Overview
Rabies
Topic Overview
Summary
Rabies is a near-universally fatal viral encephalitis caused by Lyssaviruses, transmitted through bites or scratches from infected mammals. Once clinical symptoms develop, rabies is almost invariably fatal. Post-exposure prophylaxis (PEP) with immediate wound care, rabies vaccine, and immunoglobulin is life-saving if given promptly after exposure. Pre-exposure vaccination is recommended for high-risk groups.
Key Facts
- Transmission: Bite/scratch from infected mammal; rarely through mucous membrane exposure or aerosol (bat caves)
- High-risk animals: Dogs (most common worldwide), bats, foxes, raccoons, wolves, jackals
- Incubation: 1-3 months (range: days to years) — shorter with bites to face/neck
- Once symptomatic: Almost 100% fatal (only ~15 documented survivors)
- PEP: Wound washing + rabies vaccine ± rabies immunoglobulin (RIG)
- UK is rabies-free: But bats carry European Bat Lyssaviruses (EBLV)
Clinical Pearls
Time is critical — PEP must start immediately post-exposure; there is no upper time limit for starting PEP after exposure
Any bat contact where bite cannot be excluded = PEP indicated (bat bites can be very small and go unnoticed)
Rabies is "the bite that kills" — always take animal bites in endemic areas seriously
Why This Matters Clinically
Rabies is 100% preventable with timely PEP but 100% fatal once symptomatic. Clinicians must recognise high-risk exposures, understand PEP indications, and know how to access vaccines and immunoglobulin. In the UK, specialist advice is available 24/7 from Public Health England.
Visual Summary
Visual assets to be added:
- World rabies endemic country map
- Post-exposure prophylaxis algorithm
- Wound care steps infographic
- Negri body histopathology image
Epidemiology
Global Burden
- Deaths: ~59,000/year globally (99% in Asia and Africa)
- Most deaths: India (35%), followed by Africa
- Dog bites: Account for 99% of human rabies deaths
- Children: 40% of deaths in children under 15
Geographic Distribution
- Endemic: Africa, Asia (especially India, Bangladesh, Pakistan), South America
- Rabies-free: UK, Ireland, Australia, New Zealand, Japan, Western Europe (mainland mostly eliminated)
- Bat rabies: Present even in "rabies-free" countries (European Bat Lyssavirus in UK bats)
UK Situation
- Last indigenous human rabies: 1902
- Imported cases: ~1 every few years (last: 2018, Morocco dog bite)
- EBLV in UK bats: Rare but present; one human death (2002, bat handler)
Risk Groups
| High Risk | Moderate Risk |
|---|---|
| Veterinarians working with mammals | Long-stay travellers to endemic areas |
| Bat handlers/researchers | Adventure travellers |
| Laboratory workers handling virus | Cycle touring in Asia/Africa |
| Animal control officers | Living in rural endemic areas |
Pathophysiology
Virology
- Virus: Lyssaviruses (family Rhabdoviridae)
- Classical rabies virus: Most common; found worldwide in animals
- Other Lyssaviruses: Australian bat (ABLV), European bat (EBLV), Duvenhage, Mokola
- Bullet-shaped virion; negative-sense single-stranded RNA
Transmission & Spread
- Inoculation: Virus deposited in tissue via bite/scratch
- Local replication: In muscle cells at wound site (days to months)
- Neural invasion: Binds nicotinic acetylcholine receptors at neuromuscular junction
- Centripetal spread: Travels via peripheral nerves to CNS (retrograde axonal transport)
- CNS replication: Brainstem, limbic system — causes encephalitis
- Centrifugal spread: Virus travels to salivary glands, skin, cornea
Incubation Factors
- Bite location: Face/neck = shorter incubation (closer to brain)
- Severity: Deep bites > superficial
- Viral load: Higher load = shorter incubation
- Host factors: Immunocompromise may accelerate
Neuropathology
- Negri bodies: Eosinophilic intracytoplasmic inclusions (pathognomonic but not always present)
- Perivascular cuffing and mononuclear infiltration
- Minimal neuronal necrosis (death from dysfunction, not destruction)
Clinical Presentation
Prodrome (2-10 days)
Clinical Forms
| Form | Frequency | Features |
|---|---|---|
| Furious (Encephalitic) | 80% | Hydrophobia, aerophobia, agitation, hypersalivation, autonomic dysfunction, intermittent lucidity |
| Paralytic (Dumb) | 20% | Ascending flaccid paralysis, like GBS; less agitation |
Cardinal Features (Furious Rabies)
| Feature | Description |
|---|---|
| Hydrophobia | Painful pharyngeal spasms when attempting to drink — pathognomonic |
| Aerophobia | Spasms triggered by air currents |
| Hypersalivation | "Foaming at the mouth" |
| Agitation/Aggression | Intermittent |
| Priapism | In males |
| Lucid intervals | Between episodes of agitation |
| Autonomic instability | Tachycardia, hypertension, arrhythmias |
Progression
Non-specific
Fever, malaise, headache, fatigue
Pain or paraesthesia at bite site (highly suggestive)
Common presentation.
Anxiety, agitation
Common presentation.
Clinical Examination
Exposure Assessment (Most Important)
- What animal? (dog, bat, wildlife)
- Where did the bite occur? (country, urban/rural)
- When? (time since exposure)
- What happened to the animal? (behaviour, still alive?)
