Cholera is an acute infection of the small bowel by Vibrio cholerae, which secretes a toxin that causes copious watery diarrhea, leading to dehydration, oliguria, and circulatory collapse. Infection is typically through contaminated water or seafood. Diagnosis is by culture or serology. Treatment is vigorous rehydration and electrolyte replacement plus doxycycline.
The causative organism, V. cholerae, serogroups 01 and 0139, is a short, curved, motile, aerobic bacillus that produces enterotoxin, a protein that induces hypersecretion of an isotonic electrolyte solution by the small-bowel mucosa. Both the El Tor and classic biotypes of V. cholerae can cause severe disease. However, mild or asymptomatic infection is much more common with the El Tor biotype.
Cholera is spread by ingestion of water, seafood, or other foods contaminated by the excrement of people with symptomatic or asymptomatic infection. Cholera is endemic in portions of Asia, the Middle East, Africa, South and Central America, and the Gulf Coast of the US. Cases transported into Europe, Japan, and Australia have caused localized outbreaks. In endemic areas, outbreaks usually occur during warm months. The incidence is highest in children. 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 vibrios (see Gram-Negative Bacilli: Noncholera Vibrio Infections).
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. People living in endemic areas gradually acquire a natural immunity.
Symptoms and Signs
The incubation period 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/h but is usually much less. 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 K+ depletion (but normal serum Na+ concentration) occur. If cholera is untreated, circulatory collapse with cyanosis and stupor may follow. Prolonged hypovolemia can cause renal tubular necrosis.
Most patients are free of V. cholerae within 2 wk after cessation of diarrhea; chronic biliary tract carriers are rare.
Diagnosis is confirmed by stool culture and subsequent serotyping. Cholera can be distinguished from clinically similar disease caused by enterotoxin-producing strains of Escherichia coli and occasionally by Salmonella and Shigella. Serum electrolytes, BUN, and creatinine should be measured.
Replacement of fluid loss is essential. Mild cases can be treated with standard oral replacement formulas (see Dehydration and Fluid Therapy in Children: Oral Rehydration). 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 (for details on fluid resuscitation, see Shock and Fluid Resuscitation: Intravenous Fluid Resuscitation and see Dehydration and Fluid Therapy in Children: Oral Rehydration). Water should also be given freely by mouth. To replace K+ losses, KCl 10 to 15 mEq/L can be added to the IV solution, or KHCO3 1 mL/kg po of a 100-g/L solution can be given qid. K+ replacement is especially important for children, who tolerate hypokalemia poorly.
Once intravascular volume is restored, amounts for replacement of continuing losses should equal measured stool volume. 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 h). Those with more severe dehydration need more and may need to receive the fluid by nasogastric tube. The oral solution recommended by the WHO contains 20 g glucose, 3.5 g NaCl, 2.9 g trisodium citrate and dihydrate (or 2.5 g NaHCO3), and 1.5 g KCl per liter of drinking water. This solution should be continued ad libitum after rehydration in amounts at least equal to continuing stool and vomitus losses. Solid food should be given only after vomiting stops and appetite returns.
Early treatment with an effective oral antimicrobial eradicates vibrios, reduces stool volume by 50%, and stops diarrhea within 48 h. The choice of antimicrobial should be based on the susceptibility of V. cholerae isolated from the community.
Drugs effective for susceptible strains include
For control of cholera, human excrement must be correctly disposed of, and water supplies purified. In endemic regions, drinking water should be boiled or chlorinated, and vegetables and fish cooked thoroughly.
A killed oral whole cell-B subunit vaccine (not available in the US) provides 85% protection against the 01 serogroup for 4 to 6 mo. Protection lasts up to 3 yr in adults but wanes rapidly in children and is greater for the classic than for the El Tor biotype. There is no cross-protection between 01 and 0139 serogroups. Vaccines proven effective against both serogroups are a future goal. The parenteral cholera vaccine is not recommended because of its low efficacy, short duration (43% for 3 mo), and frequent severe adverse effects.
Prompt prophylaxis with doxycycline 100 mg po q 12 h in adults (TMP/SMX can be used for prophylaxis in children < 9 yr) can decrease secondary cases among household contacts of cholera patients, but mass prophylaxis is inappropriate and some strains are not sensitive.
Noncholera Vibrio Infections
Noncholera vibrios include Vibrio parahaemolyticus, V. mimicus, V. alginolyticus, V. hollisae, and V. vulnificus; these vibrios are sometimes called nonagglutinable vibrios (ie, they do not agglutinate with serum from cholera patients). They typically inhabit warm salt water or mixed salt and fresh water (eg, in estuaries).
V. parahaemolyticus, V. mimicus, and V. hollisae usually cause food-borne outbreaks of diarrhea, typically involving inadequately cooked seafood (usually shellfish). V. parahaemolyticus infections typically occur in Japan and in coastal areas of the US. The organisms damage intestinal mucosa but do not produce enterotoxin or invade the bloodstream. Also, wound infection may develop when contaminated warm seawater enters a minor wound.
V. alginolyticus and V. vulnificus can cause serious wound infection; neither causes enteritis. V. vulnificus, when ingested by a compromised host (often someone with chronic liver disease or immunodeficiency), can cross the intestinal mucosa without causing enteritis and cause septicemia with a high mortality rate; occasionally, otherwise healthy people develop such infections.
Symptoms and Signs
After a 15- to 24-h incubation period, enteric illness begins suddenly with cramping abdominal pain, large amounts of watery diarrhea (stools may be bloody and contain PMNs), tenesmus, weakness, and sometimes nausea, vomiting, and low-grade fever. Symptoms subside spontaneously in 24 to 48 h.
Cellulitis can rapidly develop in contaminated wounds in some cases (typically those involving V. vulnificus) and progress to necrotizing fasciitis with typical hemorrhagic, bullous lesions.
V. vulnificus septicemia causes shock, bullous skin lesions, and often manifestations of disseminated intravascular coagulation (eg, thrombocytopenia, hemorrhage); mortality rate is high.
Wound and bloodstream infections are readily diagnosed with routine cultures. When enteric infection is suspected, Vibrio organisms can be cultured from stool on thiosulfate citrate bile salts sucrose medium. Contaminated seafood also yields positive cultures.
Noncholera Vibrio enteric infections can be treated with a single dose of ciprofloxacin 1 g po or doxycycline 300 mg po. For diarrhea, close attention to volume repletion and replacement of lost electrolytes are needed.
For wound infections, antibiotics are used—typically, doxycycline 100 mg po q 12 h, with or without a 3rd-generation cephalosporin for severe wound infection or septicemia. Patients with necrotizing fasciitis require surgical debridement.
Last full review/revision August 2009 by Burke A. Cunha, MD
Content last modified February 2012