Cholera is an acute infection of the small bowel caused by the gram-negative bacterium Vibrio cholerae. V. cholerae
The causative organism, V. cholerae, is a short, curved, motile, aerobic, gram-negative bacillus that produces enterotoxin, a protein that induces hypersecretion of an isotonic electrolyte solution by the small-bowel mucosa. Humans are the only known natural host for V. cholerae. After penetrating the mucus layer, V. cholerae colonize the epithelial lining of the gut and secrete cholera toxin. These organisms do not invade the intestinal wall; thus, few or no white blood cells are found in stool.
Cholera epidemics are caused only by V. cholerae serogroups O1 and O139. Both the El Tor and classic biotypes of V. cholerae O1 can cause severe disease. However, mild or asymptomatic infection is much more common with the currently predominant El Tor biotype and with non-O1 and non-O139 serogroups of V. cholerae.
Cholera is spread by ingestion of water, shellfish, or other foods contaminated by the excrement of people with symptomatic or asymptomatic infection. Household contacts of patients with cholera are at high risk of infection, which probably occurs through shared sources of contaminated food and water. Person-to-person transmission is less likely to occur because a large inoculum of organism is needed to transmit the infection.
Cholera is endemic in portions of Asia, the Middle East, Africa, South and Central America, and the Gulf Coast of the United States. In 2010, an outbreak started in Haiti and lasted until 2017. It later spread to the Dominican Republic and Cuba. During this outbreak, over 820,000 people became ill, and nearly 10,000 died. Cases transported into Europe, Japan, and Australia caused localized outbreaks. An outbreak in Yemen started in 2016 and has not yet ended. This outbreak has had even greater devastating effects. Over 2.5 million people in Yemen have become ill, and almost 4,000 have died. It is thought to be the largest, fastest-spreading cholera outbreak in modern history, and, at its peak in 2019, accounted for over 90% of cholera cases in the world. Haiti also had a new outbreak that started at the end of 2022 after the country had been declared cholera-free for 3 years (1). It is still ongoing.
Cholera outbreaks have increased globally since 2021, and WHO-reported cases doubled from 2021 to 2022. Seven countries in Africa and Asia reported outbreaks with > 10,000 cases each in 2022 (2, 3).
In endemic areas, outbreaks usually occur during warm months. The incidence is highest in children, young and/or undernourished children in particular. In newly affected areas, epidemics may occur during any season, and all ages are equally susceptible.
A milder form of gastroenteritis is caused by noncholera V. cholerae serogroups O1 and O139, which do not produce cholera toxin.
Susceptibility to infection varies and is greater for people with blood type O. Because vibrios are sensitive to gastric acid, hypochlorhydria and achlorhydria are predisposing factors, including in patients taking gastric acid–suppressing medications.
People living in endemic areas gradually acquire a natural immunity.
References
1. Vega Ocasio D, Juin S, Berendes D, et al. Cholera Outbreak - Haiti, September 2022-January 2023. MMWR Morb Mortal Wkly Rep. 2023;72(2):21-25. Published 2023 Jan 13. doi:10.15585/mmwr.mm7202a1
2. Larkin H. WHO Report: Cholera Resurgent in 2022 After Years of Decline. JAMA. 2023;329(3):200. doi:10.1001/jama.2022.23551
3. World Health Organization = Organisation mondiale de la Santé: Weekly Epidemiological Record, 2023, vol. 98, 38 [full issue]. Weekly Epidemiological Record = Relevé épidémiologique hebdomadaire, 98 (38), 431-452.
Symptoms and Signs of Cholera
The incubation period for cholera is 1 to 3 days. Cholera can be subclinical, a mild and uncomplicated episode of diarrhea, or a fulminant, potentially lethal disease.
Abrupt, painless, watery diarrhea and vomiting are usually the initial symptoms. Significant nausea is typically absent. Stool loss in adults may exceed 1 L/hour but is usually much less. Often, stools consist of white liquid void of fecal material (rice-water stool).
The resultant severe water and electrolyte depletion leads to intense thirst, oliguria, muscle cramps, weakness, and marked loss of tissue turgor, with sunken eyes and wrinkling of skin on the fingers. Hypovolemia, hemoconcentration, oliguria and anuria, and severe metabolic acidosis with potassium depletion (but normal serum sodium concentration) occur. If cholera is untreated, circulatory collapse with cyanosis and stupor may follow. Prolonged hypovolemia can cause acute tubular necrosis.
Untreated cholera causes death in > 50% of people, but with timely rehydration, death occurs in approximately 1% of people (1).
Most patients are free of V. cholerae within 2 weeks after cessation of diarrhea; chronic biliary tract carriers are rare.
Symptoms and signs reference
1. Fournier JM, Quilici ML. Choléra [Cholera]. Presse Med. 2007;36(4 Pt 2):727-739. doi:10.1016/j.lpm.2006.11.029
Diagnosis of Cholera
Stool culture and serogrouping/subtyping
Diagnosis of cholera is confirmed by stool culture (use of selective media is recommended) plus subsequent serogrouping/subtyping.
Tests for V. cholerae are available in reference laboratories; polymerase chain reaction (PCR) testing is also an option. Rapid dipstick testing for cholera is available for public health use in areas with limited access to laboratory testing, but specificity of this test is suboptimal, so dipstick-positive specimens should be confirmed by culture if possible.
Cholera should be distinguished from clinically similar disease caused by enterotoxin-producing strains of Escherichia coli and occasionally by Salmonella and Shigella.
