Cholera

Cholera is an acute, severe, secretory (toxigenic) diarrhoeal disease caused by Vibrio cholerae, characterised by painless profuse "rice-water" stools that can kill a previously healthy adult within hours through hypovolaemic shock. It remains a sentinel marker of poor sanitation and unsafe water, and is a perennial favourite in Community Medicine for its El Tor biotype, the WHO ORS formula, and outbreak control.

High-yield: Cholera is the classic example of a water-borne, faeco-orally transmitted, toxin-mediated, non-inflammatory secretory diarrhoea — the gut mucosa is histologically near-normal despite litres of fluid loss.

Definition & the organism

Vibrio cholerae is a Gram-negative, comma-shaped (curved) bacillus, motile by a single polar (monotrichous) flagellum giving rapid "darting/shooting-star" motility on dark-field microscopy. It is oxidase-positive, non-halophilic, and grows on alkaline media (it tolerates pH up to ~9, which is exploited in selective media).

Of the >200 O-serogroups, only two cause epidemic cholera:

• O1 — the cause of the classical pandemics, divided into biotypes Classical and El Tor, and further into serotypes Ogawa, Inaba, and Hikojima.
• O139 (Bengal) — emerged in 1992 from Madras (Chennas)/Bangladesh, the first non-O1 to cause epidemics; it has a capsule (O1 does not).

Non-O1/non-O139 strains (NAG vibrios) may cause sporadic gastroenteritis but not epidemic cholera.

High-yield: The current (7th) pandemic is caused by the El Tor biotype. O139 is the only non-O1 serogroup capable of causing epidemics and was named "Bengal" after the Bay of Bengal where it arose.

Culture & media (often asked)

Purpose	Medium	Key point
Transport	VR (Venkataraman–Ramakrishnan) medium	Alkaline; best transport medium for stool
Enrichment	Alkaline peptone water (pH 8.6)	Vibrio outgrows other flora; subculture in 6–8 h
Selective/plating	TCBS agar (thiosulphate-citrate-bile salt-sucrose)	V. cholerae ferments sucrose → yellow colonies
Older selective	Monsur's / bile-salt agar	Translucent colonies with halo

El Tor vs Classical — the must-know table

This comparison is the single most repeated Cholera fact in NEET PG.

Feature	Classical biotype	El Tor biotype
Haemolysis (sheep RBC)	Non-haemolytic	Haemolytic (variable now)
Voges–Proskauer (VP)	Negative	Positive
Polymyxin B (50 U) sensitivity	Sensitive	Resistant
Chick RBC agglutination	No	Yes
Group IV cholera phage susceptibility	Susceptible	Resistant
Classical phage IV	Susceptible	Resistant
Ratio of cases : carriers	~1:5 to 1:10	~1:30 to 1:100
Severity	More severe disease	Often milder/subclinical
Survival in environment	Poor	Superior — survives longer in water & host
Pandemic	6 earlier pandemics	7th (current) pandemic

High-yield: El Tor survival advantage — El Tor produces more carriers, more subclinical infections, survives longer in water/environment, and persists longer in the host. This higher carrier-to-case ratio makes it harder to eradicate and lets it spread silently. This is the single most tested "why El Tor replaced Classical" concept.

Mnemonic for El Tor positives — "El Tor Votes Politely, Plays Chicken, Hates Polymyxin":

• Voges–Proskauer positive
• Polymyxin B resistant
• Chicken RBC agglutination positive
• Haemolytic (classically), phage IV resistant

Etiology & pathophysiology

The toxin (CTX / choleragen)

The disease is mediated entirely by the cholera enterotoxin (CT / choleragen), encoded by the ctxAB genes carried on the CTXφ bacteriophage (lysogenic conversion). Colonisation requires the toxin-coregulated pilus (TCP), which is also the receptor for the CTX phage.

