Cholera

Definition, Etiology, PathogenesisTop

Cholera is a highly contagious bacterial infection of the gastrointestinal (GI) tract.

1. Etiologic agent: Vibrio cholerae; ~200 serogroups have been identified, but only 2 of them bear epidemic potential: O1 (classical and El Tor biotypes) and O139. Each biotype from the O1 serogroup has 3 serotypes: Ogawa, Inaba, and Hikojima.

2. Pathogenesis: V cholerae colonizes the small intestine, where it produces a toxin causing secretory diarrhea. Cholera toxin is a hexamer made up of an enzymatically active A subunit and 5 B subunits that bind to gangliosides—receptors located on the surface of the enterocyte membrane. The A subunit penetrates epithelial cells in the small intestine mucosa and activates adenylate cyclase. It inhibits absorption of sodium ions and activates secretion of chloride ion. Subsequent osmotic flow of molecules results in penetration of water and then of ions of sodium, potassium, and HCO3– in the intestinal lumen. This causes watery secretory diarrhea leading to profound dehydration and loss of electrolytes.

3. Reservoir and transmission: Humans and bacteria able to survive and multiply in water (mainly waters at river mouths contaminated with sewage) are reservoirs for V cholerae. The infection spreads through the fecal-oral route.

4. Risk factors: Sources of infection include water contaminated with human feces (groundwater, rivers, river deltas, freshwater reservoirs, coastal waters including sea waters) and certain foods such as raw or undercooked fish, crustaceans (crayfish, crabs, spiny lobsters, lobsters, shrimps), mollusks (snails, mussels, oysters), and marine plants (algae).

Vulnerability to infection is increased in persons receiving medications that reduce HCl secretion in the stomach (proton pump inhibitors or H2 blockers) or neutralize HCl. Individuals with a history of gastrectomy, vagotomy, achlorhydria, and those with blood group 0 are particularly prone to infection and severe disease. Infection via direct contact with an infected person or carrier is rare.

5. Incubation and contagious period: The incubation period ranges from >10 hours to 5 days. Asymptomatic carriers can excrete V cholerae with feces for several weeks to months.

EpidemiologyTop

Cholera spreads mainly in regions with limited access to treated drinking water and nonoptimal sanitary conditions. The exact number of cases in individual countries cannot be established due to inadequate diagnostic evaluation and underreporting (according to the World Health Organization [WHO], only 5%-10% of all cases of cholera are officially reported every year).

The WHO estimates the incidence of cholera at 1.3 to 4 million cases per year, and mortality at 21,000 to 143,000 deaths annually. Cholera may occur as an endemic or epidemic disease (endemic areas are regions where cases of cholera with confirmed local transmission of V cholerae were detected within past 3 years). Endemic areas are located mainly in Africa, Asia, and Oceania.

Clinical Features and Natural HistoryTop

In individuals infected with V cholerae, fever and abdominal pain are absent. The disease typically manifests with watery diarrhea without mucus or blood, with a bland, fishy odor. Stool has the appearance of water in which rice has been washed (“rice-water” stool). Patients do not feel the urge to defecate and stools are passed without the possibility of stopping. Vomiting is a frequent manifestation. The abdomen is soft and nonpainful. Muscle cramps do not increase the patient’s body temperature. Dehydration develops quickly, particularly in children, the elderly, and those with comorbidities. Excretion of large amounts of bicarbonates, sodium, and potassium with feces results in metabolic acidosis. Hypokalemia leads to life-threatening arrhythmias, muscle cramps, and muscle weakness. Patients with choleric diarrhea are apathetic, and with time become highly exhausted and unable to go to the toilet on their own. Severity of dehydration depending on weight loss: see Diarrhea.

The WHO estimates that ~75% of infected individuals are asymptomatic but excrete V cholerae with feces, which subsequently contaminates the surrounding environment. In 80% of symptomatic patients the clinical image is the same as in traveler’s diarrhea or other mild GI tract infections; therefore, differential diagnosis cannot be established without bacteriologic testing.

DiagnosisTop

Diagnostic Tests

1. Identification of the etiologic agent:

1) Culture using selective media: Identification of V cholerae, its serogroup and serotype with biochemical tests and monoclonal antibodies.

2) Microscopic stool examination: Motile V cholerae are observed on dark-field microscopy of a fresh, liquid specimen; no neutrophils or erythrocytes are seen upon direct examination.

3) Identification of V cholerae toxin or lipopolysaccharides of O1 and O139 serogroups in stool using immunological methods.

4) Serologic examination: Detection of specific antibodies against V cholerae toxin or antigens.

2. Other: Laboratory tests indicating dehydration, electrolyte imbalance, and metabolic acidosis.

Diagnostic Criteria

1. Clinical criteria: Watery diarrhea is a characteristic manifestation.

2. Laboratory criteria: Identification of toxigenic O1 or O139 serogroups of V cholerae in stool or vomits; detection of specific antibodies against V cholerae toxin or antigens.

3. Probable diagnosis: Characteristic clinical features that match with epidemiologic data.

4. Confirmed diagnosis: Characteristic clinical features and laboratory-confirmed infection.

Differential Diagnosis

Traveler’s diarrhea, other infections and parasite invasions of the GI tract.

TreatmentTop

Antimicrobial Treatment

1. First-line agents: Oral tetracycline 500 mg every 6 hours for 3 days or oral doxycycline 300 mg in a single dose, or oral azithromycin 500 mg every 24 hours for 3 days.

2. Second-line agents: Oral ciprofloxacin 1 g in a single dose or oral erythromycin 250 mg every 8 hours for 3 days.

Symptomatic Treatment

Intensive oral rehydration therapy, IV if necessary: see Diarrhea.

ComplicationsTop

Acute kidney injury, arrhythmia, hypovolemic shock, coma.

PrognosisTop

Prognosis is uncertain for voluminous diarrhea, particularly in small children and the elderly with chronic diseases. It depends on access to IV rehydration and possibility of rapid correction of water–electrolyte and acid–base imbalances.

PreventionTop

Specific Prevention

Immunoprophylaxis: see Vaccines: Cholera.

Nonspecific Prevention

1. Following basic hygiene precautions, drinking water that has been boiled or treated in another way, and eating safe foods (thermally processed).

2. Quarantine: As required by local regulations; in some countries a 5-day quarantine is mandatory for contacts of persons with confirmed or suspected V cholerae infection.

3. Isolation: Patient isolation is required; local regulations may apply. Precautions for direct contact transmission should be taken.

4. Personal protective equipment (PPE) should be used, particularly by the personnel taking care of patients with confirmed or suspected V cholerae infection.