CHOLERA

- Contagious infection → caused by Vibrio cholerae → gastroenteritis and watery diarrhea

- Can cause electrolyte imbalance and rapid dehydration → fatal
- Gram negative, curved bacteria
- Oxidase +, grows in alkaline media (sensitive to acid), non-invasive, halophilic, genome
consists of 2 circular chromosomes
- Has pili and flagella → to move through GI tract
- Facultative anaerobe → can undergo respiratory and fermentative metabolism
- Reservoir: aquatic environments (saltwater, brackish)
- Fermentation: glucose, sucrose
- Transmission: fecal oral
- Common in developing countries and places lacking advanced sanitation and sewage
treatment facilities
People with ↓ gastric acidity or O-blood type → ↑ risk for severe infection

Virulence Factor
1. Cholera toxin
- Only toxigenic strains; responsible for pathogenesis of massive, watery diarrhea;
coded by filamentous bacteriophage (CTXΦ)
2. Other toxins that increase mucosal permeability:
- Zona occludens toxin (ZOT)
- Accessory cholera enterotoxin (ACE)
- WO7 toxin 17
3. Lipopolysaccharide (LPS): >200 serogroups → O1, O139 associated with cholera
epidemics
4. Motility: single polar flagellum (H-antigen)
5. Toxin-coregulated pilus (TCP)
- Present only in toxigenic strains → promoted adherence, aggregation of bacteria,
coded by genes in Vibrio pathogenicity island(VPI)
6. Mucinase: digests mucous layer of GI tract

Pathogenesis
- V.cholerae enters stomach → shuts down protein production (to conserve energy and
nutrients + to survive the acidic environment) → reach intestine, use flagella to move
towards intestinal walls → propel through the mucous layer on top of the epithelial cells
lining the intestine → attach to villi → colonization of small intensive via TCP → releases
cholera toxin
 ↑: causes symptoms like vomiting and voluminous amounts of watery diarrhea
containing extremely high concentrations of sodium, potassium, chloride, bicarbonate +
high levels of live V.cholerae → infect other individuals

Signs & Symptoms

- Incubation period: 28-48 hours
- Asymptomatic to severe depending on strain, inoculum concentration (≥108 → severe
form)
- Abrupt onset of profound watery diarrhea (grey, cloudy, flecked with mucous → rice
water stool), painless, without tenesmus, loss of 1 liter of fluid/hour in severe cases
- Moderate to severe vomiting, borborygmus, abdominal discomfort
- Dehydration: thirst, dry mucous membranes, decreased skin turgor, sunken eyes,
hypotension, weak/absent radial pulse, tachycardia, tachypnea, hoarse voice, oliguria
- Altered mental status: somnolence, restlessness, lethargy
- If untreated:
- Dehydration, hypovolemic shock in 4-12 hours, death in 18 hours to several days
- Renal failure secondary to hypovolemia
- Electrolyte imbalance: hypokalemia, metabolic acidosis
- ↓ bicarbonate → metabolic acidosis → kussmaul breathing
- ↓ potassium → muscle dysfunction (leg cramps, weakness, abnormal
heart rhythm)
- ↓ chloride and sodium → headache, poor balance, disorientation,
seizures, coma
- Pneumonia (esp in children) → due to aspiration of vomit
Diagnosis
- Stool samples → grow bacteria on thiosulfate-citrate-bile salts-sucrose agar
- Dark field microscopy/dipstick test of stool specimen for rapid confirmation in
non-endemic areas (detectable in stool for 1-2 weeks without antimicrobial therapy)
Lab:
- Hypoglycemia/hyperglycemia
- Hypercalcemia, hypermagnesemia, hyperphosphatemia
- ↑ hematocrit due to volume depletion

Treatment
- Replace lost water and electrolytes (rehydration salts)
- Mild-moderate diarrhea → may resolve in 3-7 days
- Extreme → antibiotics
- Tetracyclines, ciprofloxacin, ofloxacin, furazolidone or
trimethoprim-sulfamethoxazole

Prophylaxis
- WC-rBS (Dukoral) vaccine: monovalent inactivated oral cholera vaccine containing killed
whole cells of V.cholerae O1, additional recombinant cholera toxin B subunit
- BivWC (Shanchol) vaccine: bivalent inactivated oral vaccine containing killed whole cells
of V.cholerae O1, O139
- CVD 103-HgR/Vaxchora vaccine: attenuated oral vaccine derived from serogroup O1
classical Inaba strain