- What wounds? (location, depth, number)
Clinical Examination in Suspected Rabies
- Wound inspection: Signs of infection, healing
- Neurological: Mental status, cranial nerves, tone, reflexes
- Autonomic signs: Tachycardia, hypertension, hypersalivation
- Hydrophobia test: Observe response to offered water
- Aerophobia test: Response to fanning/breeze
Investigations
Pre-Symptomatic (Exposure Assessment Only)
- No tests needed for PEP decision
- If in doubt, give PEP
Symptomatic Disease (Confirmation)
| Test | Sample | Notes |
|---|---|---|
| RT-PCR | Saliva, CSF, skin biopsy (nape of neck) | Most sensitive |
| Rabies virus antigen (DFA) | Skin biopsy (hair follicles) | Rapid, 70-80% sensitive |
| Antibodies (CSF) | CSF | Only present late in disease |
| Brain histology | Post-mortem | Negri bodies (pathognomonic) |
Note
- Multiple samples on different days increase sensitivity
- Negative tests do not exclude rabies early in disease
Classification & Staging
WHO PEP Categories
| Category | Type of Exposure | PEP Required |
|---|---|---|
| I | Touching/feeding animal, licks on intact skin | None |
| II | Minor scratches/abrasions without bleeding, licks on broken skin | Vaccine only |
| III | Transdermal bites/scratches, licks on mucous membranes, bat exposures | Vaccine + RIG |
UK Risk Assessment (PHE)
Based on:
- Country of exposure (endemic vs non-endemic)
- Type of animal
- Type of contact
- Animal behaviour and availability for observation
- Pre-exposure vaccination status
Management
Immediate Wound Care (Critical First Step)
- Wash thoroughly with soap/detergent and running water for 15+ minutes
- Apply antiseptic (povidone-iodine, alcohol-based)
- Do NOT suture wound primarily (delayed closure if needed)
- Tetanus prophylaxis if indicated
Post-Exposure Prophylaxis (PEP)
1. Rabies Vaccine:
- Essen Regimen: 1ml IM on days 0, 3, 7, 14 (4 doses for previously unvaccinated)
- Modified 2-dose: For previously vaccinated (days 0, 3)
- Site: Deltoid (NOT gluteal — poor absorption)
2. Rabies Immunoglobulin (RIG):
- Category III exposures only
- Dose: 20 IU/kg (human RIG) or 40 IU/kg (equine RIG)
- Infiltrate as much as anatomically feasible into/around wound(s)
- Remainder: IM at distant site from vaccine
- Timing: Day 0 only; not indicated after day 7
Pre-Exposure Prophylaxis (PrEP)
- For high-risk groups (vets, bat handlers, travellers to endemic areas with poor healthcare access)
- Regimen: 1ml IM on days 0, 7, 21-28 (3 doses)
- Simplifies PEP (vaccine only, no RIG needed)
UK Access to PEP
- Contact PHE Colindale 24/7 for advice
- RIG and vaccine held centrally
- Urgent cases: Casualty Hospital or local ID unit
Complications
Once Symptomatic
- Death (near-universal within 2-3 weeks)
- Rare survivors (Milwaukee Protocol): Profound neurological disability
PEP-Related
- Vaccine reactions: Local pain (common), systemic symptoms (rare)
- RIG reactions: Local pain; anaphylaxis rare
- Serum sickness: With equine RIG (5-10%)
Prognosis & Outcomes
Once Symptomatic
- Fatal in 100% of untreated cases
- ~15 documented survivors (most with profound disability)
- Milwaukee Protocol (induced coma + antivirals): Controversial, limited success
With Timely PEP
- Nearly 100% effective if started promptly with proper wound care
- Failures occur with delayed/incomplete PEP or massive viral inoculum
Key Prognostic Factors
- Time to PEP initiation: Earlier = better
- Wound washing: Reduces viral load significantly
- RIG infiltration: Critical for Category III
- Previous vaccination: Simplifies and accelerates PEP response
Evidence & Guidelines
Key Guidelines
- PHE Rabies: Guidelines on post-exposure treatment (2023)
- WHO Expert Consultation on Rabies (3rd Report, 2018)
- ACIP Recommendations for Human Rabies Prevention (2022)
Key Evidence
- World Rabies Day initiative aims for zero human deaths from dog-mediated rabies by 2030
- Meta-analysis: Wound washing alone reduces rabies risk by 90%
- Intradermal vaccination economically viable alternative in resource-limited settings
Patient & Family Information
What is Rabies?
Rabies is a deadly virus spread by animal bites or scratches. It infects the brain and is almost always fatal once symptoms appear. However, it is completely preventable with immediate treatment after a bite.
What to Do If Bitten by an Animal Abroad
- Wash the wound immediately with soap and running water for at least 15 minutes
- Apply antiseptic if available
- Seek medical help urgently — the same day if possible
- Tell the doctor where you were bitten and what animal bit you
Do I Need Treatment?
You may need rabies treatment if:
- You were bitten or scratched by an animal in Africa, Asia, or South America
- A bat touched you (even in the UK)
- You can't be sure the animal wasn't infected
Prevention
- Avoid touching animals abroad, especially stray dogs
- Consider vaccination before travel to high-risk areas
- Seek help immediately if bitten — don't wait to see if you develop symptoms
Resources
References
Primary Guidelines
- Public Health England. Rabies: post-exposure treatment (Human). 2023. gov.uk
- WHO. WHO Expert Consultation on Rabies: Third Report. WHO Technical Report Series No. 1012. 2018. who.int
- Manning SE, et al. Human Rabies Prevention — United States, 2022. MMWR Recomm Rep. 2022;71(2):1-33. PMID: 35552278
Key Studies
- Hemachudha T, et al. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol. 2002;1(2):101-109. PMID: 12849514
- Hampson K, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015;9(4):e0003709. PMID: 25881058