Cholera

Acute, severe watery diarrheal illness caused by toxigenic Vibrio cholerae (serogroups O1 and O139), a gram-negative comma-shaped bacterium. Cholera toxin activates adenylate cyclase in intestinal epithelial cells, increasing cAMP, causing massive efflux of chloride and water into the gut lumen ("rice water stools") — a secretory, non-inflammatory diarrhea capable of causing profound dehydration within hours. Transmitted via fecal-oral route, primarily contaminated water/food. Endemic in areas with poor water/sanitation infrastructure; epidemic potential in outbreaks/humanitarian crises.

Classified by:

• O1 biotypes: classical (historically more severe) and El Tor (current dominant pandemic strain, milder but more prone to asymptomatic carriage) — each with Ogawa/Inaba/Hikojima serotypes

• O139: emerged 1992, largely confined to South/Southeast Asia

• Clinical spectrum: asymptomatic/mild (majority of infections) to severe cholera gravis (profuse watery diarrhea, rapid dehydration, shock)

• Incubation: hours to 5 days (usually 1–2 days)

• Sudden onset profuse, painless, watery diarrhea — classic "rice water stool" (pale, flecks of mucus, fishy odor, no blood/inflammatory cells)

• Vomiting (usually non-bilious, follows diarrhea onset)

• Absence of fever/abdominal pain in most cases (distinguishes from inflammatory diarrheas — presence of high fever or bloody stool should prompt reconsideration of diagnosis)

• Rapid, severe fluid/electrolyte loss — can exceed 1L/hour in severe cases, leading to dehydration within hours

• Dehydration assessment (WHO classification — critical for triage):

• No dehydration: <5% fluid loss, alert, normal thirst, normal skin turgor

• Some dehydration: 5–10% loss, restless/irritable, sunken eyes, drinks eagerly/thirsty, skin pinch retracts slowly

• Severe dehydration: >10% loss, lethargic/unconscious, sunken eyes, unable to drink or drinks poorly, skin pinch retracts very slowly (>2 sec), weak/absent radial pulse, hypotension, tachycardia, oliguria/anuria

• Complications of severe fluid/electrolyte loss: hypovolemic shock, acute kidney injury, hypokalemia (muscle weakness, cardiac arrhythmia, ileus), hypoglycemia (esp. children), metabolic acidosis, muscle cramps

Primarily clinical, especially in known endemic/outbreak setting: acute profuse watery diarrhea in a patient ≥2 years old (WHO clinical case definition), or any age during a declared outbreak.

Confirmatory testing (for surveillance/outbreak confirmation, not required to initiate treatment):

• Stool microscopy: characteristic darting motility of V. cholerae on dark-field/phase-contrast microscopy

• Stool culture on selective media (TCBS agar — thiosulfate citrate bile salts sucrose) — gold standard, also allows antibiotic sensitivity testing

• Rapid diagnostic tests (RDTs — dipstick immunochromatographic assays): useful for field/outbreak screening, lower sensitivity/specificity than culture

• PCR: identifies toxigenic strains, used in reference labs

Electrolytes/renal function: U&E, creatinine, glucose (especially in children) — assess severity of derangement, guide correction, though treatment should not be delayed awaiting results in clinically severe dehydration.

Differentials: other secretory/watery diarrheal illnesses — ETEC (enterotoxigenic E. coli, clinically similar), rotavirus (children), other Vibrio species, food poisoning (S. aureus, B. cereus toxin-mediated), severe shigellosis (usually bloody/inflammatory, differs from cholera's watery picture).

Rehydration is the cornerstone of treatment — mortality can be reduced from >50% (untreated severe cholera) to <1% with prompt, adequate fluid replacement.

Rehydration (WHO protocol, by severity):

• No dehydration: ORS after each loose stool — <2y: 50–100mL, 2–9y: 100–200mL, ≥10y/adults: as much as wanted, minimum 200-400mL after each stool

• Some dehydration: ORS 75mL/kg over 4 hours, reassess; use ORS solution (WHO low-osmolarity formula — Na 75mmol/L, glucose 75mmol/L, K 20mmol/L, citrate 10mmol/L)

• Severe dehydration: IV fluids immediately — Ringer's lactate (preferred) or normal saline if RL unavailable

• Adults: 100mL/kg total — 30mL/kg over first 30 min, then remaining 70mL/kg over next 2.5 hours

• Children <1 year: 100mL/kg — 30mL/kg over first hour, then 70mL/kg over next 5 hours

• Reassess every 15–30 min; repeat bolus if radial pulse remains weak/absent

• Switch to ORS as soon as patient can drink and dehydration improving (typically after IV phase, continue ORS to replace ongoing losses)

• Monitor: hydration status, urine output, stool/vomit losses (use cholera cot with graduated collection if available) — replace ongoing losses volume-for-volume with ORS

Antibiotics (adjunct — reduces duration of diarrhea, volume of stool loss, and duration of V. cholerae excretion; not a substitute for rehydration):

• Indicated for moderate-severe dehydration

• Doxycycline 300mg single dose (adults) — first-line where sensitivity confirmed

• Azithromycin 1g single dose (adults), 20mg/kg single dose (children) — preferred in pregnancy and children, and where doxycycline resistance suspected

• Ciprofloxacin: alternative, resistance increasingly common — check local sensitivity patterns

• Local antibiotic resistance surveillance should guide choice given increasing resistance globally

Zinc supplementation (children <5 years, per WHO/UNICEF diarrhea management): 10mg/day (<6 months) or 20mg/day (≥6 months) for 10–14 days — reduces duration/severity and reduces recurrence risk in subsequent months

Nutrition: continue breastfeeding throughout; resume normal diet as soon as tolerated (no prolonged fasting)

Public health measures (essential, outbreak control):

• Case reporting — cholera is a notifiable disease

• Safe water provision (chlorination, boiling), improved sanitation, hygiene promotion (handwashing)

• Oral cholera vaccine (OCV — killed whole-cell, e.g., Dukoral, Shanchol/Euvichol) for outbreak control and endemic high-risk populations; not a substitute for WASH (water, sanitation, hygiene) interventions

• Isolation/cohorting of cases in treatment centers during outbreaks, safe disposal of waste

Admission criteria: all severe dehydration, some dehydration with comorbidities/extremes of age/inability to tolerate ORS, or inadequate home/outbreak-setting support for ORS management.