Serum electrolytes, blood urea nitrogen, and creatinine should be measured.
Treatment of Cholera
Fluid replacement
Fluid replacement
Replacement of fluid loss is essential. Mild cases can be treated with standard oral rehydration formulas. Rapid correction of severe hypovolemia is lifesaving. Prevention or correction of metabolic acidosis and hypokalemia is important. For hypovolemic and severely dehydrated patients, IV replacement with isotonic fluids should be used (see oral rehydration). Water should also be given freely by mouth.
Once intravascular volume is restored (rehydration phase), amounts for replacement of continuing losses should equal measured stool volume (maintenance phase). Adequacy of hydration is confirmed by frequent clinical evaluation (pulse rate and strength, skin turgor, urine output). Plasma, plasma volume expanders, and vasopressors should not be used in place of water and electrolytes.
Oral glucose-electrolyte solution is effective in replacing stool losses and may be used after initial IV rehydration, and it may be the only means of rehydration in epidemic areas where supplies of parenteral fluids are limited. Patients who have mild or moderate dehydration and who can drink may be rehydrated with the oral solution (about 75 mL/kg in 4 hours). Those with more severe dehydration need more and may need to receive the fluid by nasogastric tube.
Using such prepared ORS packets minimizes the possibility of error when untrained people mix the solution. If ORS packets are not available, a reasonable substitute can be made by mixing half a small spoon of salt and 6 small spoons of sugar in 1 L of clean water. The ORS should be continued ad libitum after rehydration in amounts at least equal to continuing stool and vomitus losses.
Pearls & Pitfalls
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Solid food should be given only after vomiting stops and appetite returns.
Antimicrobials
Early treatment with an effective oral antimicrobial eradicates vibrios, reduces stool volume by 50%, and usually stops diarrhea within 48 hours. The choice of antimicrobial should be based on the susceptibility of V. cholerae isolated from the community (1).
doxycyclineRecommendations for the Use of Antibiotics for the Treatment of Cholera).
Recommended oral dosing (see also the CDC's recommendations) for susceptible strains include
Zinc supplementation has reduced the severity and duration of disease in children in low-resource areas of the world (2).
Treatment references
1. Leibovici-Weissman Y, Neuberger A, Bitterman R, Sinclair D, Salam MA, Paul M. Antimicrobial drugs for treating cholera. Cochrane Database Syst Rev. 2014;2014(6):CD008625. Published 2014 Jun 19. doi:10.1002/14651858.CD008625.pub2
2. Roy SK, Hossain MJ, Khatun W, et al. Zinc supplementation in children with cholera in Bangladesh: randomised controlled trial. BMJ. 2008;336(7638):266-268. doi:10.1136/bmj.39416.646250.AE
Prevention of Cholera
For control of cholera, human excrement must be correctly disposed of, and water supplies must be purified. In endemic regions, drinking water should be boiled or chlorinated, and vegetables and shellfish should be cooked thoroughly.
Antibiotic prophylaxis for household contacts of patients with cholera is not recommended because data supporting this measure are lacking. In addition, antibiotic resistance emerged in previous epidemics when antibiotic prophylaxis was given to household contacts of cholera patients.
Cholera vaccines
Several oral cholera vaccines are available.
V. cholerae CVD 103-HgR (Vaxchora), is available in the United States for people ages 2 to 64 years who are traveling to cholera-infected areas. It protects against disease caused by V. cholerae O1, reducing the chance of moderate and severe diarrhea by 90% at 10 days after vaccination and by 80% at 3 months after vaccination (1). The effectiveness of this vaccine beyond 3 to 6 months is unknown.
Three killed whole-cell oral vaccines are available for use in children and adults internationally but not in the United States:
A monovalent vaccine (travelers' diarrhea and cholera vaccine [Dukoral]) contains only V. cholera O1 and El Tor bacteria plus a small amount of nontoxic b subunit cholera toxin; before taking, it must be mixed into buffer fluid (buffer packet is dissolved in 150 mL [5 oz] of cool water).
Two bivalent vaccines (ShanChol and Euvichol) contain both O1 and O139 serogroups of V. cholera and have no added components, eliminating the requirement for fluid ingestion at the time of vaccination.
These 3 vaccines provide 60 to 85% protection for 2 to 3 years (2). They require 2 doses, and booster doses are recommended after 2 years for people with ongoing risk of cholera.
An injectable whole-cell parenteral vaccine formerly prepared from phenol-inactivated strains of V. cholerae is no longer in use because of its low efficacy and adverse effects.
Prevention references
1. Collins JP, Ryan ET, Wong KK, et alMMWR Recomm Rep. 2022;71(2):1-8. Published 2022 Sep 30. doi:10.15585/mmwr.rr7102a1
2. Song KR, Lim JK, Park SE, et alVaccines (Basel). 2021;9(12):1482. Published 2021 Dec 15. doi:10.3390/vaccines9121482
Key Points
V. cholerae serogroups O1 and O139 secrete an enterotoxin that can cause severe, sometimes fatal diarrheal illness that often occurs in large outbreaks caused by mass exposure to contaminated water or food.
Other V. cholerae serogroups can cause milder, nonepidemic disease.
Diagnose using stool culture and serotyping; a rapid dipstick test is helpful in identifying outbreaks in remote areas.
Rehydration is critical; oral rehydration solution is adequate for most cases, but patients with severe volume depletion require IV fluids.
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Centers for Disease Control and Prevention (CDC): Recommendations for the Use of Antibiotics for the Treatment of Cholera
