Cholera and Other Vibrioses¶

Chapter 173 | Part 5: Infectious Diseases · Part 5 – Infectious Diseases: Bacterial · Chapter 173

Key Clinical Points¶

Cholera is an acute diarrheal disease caused by V. cholerae serogroups O1 or O139, characterized by profound, rapidly progressive dehydration and death if untreated.
The hallmark 'rice-water' stool is nonbilious, gray, slightly cloudy fluid with flecks of mucus, no blood, and a fishy odor.
Fluid resuscitation is the cornerstone of therapy: Severe dehydration (>10% body weight) requires IV Ringer's lactate (100 mL/kg in first 3h; 6h for children <12 months).
Oral Rehydration Solution (ORS) is the standard for mild/moderate cases; WHO recommends low-osmolarity ORS (245 mOsm/L).
Antibiotics (azithromycin, doxycycline, erythromycin) are adjunctive to rehydration to reduce duration and volume of fluid loss.
V. parahaemolyticus is a leading cause of seafood-borne bacterial gastroenteritis and wound infections.
V. vulnificus is the most common cause of severe Vibrio infections in the US, associated with primary sepsis in patients with liver disease or hemochromatosis.
Zinc supplementation (10 mg/day for <6 months, 20 mg/day for 6-60 months) reduces volume and severity of diarrhea in children.
Non-O1/O139 V. cholerae strains do not produce cholera toxin and are distinguished by lack of agglutination in O1/O139 antiserum.
Doxycycline is contraindicated in pregnancy; azithromycin is the preferred alternative.

1. DEFINITION & OVERVIEW¶

• Cholera:

Definition: An acute diarrheal disease caused by V. cholerae serogroups O1 or O139, characterized by profound, rapidly progressive dehydration and death if untreated. • Vibrio Characteristics: ◦ Gram-negative rods with flagella ◦ Thrive in coastal waters and tidal rivers under moderate salinity conditions • Classification of Vibrio Species: ◦ V. cholerae: >200 serogroups based on LPS O antigens ◦ Serogroup O1 (Inaba/Ogawa biotypes) and O139: Epidemic-causing strains ◦ Non-O1/O139: Cause sporadic outbreaks; lack agglutination in O1/O139 antiserum ◦ V. parahaemolyticus: Seafood-borne gastroenteritis; wound infections ◦ V. vulnificus: Sepsis (especially in immunocompromised patients); wound infections, cellulitis ◦ V. alginolyticus: Wound infections (burned/immunocompromised), sepsis

2. EPIDEMIOLOGY¶

• Geographic Distribution: ◦ Native to Ganges delta; 7 global pandemics since 1817 ◦ 7th pandemic (El Tor biotype) began in Indonesia (1961) ◦ >95% of WHO-reported cases occur in Africa/Asia • Incidence: ◦ Annual global cases: 1–4 million ◦ Annual deaths: 20,000–140,000 • Risk Factors & Transmission: ◦ Primary route: Ingestion of contaminated water/feces ◦ No animal reservoir; human-to-human spread in endemic areas ◦ Risk factors: Poverty, poor sanitation, malnutrition, immunocompromised status (especially for V. vulnificus) ◦ Seasonal correlations: High temperatures, heavy rainfall, and flooding

3. ETIOLOGY & PATHOPHYSIOLOGY¶

• Pathogen: V. cholerae • Mechanism of Action (Cholera Toxin - CT): ◦ Structure: A (enzymatic) and B (binding) subunits ◦ Binding: B pentamer binds to GM1 ganglioside on epithelial cells ◦ Activation: A subunit ADP-ribosylates G protein → activates adenylate cyclase ◦ Effect: Cyclic AMP accumulation → inhibits sodium absorption + activates chloride secretion in intestinal crypts ◦ Result: Isotonic fluid accumulates in lumen → watery diarrhea • Virulence Factors: ◦ TCP (toxin-coregulated pilus): Facilitates colonization ◦ Pathogenicity islands: Contain virulence genes acquired via horizontal gene transfer

