Cholera

Patricia Cristofaro, M.D.
Glenn G. Fort, M.D., M.P.H.

Basic Information

Definition

Cholera is an acute diarrheal illness caused by toxin-producing strains of Vibrio cholerae.

ICD-10CM CODES
A00.0	Cholera due to Vibrio cholerae 01, biovar cholerae
A00.1	Cholera due to Vibrio cholerae 01, biovar eltor
A00.9	Cholera, unspecified

Epidemiology & Demographics

Incidence (In U.S.)

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Extremely rare. Less than 25 cases have been reported in the United States since 2012.
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Cholera is endemic in 60 countries. In the world, ∼2.9 million cases and 100,000 deaths occur annually.

Peak Incidence

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None in the U.S.
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Summer and fall in endemic areas (Africa, South and Southeast Asia)

Predominant Sex

None

Predominant Age

In nonendemic areas, attack rates are equal in all age groups. In epidemic areas, children older than the age of 2 yr are most commonly infected. Neonatal infection: illness is uncommon before the age of 2 yr, likely because of passive immunity.

Physical Findings & Clinical Presentation

Infection may result in asymptomatic illness or a mild diarrhea. The classic illness is described as the abrupt onset of voluminous watery diarrhea, which may lead to severe dehydration, acidosis, shock, and death. Vomiting may occur early in the illness, but fever and abdominal pain are usually absent. The typical “rice water” stools are pale with flecks of mucus and contain no blood. Muscle cramps may be prominent and are the result of loss of fluid and electrolytes. Untreated illness results in hypovolemic shock, and death may occur in hours to days. With adequate fluid and electrolyte repletion, cholera is a self-limited illness that resolves in a few days. The use of antimicrobials can shorten the course of illness.

Etiology

The organism responsible for this illness is one of several strains of V. cholerae. Most infections result from the O1 serotype, the El Tor biotype. In the U.S., one outbreak occurred from the ingestion of illegally imported crab, and sporadic infection has been associated with the consumption of contaminated shellfish in Gulf Coast states. Most cases are seen in returning travelers. Transmission during epidemics is the result of the ingestion of contaminated water and, in some instances, contaminated food.

An important outbreak of cholera followed the 2010 earthquake in Haiti, with many cases also in the Dominican Republic (which shares the island of Hispaniola with Haiti). Subsequently, cholera was detected in Cuba, Venezuela, and Florida in travelers from Hispaniola. Interestingly, the strain of cholera was related to the strains of Southeast Asia rather than South America and was possibly introduced by UN peacekeepers from Nepal.

Diagnosis

Differential Diagnosis

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Mild illness may mimic gastroenteritis resulting from a variety of etiologies.
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Sudden, voluminous diarrhea causing marked dehydration is uncommon in other illnesses.

Workup

Stool should be sent for culture and microscopy. Treatment should not be delayed while awaiting culture results.

Laboratory Tests

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WBC may be elevated, and hemoglobin may be increased as a result of hemoconcentration.
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Elevated BUN and creatinine suggests prerenal azotemia. Hypoglycemia may occur. Stool cultures on appropriate media may grow the organism. Wet mount of stool under dark field or phase contrast microscopy shows organisms with characteristic darting motility.

Treatment

Nonpharmacologic Therapy

The mainstay of therapy is adequate fluid and electrolyte replacement (Table E1). This can usually be achieved using oral rehydration solutions containing salts and glucose. Some patients may require intravenous fluid and electrolyte replacement.

TABLEE1 Electrolyte Concentration of Cholera Stools and Common Solutions Used for TreatmentFrom Mandell GL et al: Principles and practice of infectious diseases, ed 6, Philadelphia, 2005, Churchill Livingstone.

	Electrolyte and Glucose Concentration (mmol/L)
	Na⁺	Cl⁻	K⁺	HCO₃⁻	Glucose
Cholera stool
Adults	130	100	20	44
Children	100	90	33	30
Intravenous solutions
Ringer’s lactate	130	109	4	28^∗	0
Dhaka	133	98	13	48	0
Normal saline	154	154	0	0	0
Peru polyelectrolyte	90	80	20	30	111
WHO ORS	90	80	20	30^†	111
WHO ORS, World Health Organization oral rehydration solution.

Acute General Rx

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Antimicrobial therapy can decrease shedding of fluid and organisms and can shorten the course of illness:
1. 1.
  
  Doxycycline 300 mg PO single dose or
2. 2.
  
  Azithromycin two 500-mg tablets PO as a single dose or
3. 3.
  
  Tetracycline 500 mg PO qid × 3 days or
4. 4.
  
  Erythromycin 500 mg qid × 3 days
5. 5.
  
  Ciprofloxacin 1 g as a single dose
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For pregnant women: azithromycin 1 g PO single dose.
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For children: azithromycin 20 mg/kg PO as a single dose.
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Resistance to SMX-TMP is increasing in travel-associated infections, so SMX-TMP is no longer recommended.
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Zinc and vitamin A supplementation may be helpful in children.
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Susceptibility testing is often available to tailor the choice of antibiotic.

Chronic Rx

It is likely that asymptomatic chronic carriers exist; however, because they are difficult to identify and their role in transmission of disease appears to be rather limited, there is no recommendation for treatment of these individuals.

Disposition

The mortality rate of adequately hydrated patients is less than 1%.

Referral

If more than mild illness occurs

Reporting

In the U.S., all cases of cholera must be reported to the local and state health departments. Bacterial isolates must be sent to the state health department and the CDC.

Prevention

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A killed oral cholera vaccine (Stanchol) has been available for prevention of cholera outside the U.S. It is administered in a two-dose schedule. However, a recent trial revealed that a single dose of Stanchol was efficacious in older children (<greater than or equal to symbol>5 years of age) and in adults in a setting with a high level of cholera endemicity.^{<ce:sup>1</ce:sup>}
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In 2016 the FDA approved Vaxchora (PaxVax, Inc., Redwood City, CA), a single-dose, oral, live-attenuated cholera vaccine, for protection against <ce:italic>Vibrio cholerae</ce:italic> serogroup 01 in adults 18 to 64 years old traveling to endemic or epidemic areas who are at high risk of exposure. The vaccine is administered as a single dose at least 10 days before potential exposure. Cost for one dose is $200 to $250. The vaccine should not be given to patients who have taken oral or parenteral antibiotics in the previous two weeks.

Pearls & Considerations

Comments

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Vaccination now recommended.
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Recent guidelines from the Advisory Committee for Immunization Practices (ACIP) were published in the May 12, 2017, Morbidity and Mortality Weekly Report (MMWR).
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Lyophilized CVD 103-HgR is now recommended for adults (ages 18-64) traveling to areas with endemic or epidemic cholera caused by <ce:italic>V. cholerae</ce:italic> O1.
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Brand name is Vaxchora.

Summary of Findings

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This is the only vaccine licensed for use in the U.S.
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This is a LIVE, oral, single-dose vaccine.
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Efficacy against severe diarrhea is 90% at 10 days after vaccination, falling to 80% at 3 mo.
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No serious adverse events have been reported.
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The vaccine strain may be shed in the stool for 7 days or more.
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The vaccine is not routinely recommended for travelers who are not visiting areas of active cholera transmission.
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No data currently exists on the safety and effectiveness of lyophilized CVD 103-HgR vaccine in children and teens aged <18 years or adults aged ≥65 years and use of vaccine in immunocompromised persons and pregnant and breastfeeding women.

Ferri – Cholera