The toxin is an A-B subunit exotoxin (one A subunit, five B subunits):

1. B subunits (pentamer) bind irreversibly to GM1 ganglioside receptors on enterocytes of the small intestine. →
2. A1 subunit enters the cell and ADP-ribosylates the Gsα protein, locking adenylate cyclase in the "on" state. →
3. Sustained rise in intracellular cyclic AMP (cAMP). →
4. cAMP drives active secretion of Cl⁻ (and HCO₃⁻) via the CFTR channel and blocks Na⁺ absorption. →
5. Massive isotonic efflux of water and electrolytes into the lumen, overwhelming colonic reabsorption. →
6. Rice-water stool, isotonic dehydration, metabolic acidosis (bicarbonate loss), hypokalaemia.

High-yield: Cholera toxin → ↑ cAMP (via Gs/adenylate cyclase). Contrast: heat-stable toxin of ETEC → ↑ cGMP. The gut wall stays intact (no invasion) — hence no blood, no pus, no fever in classic cholera.

Mechanism of rice-water stool

The fluid lost is essentially an isotonic ultrafiltrate of plasma: it contains flecks of mucus and shed epithelial cells (giving the rice-water/"rice-washing" appearance), has little odour or a fishy odour, no bile, and is rich in bicarbonate (~2× plasma) and potassium (~4–5× plasma) but iso-osmolar with plasma. This electrolyte profile explains the resulting acidosis and hypokalaemia, and dictates ORS/IV fluid composition.

Infective dose & host factors

• The infective dose is high — ~10⁸–10¹¹ organisms because vibrios are acid-labile; achlorhydria, antacids, partial gastrectomy, and H₂ blockers lower the dose dramatically and raise risk.
• Blood group O carries a higher risk of severe cholera (cholera gravis).
• Breast-feeding is protective in infants.

Clinical features

After an incubation of a few hours to 5 days (usually 1–2 days):

• Stage of evacuation: abrupt painless watery diarrhoea + effortless vomiting; stool rapidly becomes the classic rice-water stool. Purging up to 0.5–1 litre/hour.
• Stage of collapse (algid stage): dehydration, sunken eyes, washerwoman's hands, feeble/absent pulse, hypotension, anuria, painful muscle cramps (electrolyte loss), subnormal temperature, "voice of cholera" (husky). Sensorium usually clear until terminal.
• Stage of recovery / reaction: if rehydrated in time, recovery is dramatic and complete.

High-yield: Cholera causes isotonic dehydration with metabolic acidosis and hypokalaemia. Death is from hypovolaemic shock and acidosis, often within hours — making it the most rapidly dehydrating diarrhoea. Stool can lose more K⁺ and HCO₃⁻ than plasma.

WHO dehydration assessment

Sign	No dehydration	Some dehydration	Severe dehydration
General condition	Well, alert	Restless, irritable	Lethargic/unconscious
Eyes	Normal	Sunken	Very sunken, dry
Thirst	Drinks normally	Thirsty, drinks eagerly	Drinks poorly/unable
Skin pinch	Goes back quickly	Goes back slowly	Goes back very slowly (>2 s)
Fluid deficit	<5%	5–10%	>10%
WHO plan	Plan A	Plan B	Plan C (IV)

Diagnosis & investigation of choice

• Clinical/epidemiological: a sudden cluster of severe watery diarrhoea with rapid dehydration in an endemic area is presumptive cholera.
• Stool microscopy: dark-field/hanging-drop shows characteristic "darting/shooting-star" motility, abolished by specific antiserum — a rapid bedside clue.
• Investigation of choice / confirmatory: stool culture on TCBS agar (yellow sucrose-fermenting colonies) after enrichment in alkaline peptone water. Culture allows biotyping, serotyping, and antibiotic sensitivity.
• Rapid tests: dipstick/RDT for O1 and O139 antigens — useful for outbreak detection, but a positive RDT must be confirmed by culture.
• Stool shows scanty cells / no pus cells (non-inflammatory), distinguishing it from invasive dysentery.

High-yield: Investigation of choice = stool culture on TCBS. Transport medium of choice = VR fluid (or Cary–Blair). Enrichment = alkaline peptone water. Dark-field motility + immobilisation by antiserum is the quick presumptive test.

Management — the drugs and fluids that get asked

1. Rehydration is everything

The cornerstone is fluid and electrolyte replacement; antibiotics are adjunctive.

