Overview
Cholera
1. Clinical Overview
Summary
Cholera is an acute secretory diarrhoeal disease caused by toxigenic Vibrio cholerae (serogroups O1 and O139). It is transmitted via faecal-oral route through contaminated water or food. The cholera toxin causes massive secretion of water and electrolytes into the intestinal lumen, leading to "rice water" stools and potentially fatal dehydration within hours. Cholera remains endemic in parts of Asia, Africa, and Haiti. Treatment is primarily aggressive fluid replacement (ORS or IV Ringer's lactate). Antibiotics shorten duration but fluids save lives. Mortality approaches 50% untreated but <1% with appropriate rehydration.
Key Facts
- Cause: Vibrio cholerae O1 or O139 (toxigenic strains)
- Transmission: Faecal-oral (contaminated water, seafood)
- Incubation: 12 hours to 5 days
- Fluid Loss: Up to 1 litre per hour (20L/day possible)
- Classic Stool: "Rice water" - profuse, watery, odourless
- Treatment Priority: FLUIDS, FLUIDS, FLUIDS (ORS or IV)
- Mortality: 50% untreated → <1% with rehydration
Clinical Pearls
"Cholera Kills by Dehydration, Not Infection": The bacterium doesn't invade the mucosa. Death is from hypovolaemic shock, not sepsis. Replace fluids and the patient survives.
"Rice Water Stool is Pathognomonic": The classic profuse, watery, flecked stool with fishy odour is virtually diagnostic in endemic areas.
"ORS is WHO's Greatest Invention": Oral rehydration solution has saved more lives than any other medical innovation. Glucose-sodium co-transport rescues intestinal absorption.
"Match Output with Input": In severe cholera, measure stool output and replace volume-for-volume. Inadequate replacement = death.
2. Epidemiology
Global Burden
- 1.3-4 million cases annually
- 21,000-143,000 deaths annually
- Endemic in South Asia, sub-Saharan Africa, Haiti
- Associated with poverty, lack of sanitation
Outbreaks
- Occur after natural disasters, conflict, population displacement
- Waterborne spread
- Can spread explosively in susceptible populations
Risk Factors
| Factor | Notes |
|---|---|
| Contaminated water supply | Main route |
| Seafood (especially shellfish) | Bioconcentrates V. cholerae |
| Low gastric acidity | PPI use, malnutrition |
| Blood group O | More severe disease |
| Poverty/poor sanitation | Endemic settings |
| Travel to endemic area |
Serogroups
- O1 (El Tor and Classical biotypes) - 99% of cases
- O139 (Bengal) - Emerged 1992, limited spread
3. Pathophysiology
Mechanism of Disease
┌──────────────────────────────────────────────────────────┐
│ CHOLERA TOXIN MECHANISM │
├──────────────────────────────────────────────────────────┤
│ │
│ 1. V. cholerae colonises small intestine │
│ │
│ 2. Cholera toxin (CT) released │
│ - A-B toxin structure │
│ - B subunit binds GM1 ganglioside │
│ - A subunit enters cell │
│ │
│ 3. A subunit ADP-ribosylates Gs protein │
│ → Permanent activation of Adenylate Cyclase │
│ │
│ 4. ↑ Intracellular cAMP │
│ → CFTR channel opens │
│ → Chloride secretion into lumen │
│ → Sodium and WATER follow │
│ │
│ 5. Massive secretory diarrhoea │
│ → Up to 1L/hour fluid loss │
│ → Isotonic dehydration │
│ → Hypovolaemic shock → Death │
│ │
└──────────────────────────────────────────────────────────┘
Why ORS Works
- Sodium-glucose cotransporter (SGLT1) remains intact
- Glucose enhances sodium absorption
- Water follows sodium