4. CLINICAL FEATURES¶

• Clinical Presentation: ◦ Sudden onset of painless, voluminous watery diarrhea (rice-water stool) ◦ Rice-water stool characteristics: Nonbilious, gray, slightly cloudy fluid with flecks of mucus; no blood; fishy odor ◦ Vomiting ◦ Absence of fever ◦ Muscle cramps due to electrolyte loss • Severity Indicators: ◦ Severe cases: Loss of >250 mL/kg in 24h → hypovolemic shock • Assessment of Dehydration (Table 173-1): ◦ None or mild: Thirst in some cases; <5% loss of total body weight ◦ Moderate: Sunken eyes, weak pulses, oliguria ◦ Severe: Unconsciousness, lethargy, or "floppiness"; weak or absent pulse; inability to drink; sunken eyes (sunken fontanelles in infants); >10% loss of total body weight • Laboratory Findings: ◦ Hemoconcentration: Elevated hematocrit ◦ Leukocytes: Mild neutrophilic leukocytosis ◦ Renal: Prerenal azotemia (elevated BUN/creatinine) ◦ Electrolytes: Normal electrolytes but low bicarbonate (<15 mmol/L) ◦ Acid-Base: Anion gap elevation (due to lactate/protein/phosphate); arterial pH ≈ 7.2

5. DIFFERENTIAL DIAGNOSIS¶

• Noncholera Vibrios (Table 173-5): ◦ V. parahaemolyticus: Seafood/seawater exposure → Gastroenteritis, wound infection ◦ Non-O1/O139 V. cholerae: Travel/shellfish → Gastroenteritis, otitis media, wound infection ◦ V. vulnificus: Shellfish/seawater → Sepsis (especially in cirrhosis/hemochromatosis), wound infection, cellulitis ◦ V. alginolyticus: Seawater → Wound infection (burned/immunocompromised), sepsis

6. INVESTIGATIONS & DIAGNOSIS¶

Clinical Suspicion: Identify patients ≥ 5 years with acute watery diarrhea in endemic areas OR severe dehydration/death in non-endemic regions
Microscopy: Collect fresh stool for dark-field microscopy (wet mount) to identify motile vibrios
Serotyping: Use specific antisera for serotyping
Culture: Isolate on TCBS agar or TTG agar; use Cary-Blair transport medium for delayed processing
Biochemical/Point-of-Care: Confirm oxidase positivity (all vibrios) and use point-of-care antigen-detection assays where lab facilities are lacking

7. MANAGEMENT & TREATMENT¶

Rehydration Strategy: Determine severity → select route • Mild/Moderate: Oral Rehydration Solution (ORS)
Standard: Low-osmolarity ORS (245 mOsm/L) (Table 173-3)
Preparation: If prepackaged is unavailable, use 3.5 g NaCl + 50g precooked rice cereal or 6 tsp sugar in 1 L water • Severe: IV Fluid Replacement
Solution: Ringer's lactate (or normal saline if unavailable)
Rate: 100 mL/kg in first 3h (or 6h for children <12 months) → start rapidly, then slow down
Total: 200 mL/kg in first 24h
Goal: Continue until patient is awake, can ingest ORS, and no longer has a weak pulse
Antibiotic Therapy:
Azithromycin: Adults 1 g single dose; children 20 mg/kg single dose
Doxycycline: Adults 300 mg single dose; children >8y 4–6 mg/kg single dose (Note: Contraindicated in pregnancy)
Erythromycin: Adults 250 mg QID x3d; children 12.5 mg/kg QID x3d
Ciprofloxacin: Adults 500 mg BID x3d; children 15 mg/kg BID x3d (if susceptible)
Zinc Supplementation:
Children <6mo: 10 mg/day for 10 days
Children 6–<60mo: 20 mg/day for 10 days
Effect: Reduces volume and severity of diarrhea
Monitoring:
Monitor for hypokalemia; replace potassium IV or orally as needed
Stool Electrolyte Reference (Table 173-4):
Adult Stool: Na+ 135, K+ 15, Cl- 100
Child Stool: Na+ 100, K+ 25, Cl- 90
Ringer's Lactate: K+ 4, Cl- 109, Base 30

