.
- Retrograde Axonal Transport: Virus travels along peripheral nerves towards the CNS at ~50-100mm/day.
- CNS Infection: Virus reaches and replicates in the spinal cord and brain (brainstem, limbic system heavily affected).
- Clinical Disease: Encephalitis (Furious) or Myelitis (Paralytic). Brainstem involvement causes hydrophobia, aerophobia, autonomic dysfunction.
- Centrifugal Spread: Virus spreads from CNS back to peripheral organs (salivary glands – shedding in saliva).
- Death: Cardiorespiratory failure.
Incubation Period
- Range: 1 week to >1 year. Average 1-3 months.
- Shorter if: Bites to head/face/hands (shorter distance to CNS), deep bites, high viral load.
4. Differential Diagnosis
| Condition | Key Features |
|---|---|
| Rabies Encephalitis | Animal bite history. Endemic area. Hydrophobia, Aerophobia (pathognomonic). Agitation. |
| Other Viral Encephalitis (HSV, JE) | May lack hydrophobia. CSF findings. PCR positive. |
| Tetanus | Wound history. Trismus (lockjaw). Opisthotonus. No hydrophobia. No encephalopathy. |
| Guillain-Barré Syndrome | Ascending flaccid paralysis. Albumino-cytological dissociation in CSF. No encephalopathy. |
| Delirium Tremens | Alcohol withdrawal history. Tremor, Confusion, Hallucinations. |
| Psychogenic/Conversion Disorder | Rare misdiagnosis. Must exclude organic cause. |
5. Clinical Presentation
Phases of Rabies
1. Prodrome (2-10 Days)
2. Acute Neurological Phase (2-7 Days)
Furious Rabies (80%)
| Feature | Notes |
|---|---|
| Hydrophobia | Spasm of pharyngeal muscles on attempting to swallow. Patient terrified of water. |
| Aerophobia | Spasm triggered by air on face. |
| Agitation, Hyperactivity | Periods of confusion and lucidity. |
| Autonomic Instability | Hypersalivation (Foaming), Lacrimation, Piloerection, Fluctuating BP/HR. |
| Hypersexuality | Rare. |
| Seizures | Can occur. |
Paralytic Rabies (20%)
3. Coma and Death (Days to Weeks)
Non-specific
Fever, Malaise, Headache.
Paraesthesia/Pain at Bite Site
Tingling, Itching, Burning. Highly suggestive if present after animal bite.
6. Investigations
Pre-Mortem Diagnosis (Difficult)
| Test | Sample | Notes |
|---|---|---|
| Rabies RT-PCR | Saliva, CSF, Skin biopsy (nuchal – hair follicle nerves) | Most specific. May be negative early. |
| Direct Fluorescent Antibody (DFA) | Skin biopsy (nuchal) | Detects viral antigen. |
| Serology (Antibodies) | Serum, CSF | Only useful in unvaccinated – presence of antibodies confirms exposure/infection. Vaccinated patients will have antibodies anyway. |
| CSF | LP | May show mild pleocytosis, elevated protein. Often normal. |
| MRI Brain | Imaging | Non-specific. May show brainstem/basal ganglia changes. |
Post-Mortem Diagnosis
- DFA on Brain Tissue: Gold Standard for confirmation. Negri bodies (inclusion bodies) in neurons.
Animal Investigation
- If animal available: Capture and observe for 10 days (dogs/cats). If develops signs = rabid. Post-mortem DFA on brain if animal dies.
7. Management
Management Algorithm
ANIMAL BITE / SCRATCH / LICK
(Especially Dog, Bat, or Wild Animal in Endemic Area)
↓
IMMEDIATE WOUND CARE (CRITICAL)
- Wash wound with copious SOAP + WATER for 15+ minutes
- Apply Povidone-Iodine OR Alcohol
- DO NOT SUTURE (Unless essential for haemostasis)
↓
ASSESS EXPOSURE CATEGORY (WHO)
┌─────────────────────────────────────────────────────────────┐
│ Cat I: Touch/Feed, Lick on intact skin → No PEP│
│ Cat II: Nibble, Minor scratch (no bleeding) → Vaccine│
│ Cat III: Bite/Scratch with bleeding, Lick on broken │ │
│ skin/mucosa, Bat exposure →Vaccine │
│ + RIG │
└─────────────────────────────────────────────────────────────┘
↓
POST-EXPOSURE PROPHYLAXIS (PEP)
┌──────────────────────────────────────┐
│ CATEGORY II & III: │
│ RABIES VACCINE │
│ - IM (Deltoid): Days 0, 3, 7, 14 │
│ (Some regimens: Day 0, 3, 7, 21) │
│ - Intradermal (2-site): Days 0, 3, │
│ 7, 28 (where approved) │
│ │
│ CATEGORY III ONLY: │
│ + RABIES IMMUNOGLOBULIN (RIG) │
│ - Human RIG (HRIG) 20 IU/kg │
│ - Infiltrate into AND around wound │
│ - Remainder IM at distant site │
│ - ONLY on Day 0 (or up to Day 7) │
└──────────────────────────────────────┘
↓
TETANUS PROPHYLAXIS
(As per wound guidelines)
↓
ANTIBIOTICS (If wound infected)
↓
IF SYMPTOMS DEVELOP:
- Confirm diagnosis (RT-PCR, DFA)
- Palliative Care (No proven treatment)
- Intensive Care (Limited benefit)
- "Milwaukee Protocol" (Induced coma + antivirals
– Minimal success, largely abandoned)
Wound Care (Most Important First Step)
- Mechanical cleaning removes virus.