• Plan A (no dehydration): home fluids + ORS after each loose stool.
• Plan B (some dehydration): ORS 75 ml/kg over 4 hours, then reassess.
• Plan C (severe dehydration): IV Ringer's lactate is the fluid of choice (closely matches stool losses; contains lactate → bicarbonate). Give 100 ml/kg: in adults 30 ml/kg in first 30 min, then 70 ml/kg over 2.5 h; in infants spread over 6 h. Add ORS once the patient can drink. Normal saline is acceptable if RL unavailable (but lacks K⁺ and base).

High-yield: IV fluid of choice in severe cholera = Ringer lactate. Add potassium and treat acidosis as needed; switch to ORS as soon as the patient can drink.

2. WHO ORS — the formula you must memorise

WHO introduced the low-osmolarity ORS (2002, reduced-osmolarity), now the global standard.

Component	Concentration (mmol/L)	Note
Sodium (Na⁺)	75	Reduced from old 90
Glucose (anhydrous)	75	Drives Na⁺–glucose co-transport (SGLT1)
Potassium (K⁺)	20	Replaces stool K⁺ loss
Chloride (Cl⁻)	65
Citrate	10	Corrects acidosis (replaced bicarbonate)
Total osmolarity	245 mOsm/L	"Low/reduced osmolarity" ORS

Mnemonic for the four salts in a sachet: glucose (anhydrous) 13.5 g, trisodium citrate 2.9 g, sodium chloride 2.6 g, potassium chloride 1.5 g per litre.

High-yield (most-tested numbers): Low-osmolarity WHO ORS = Na 75, glucose 75, K 20, Cl 65, citrate 10; total osmolarity 245 mOsm/L. The Na : glucose molar ratio is 1:1, which maximises sodium-glucose co-transport (SGLT1) — the physiologic basis of ORS. Citrate replaced bicarbonate for better shelf stability.

In severe purging, cholera saline / rice-based ORS may further reduce stool volume.

3. Antibiotic (drug of choice)

Antibiotics shorten the duration of diarrhoea, reduce stool volume by ~50%, and curtail the carrier state — they are an adjunct, not a substitute for fluids. Reserve for moderate–severe disease.

• Drug of choice (adults): a single dose of doxycycline 300 mg.
• Azithromycin (single 1 g; 20 mg/kg in children) is preferred in pregnancy and children and where tetracycline resistance exists.
• Alternatives: ciprofloxacin (resistance now widespread), co-trimoxazole.

High-yield: Antibiotic of choice = doxycycline single dose; in pregnancy/children = azithromycin. Zinc 20 mg/day for 10–14 days is added in children (10 mg/day if <6 months) to reduce duration and severity.

Complications

• Hypovolaemic shock and acute renal failure (acute tubular necrosis) from prolonged hypoperfusion — the leading killers.
• Severe metabolic acidosis (bicarbonate loss).
• Hypokalaemia → arrhythmias, paralytic ileus, muscle weakness.
• Hypoglycaemia (especially children) — a major cause of death; check sugar.
• Pregnancy: abortion / foetal loss.
• Pulmonary oedema from over-zealous saline without correcting acidosis.

Key differentials

Condition	Distinguishing features
ETEC (traveller's diarrhoea)	LT toxin (cAMP, like cholera) ± ST (cGMP); usually milder, self-limited
Rotavirus / viral gastroenteritis	Children <2 y, low-grade fever, vomiting, winter; no rice-water stool
Bacillary dysentery (Shigella)	Blood + mucus, fever, tenesmus, pus cells — invasive/inflammatory
V. parahaemolyticus	Halophilic; seafood; self-limited; Kanagawa phenomenon
C. difficile	Antibiotic-associated, pseudomembranous colitis
Arsenic / mushroom poisoning	Toxic history, no epidemic clustering

Epidemiology & outbreak control

• Reservoir: humans (cases + carriers); El Tor also persists in brackish/estuarine water with copepods/plankton.
• Transmission: faeco-oral via contaminated water (chief vehicle), food, flies, fingers, fomites. Endemic in the Gangetic delta of India and Bangladesh ("homeland of cholera").
• Carriers: convalescent, contact, and (rarely) chronic carriers (gallbladder reservoir — the historic "cholera carrier" akin to typhoid). Carrier identification is central to El Tor control.