- Bypasses the secretory defect
Key Electrolyte Losses
- Sodium, potassium, bicarbonate (hypokalaemia, metabolic acidosis)
- Stool electrolyte composition similar to plasma
4. Clinical Presentation
Spectrum of Disease
Symptoms
| Feature | Description |
|---|---|
| Diarrhoea | Sudden onset, profuse, watery, effortless |
| Rice water stool | Grey-white, flecked, fishy odour |
| Volume | Up to 1L/hour; 20L/day possible |
| Vomiting | Common, watery |
| Cramps | Muscle cramps from electrolyte loss |
| No fever | Usually afebrile (toxin, not invasion) |
| No abdominal pain | Usually painless |
Signs of Dehydration
| None/Mild | Moderate | Severe |
|---|---|---|
| Alert | Restless, irritable | Lethargic, unconscious |
| Normal eyes | Sunken eyes | Deeply sunken |
| Moist mucosa | Dry mouth | Very dry |
| Drinks normally | Thirsty, drinks eagerly | Unable to drink |
| Skin pinch retracts | Retracts slowly (<2s) | Retracts very slowly (>s) |
| Normal pulse | Rapid pulse | Feeble or absent pulse |
| <5% body weight | 5-10% body weight | >0% body weight |
75% asymptomatic or mild diarrhoea
Common presentation.
25% moderate-severe illness
Common presentation.
5% severe "cholera gravis"
Common presentation.
5. Clinical Examination
Assessment (WHO Guidelines)
- Mental status: Alert → Restless → Lethargic
- Eyes: Normal → Sunken → Deeply sunken
- Mucous membranes: Moist → Dry → Parched
- Skin turgor: Pinch skin of abdomen
- Radial pulse: Present and strong → Weak → Absent
- Respiratory pattern: Normal → Deep (acidosis)
Signs of Severe Dehydration (Shock)
- Cold, clammy extremities
- Cyanosis
- Weak or absent radial pulse
- Hypotension
- Rapid, deep breathing (Kussmaul)
- Altered consciousness
6. Investigations
Clinical Diagnosis
- Suspected on clinical grounds in endemic/epidemic setting
- Profuse watery diarrhoea + severe dehydration + exposure risk
Laboratory Confirmation
| Test | Purpose |
|---|---|
| Stool culture | Gold standard; TCBS agar (yellow colonies) |
| Rapid test (RDT) | Crystal VC dipstick; field use |
| Darkfield microscopy | Darting motility (research) |
| PCR | Confirmation, outbreak investigation |
Supportive Tests
| Test | Findings |
|---|---|
| U&E | ↑ Urea (prerenal), ↓ K+ |
| ABG | Metabolic acidosis (↓ HCO3-) |
| Glucose | Hypoglycaemia (children) |
7. Management
Immediate Assessment and Rehydration
┌──────────────────────────────────────────────────────────┐
│ CHOLERA TREATMENT: FLUIDS SAVE LIVES │
├──────────────────────────────────────────────────────────┤
│ │
│ SEVERE DEHYDRATION (SHOCK): │
│ ───────────────────────── │
│ • IV Ringer's Lactate (Hartmann's) STAT │
│ • Adults: 30ml/kg in first 30 min, then 70ml/kg over 2.5h│
│ • Monitor: Urine output, pulse, consciousness │
│ • Switch to ORS once able to drink │
│ │
│ MODERATE DEHYDRATION: │
│ ───────────────────── │
│ • ORS 75ml/kg over 4 hours │
│ • Reassess every 1-2 hours │
│ • IV if worsening or unable to tolerate oral │
│ │
│ MILD/NO DEHYDRATION: │
│ ──────────────────── │
│ • ORS after each stool (10-20ml/kg) │
│ • Continue feeding │
│ │
│ MATCH OUTPUT: Replace stool volume with ORS │
│ │
└──────────────────────────────────────────────────────────┘
Oral Rehydration Solution (ORS)
- WHO-ORS (reduced osmolarity):
- Sodium 75 mmol/L
- Glucose 75 mmol/L
- Potassium 20 mmol/L
- Citrate 10 mmol/L
- If no ORS: 6 teaspoons sugar + ½ teaspoon salt in 1L water
Antibiotics