8. PROGNOSIS & COMPLICATIONS¶

• Prognosis: ◦ Generally self-limiting and resolves in days with timely rehydration • Renal Failure: ◦ Cause: Prerenal azotemia from volume depletion ◦ Management: Reversible with fluid resuscitation; however, acute tubular necrosis may occur in severe cases

9. SPECIAL CONSIDERATIONS¶

• Immunocompromised Hosts: ◦ Higher risk of severe V. vulnificus infection (e.g., HIV, hemochromatosis) ◦ Poor response to antibiotics in HIV/AIDS patients ◦ Vaccination recommended for high-risk individuals • Prevention & Vaccination: ◦ Primary strategy: WASH (Water, Sanitation, Hygiene) ◦ Vaccines: BivWC (Shanchol), WC-rBS (Dukoral), and Vaxchora (live attenuated)

10. KEY PEARLS & CLINICAL TRAPS¶

• Rice-water stool: Pathognomonic but not always present in early stages; characterized by lack of blood and a fishy odor • Non-O1/O139 strains: Cause sporadic outbreaks; lack epidemic potential • Pregnancy: Doxycycline contraindicated; azithromycin preferred • Zinc: Avoid in adults with cholera • Ringer's Lactate: Standard for severe cases; contains base (30 mmol/L in children)

Reference Tables¶

TABLE 173-2 Treatment of Cholera, Based on Degree of Dehydration a¶

Harrison's 22e, p.1328

DEGREE OF DEHYDRATION, PATIENT’S AGE (WEIGHT)	TREATMENTb
None or Mild, but Diarrheac
<2 years	1/4–1/2 cup (50–100 mL) of ORS, to a maximum of 0.5 L/d
2–9 years	1/2–1 cup (100–200 mL) of ORS, to a maximum of 1 L/d
≥10 years	As much ORS as desired, to a maximum of 2 L/d
Moderatec,d
Severec
All ages and weights	Undertake IV fluid replacement with Ringer’s lactate (or, if not available, normal saline). Give 100 mL/kg in the first 3-h period (or the first 6-h period for children <12 months old); start rapidly, then slow down. Give a total of 200 mL/kg in the first 24 h. Continue until the patient is awake, can ingest ORS, and no longer has a weak pulse.

TABLE 173-3 Composition of World Health Organization Reduced- Osmolarity Oral Rehydration Solution (ORS) a,b…¶

Harrison's 22e, p.1328

CONSTITUENT	CONCENTRATION, mmol/L
Na+	75

TABLE 173-1 Assessing the Degree of Dehydration in Patients with Cholera

DEGREE OF DEHYDRATION	CLINICAL FINDINGS
None or mild, but diarrhea	Thirst in some cases; <5% loss of total body weight

TABLE 173-1 Assessing the Degree of Dehydration in Patients with Cholera¶

Harrison's 22e, p.1328

Cl–	65
Glucose	75
Severe	Unconsciousness, lethargy, or “floppiness”; weak or absent pulse; inability to drink; sunken eyes (and, in infants, sunken fontanelles); >10% loss of total body weight

TABLE 173-4 Electrolyte Composition of Cholera Stool and of Intravenous Rehydration Solution SUBSTANCE Stool Adult…¶

Harrison's 22e, p.1329

SUBSTANCE	CONCENTRATION, mmol/L
	NA+	K+	CL–	BASE
Stool
	135	15	100
Child	100	25	90	30
	130	4a	109

TABLE 173-5 Features of Selected Noncholera Vibrioses ORGANISM Vibrio parahaemolyticus Non-O1/O139 Vibrio cholerae…¶

Harrison's 22e, p.1330

ORGANISM	VEHICLE OR ACTIVITY	HOST AT RISK	SYNDROME
Vibrio parahaemolyticus	Shellfish, seawater	Normal	Gastroenteritis
	Seawater	Normal	Wound infection
	Shellfish, travel	Normal
	Seawater	Normal
Vibrio vulnificus	Shellfish	Immunosuppresseda	Sepsis, secondary cellulitis
	Seawater	Normal, immunosuppresseda	Wound infection, cellulitis
	Seawater	Normal
	Seawater	Burned, other immunosuppressed