Stepwise outbreak control (a classic short-note)

Verify diagnosis → Notify (cholera is internationally notifiable under IHR) → Confirm an outbreak (compare with baseline) → Define & search for cases → Line listing & spot map → Treat cases (rehydration + antibiotic) → Disinfect/ensure safe water → Health education → Continue surveillance until 2 incubation periods pass with no new case.

Control pillars:

• Safe water: chlorinate water supplies; for wells use bleaching powder (≥0.5 mg/L residual chlorine); promote boiling.
• Sanitation: safe excreta disposal, hand hygiene, food safety.
• Treatment camps with ORS corners; early rehydration cuts case-fatality from >50% to <1%.
• Vaccine: modern oral killed whole-cell vaccines (Dukoral with B-subunit; Shanchol / Euvichol — bivalent O1+O139) are WHO-recommended for outbreak and endemic settings. The old parenteral killed vaccine is obsolete (poor, short protection, not recommended).
• Chemoprophylaxis: mass chemoprophylaxis is NOT recommended; selective doxycycline only for close household contacts in some settings.

High-yield: Cholera is a notifiable disease under the International Health Regulations (IHR 2005). Modern control uses oral killed vaccines (Shanchol/Dukoral); the injectable vaccine and mass chemoprophylaxis are not recommended. Safe water + ORS are the mainstays.

Recently asked / exam angle

• El Tor vs Classical differentiation (VP, polymyxin B resistance, chick-cell agglutination, phage IV, haemolysis) — the most repeated MCQ stem.
• El Tor survival advantage / higher carrier-to-case ratio as the reason it replaced Classical and persists.
• WHO low-osmolarity ORS composition — match Na 75 / glucose 75 / K 20 / citrate 10 / total 245 mOsm/L; "Na:glucose 1:1" and SGLT1 co-transport rationale.
• Mechanism of toxin — A-B subunit, GM1 ganglioside, ADP-ribosylation of Gsα, ↑cAMP (vs ETEC-ST ↑cGMP).
• O139 Bengal — first epidemic non-O1, capsulated, emerged 1992.
• Investigation/transport media — TCBS (yellow colonies), VR medium, alkaline peptone water.
• Drug of choice — single-dose doxycycline; azithromycin in pregnancy/children; Ringer lactate for severe dehydration.
• Outbreak control steps and the fact cholera is IHR-notifiable.

Rapid revision

1. V. cholerae = Gram-negative comma-shaped bacillus, single polar flagellum, "darting" dark-field motility, oxidase-positive.
2. Epidemic serogroups = O1 (Classical & El Tor) and O139 (Bengal, capsulated, 1992); current 7th pandemic = El Tor.
3. El Tor = VP positive, polymyxin B resistant, chick-cell agglutination positive, haemolytic, phage IV resistant — and survives better with a high carrier:case ratio.
4. Toxin = A-B exotoxin (CTXφ phage, ctxAB) → B binds GM1 ganglioside, A1 ADP-ribosylates Gsα → ↑ cAMP → Cl⁻/water secretion via CFTR.
5. Rice-water stool = isotonic, mucus flecks, no bile, bicarbonate- and potassium-rich, no blood/pus.
6. Dehydration is isotonic with metabolic acidosis + hypokalaemia + hypoglycaemia; death from hypovolaemic shock.
7. Investigation of choice = stool culture on TCBS (yellow colonies); transport = VR medium; enrichment = alkaline peptone water (pH 8.6).
8. WHO low-osmolarity ORS = Na 75, glucose 75, K 20, Cl 65, citrate 10; 245 mOsm/L, Na:glucose 1:1 (SGLT1).
9. Severe dehydration → IV Ringer lactate 100 ml/kg; plus single-dose doxycycline (azithromycin in pregnancy/children) and zinc in children.
10. Antibiotics are adjunctive — they cut stool volume ~50% and shorten the carrier state but never replace rehydration.
11. Cholera is notifiable under IHR 2005; modern prevention uses oral killed vaccines (Shanchol, Dukoral); injectable vaccine and mass chemoprophylaxis are obsolete/not recommended.
12. Outbreak control = safe (chlorinated) water + sanitation + ORS corners + surveillance; case-fatality falls from >50% untreated to <1% with prompt rehydration.