| Antibiotic | Dose | Notes |
|---|---|---|
| Doxycycline | 300mg single dose | First-line adult |
| Azithromycin | 1g single dose | Pregnancy, children |
| Ciprofloxacin | 1g single dose | Alternative |
- Antibiotics reduce duration and stool volume by 50%
- NOT a substitute for fluid replacement
- Resistance emerging (check local patterns)
Zinc Supplementation (Children)
- 20mg daily for 10-14 days
- Reduces duration and severity
8. Complications
From Dehydration
- Hypovolaemic shock
- Acute kidney injury (prerenal)
- Multi-organ failure
- Death (within hours if untreated)
Electrolyte Disturbances
- Hypokalaemia → Muscle weakness, arrhythmias
- Metabolic acidosis → Kussmaul breathing
- Hypoglycaemia (especially children)
Other
- Aspiration (vomiting)
- Seizures (hypoglycaemia in children)
- Pregnancy complications (miscarriage, preterm labour)
9. Prognosis & Outcomes
Mortality
| Scenario | Mortality |
|---|---|
| Untreated severe cholera | 50% |
| With ORS alone | 5-10% |
| With IV + ORS | <1% |
Recovery
- Rapid with rehydration
- Most recover within 3-6 days
- No long-term sequelae typically
Immunity
- Infection provides some immunity
- Short-lived (~3 years)
- Reinfection possible
10. Evidence & Guidelines
Key Guidelines
- WHO Guidelines on Cholera (2017)
- MSF Clinical Guidelines: Cholera
- CDC Cholera Treatment and Prevention
Key Evidence
ORS Revolution
- WHO ORS has saved 50+ million lives since 1970s
- Reduced cholera mortality from 50% to <1%
Low-Osmolarity ORS
- RCT: Reduced stool output by 20%
- Now standard WHO formulation
Prevention
- Safe water and sanitation (primary)
- Oral cholera vaccines (OCV): Dukoral, Shanchol
- 60-85% protection for 2-3 years
- Used for outbreak response
11. Patient/Layperson Explanation
What is Cholera?
Cholera is an infection of the intestines caused by a bacterium found in contaminated water or food. It causes very severe watery diarrhoea that can lead to dangerous dehydration within hours.
How Do You Get It?
- Drinking contaminated water
- Eating food washed in unsafe water
- Eating undercooked shellfish from contaminated waters
Cholera is found in parts of Africa, Asia, and Haiti where clean water is limited.
What Are the Symptoms?
- Sudden, profuse watery diarrhoea (sometimes called "rice water")
- Vomiting
- Muscle cramps
- Feeling weak and dizzy from fluid loss
How is it Treated?
The key treatment is replacing lost fluids:
- Oral rehydration solution (ORS) - a special drink with salts and sugar
- Intravenous (IV) fluids if very dehydrated
- Antibiotics may be given to shorten the illness
How Can You Prevent It?
When travelling to affected areas:
- Only drink bottled or boiled water
- Avoid ice in drinks
- Eat only thoroughly cooked food
- Avoid raw shellfish
- Wash hands frequently
Vaccines are available for high-risk travellers.
12. References
Primary Guidelines
- World Health Organization. The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers. 2017.
- WHO. Cholera Vaccines: Position Paper. Weekly Epidemiological Record. 2017;92(34):477-500.
Key Studies
- Mahalanabis D, et al. Oral fluid therapy of cholera among Bangladesh refugees. Johns Hopkins Med J. 1973;132(4):197-205.
- CHOICE Study Group. Multicentric, randomized, double-blind clinical trial to evaluate efficacy and safety of a reduced osmolarity oral rehydration salts solution. Pediatrics. 2001;107(4):613-618.