- Wash with soap and water for at least 15 minutes.
- Apply virucidal agent: Povidone-Iodine (Betadine) or 70% Ethanol.
- Avoid wound closure if possible (increases infection risk).
Rabies Vaccine (Cell-Culture Based)
| Regimen | Schedule | Notes |
|---|---|---|
| Essen (IM, 5-dose) | Days 0, 3, 7, 14, 28 | WHO standard. Sometimes given as 4 doses. |
| Zagreb (IM, 2-1-1) | Days 0 (2 doses L+R Deltoid), 7, 21 | Fewer visits. |
| Intradermal (2-site) | Days 0, 3, 7, 28 | Cost-effective. Requires trained staff. |
- Previously vaccinated individuals: 2 booster doses (Day 0, 3). No RIG needed.
Rabies Immunoglobulin (RIG)
- Provides immediate passive immunity while vaccine response develops.
- Indication: Category III exposures only.
- HRIG (Human): 20 IU/kg. Preferred.
- ERIG (Equine): 40 IU/kg. Risk of serum sickness. Used where HRIG unavailable.
- Administration: Infiltrate as much as possible into and around the wound. Remainder given IM at a site distant from vaccine.
- Timing: Day 0 only (up to Day 7). Do not give after Day 7 (vaccine immunity developing).
Pre-Exposure Prophylaxis (PrEP)
- For high-risk groups: Veterinarians, Animal handlers, Laboratory workers, Travellers to endemic areas.
- Schedule: 3 doses IM or ID (Day 0, 7, 21-28). Booster as needed based on antibody titres.
8. Established Rabies (No Cure)
- Once symptoms appear, rabies is virtually 100% fatal.
- Supportive/Palliative Care: Sedation for comfort, Hydration, Nutrition.
- "Milwaukee Protocol": Induced coma + Ketamine + Ribavirin + Amantadine. less than 20 survivors reported worldwide (many had bat rabies variant or initiated immunity). Not recommended routinely.
9. Complications
| Complication | Notes |
|---|---|
| Death | Inevitable once symptomatic (>99.99%). |
| Cardiorespiratory Failure | Immediate cause of death. |
| Severe Autonomic Dysfunction | Arrhythmias, Hypersalivation, Hyperthermia. |
| Secondary Infections | Aspiration Pneumonia. |
10. Prognosis and Outcomes
- Untreated Exposure: If no PEP given, mortality varies by bite location (Head/Face = higher risk).
- PEP Given Correctly: ~100% survival.
- Symptomatic Rabies: Virtually 100% fatal.
11. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Rabies Post-Exposure Prophylaxis | WHO (2018) | Wound washing, Vaccine schedules, RIG for Category III. |
| PHE Rabies Guidance | UK PHE (UKHSA) | PEP for travellers, Risk assessment algorithm. |
12. Patient and Layperson Explanation
What is Rabies?
Rabies is a deadly virus spread through the saliva of infected animals, usually by a bite. It attacks the brain and is almost always fatal once symptoms appear. However, it is almost completely preventable if treated immediately after a bite.
What should I do if I'm bitten?
- Wash the wound immediately with soap and running water for at least 15 minutes.
- Apply antiseptic (like Betadine or alcohol) if available.
- See a doctor urgently for Post-Exposure Prophylaxis (PEP) – a series of vaccinations, and possibly an injection around the wound.
Is there a cure?
There is no cure once symptoms develop. But the vaccine and immunoglobulin given after a bite (before symptoms) are highly effective at preventing the disease.
Who is at risk?
Anyone bitten by a dog, bat, or wild animal in a country where rabies is common. Travellers to Africa, Asia, and parts of South America should consider pre-exposure vaccination.
13. References
Primary Sources
- WHO. Rabies vaccines: WHO position paper. Wkly Epidemiol Rec. 2018;93:201-220.
- Hemachudha T, et al. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol. 2002;1(2):101-9. PMID: 12849514.
14. Examination Focus
Common Exam Questions
- Pathognomonic Sign: "What is the classic sign of Rabies Encephalitis?"
- Answer: Hydrophobia (Spasm on attempting to swallow water). Also Aerophobia.
- PEP Components: "What are the components of Post-Exposure Prophylaxis for Category III exposure?"
- Answer: Wound Washing + Rabies Vaccine + Rabies Immunoglobulin (RIG, infiltrated into wound).
- RIG Timing: "When should Rabies Immunoglobulin be given?"
- Answer: Day 0 only (or up to Day 7 if not given earlier). Do not give after Day 7.
- Prognosis: "What is the mortality of symptomatic rabies?"
- Answer: Virtually 100% fatal.
Viva Points
- Category III Exposure: Define it (Bite with bleeding, Lick on broken skin/mucosa, Bat exposure).
- Wound Care: Emphasise 15 minutes of soap and water as the most important first step.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.