eMedicine Specialties > Infectious Diseases > Gastrointestinal Tract and Intra-abdominal Infections
Cholera
Updated: Nov 20, 2007
Introduction
Background
The word cholera is derived from a Greek term that means "flow of bile." Cholera is caused by Vibrio cholerae, the most feared epidemic diarrheal disease because of its severity. Dehydration and death can occur within hours of infection.
Robert Koch discovered V cholerae in 1883 during an outbreak in Egypt. The organism is a comma-shaped, gram-negative aerobic bacillus whose size varies from 1-3 µm in length by 0.5-0.8 µm in diameter. Its antigenic structure consists of a flagellar H antigen and a somatic O antigen. The differentiation of the latter allows for separation into pathogenic and nonpathogenic strains. V cholerae O1 and V cholerae O139 are associated with epidemic cholera. V cholerae O1 is classified into 2 major biotypes: classic and El Tor. Currently, El Tor is the predominant cholera pathogen. Organisms in both biotypes are subdivided into serotypes according to the structure of the O antigen, as follows:
- Serotype Inaba - O antigens A and C
- Serotype Ogawa - O antigens A and B
- Serotype Hikojima - O antigens A, B, and C
Pathophysiology
The infectious dose of bacteria required to cause clinical disease varies by the mode of administration. If ingested with water, the infectious dose is 103 -106 organisms. When ingested with food, fewer organisms (102 -104 organisms) are required to produce disease.
The use of antacids, histamine receptor blockers, and proton pump inhibitors increases the risk of cholera infection and predisposes patients to more severe disease as a result of reduced gastric acidity. The same applies to patients with chronic gastritis secondary to Helicobacter pylori infection or those who have undergone a gastrectomy.
V cholerae O1 and V cholerae O139 cause clinical disease by producing an enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of the small intestine. The enterotoxin is a protein molecule composed of 5 B subunits and 2 A subunits. The B subunits are responsible for binding to a ganglioside (monosialosyl ganglioside, GM1) receptor located on the surface of the cells that line the intestinal mucosa.
The activation of the A1 subunit by adenylate cyclase is responsible for the net increase in cyclic adenosine monophosphate (cAMP). cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells. The result is watery diarrhea with electrolyte concentrations isotonic to those of plasma.
Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected. The colon is usually in a state of absorption because it is relatively insensitive to the toxin. However, the large volume of fluid produced in the upper intestine overwhelms the absorptive capacity of the lower bowel, resulting in severe diarrhea.
The enterotoxin acts locally and does not invade the intestinal wall. As a result, few neutrophils are found in the stool.
Frequency
United States
Among the millions of Americans who travel to endemic areas in foreign countries, only 42 imported cases of cholera were reported from 1965-1991. However, in August 1986, 4 cases of cholera were acquired in Louisiana and 1 case was acquired in Florida. These patients were hospitalized with severe diarrhea and had stool cultures that yielded toxigenic V cholerae O1 Inaba. Although the vehicle of transmission was not specifically identified, the patients had consumed seafood within 5 days prior to symptom onset. Toxigenic V cholerae O1 El Tor Inaba appears to have an environmental reservoir on the US Gulf Coast.
Sixty-one cases of cholera were reported from January 1, 1995, through December 31, 2000, in 18 states and 2 US territories. Thirty-seven were travel-associated cases; the other 24 cases were acquired in the United States.1 Individuals living in the United States most often acquire cholera through travel to cholera-endemic areas or through consumption of undercooked seafood from the Gulf Coast or foreign waters.
In 2005, 12 cases were reported to the World Health Organization (WHO) and, of these, 8 were imported.
International
Since 1817, 7 cholera pandemics have occurred. The first 6 occurred from 1817-1923 and were probably the result of V cholerae O1 of the classic biotype. The pandemics originated in Asia, with subsequent spread to Europe and the Americas.
The seventh pandemic was caused by V cholerae O1 El Tor, which was first isolated in Egypt in 1905. The pandemic originated from the CelebesIslands, Indonesia, in 1961; this pandemic affected more countries and continents than the previous 6 pandemics. The last extension of this pandemic was into Latin America. The total number of cases officially reported from 1997 through March 26, 1998, was 120,867; 89% of these cases were reported in Africa.
In 2002, all regions of the world continued to report cholera caused by V cholerae O1 El Tor; that year, 142,311 cases and 4564 deaths were reported to the WHO by 52 countries. Compared with 2001, the number of reported cases almost doubled.
Between 2002 and 2004, the number of cases reported to the WHO decreased worldwide. In 2005, however, the number reported increased 30% to a total of 131,943 cases in 52 countries.
In October 1992, an epidemic of cholera emerged from Madras, India, as a result of a new serogroup, O139 (also known as Bengal). This Bengal strain has now spread throughout Bangladesh and India and into neighboring countries in Asia. Some experts regard this as an eighth pandemic. Thus far, 11 countries in Southeast Asia have reported isolation of this Vibrio serogroup.
Mortality/Morbidity
If untreated, the disease rapidly results in dehydration and can result in death in more than 50% of infected individuals. The mortality rate is increased in pregnant women and children.
Age
People of all ages are susceptible, although infants are protected through maternally transmitted antibodies during breastfeeding. An attack of the classic biotype of V cholerae usually protects against recurrent infection by either biotype, but El Tor cholera does not protect against further attacks.
Clinical
History
After a 24- to 48-hour incubation period, symptoms begin with the sudden onset of painless watery diarrhea that may quickly become voluminous and is often followed by vomiting. The patient may experience accompanying abdominal cramps. Fever is typically absent. The diarrhea has a "rice water" appearance and a fishy odor. In patients with severe disease, the stool volume can exceed 250 mL/kg in the first 24 hours. Without replacement of fluids and electrolytes, hypovolemic shock and death ensue.
Physical
Clinical signs of cholera parallel the level of volume contraction. The amount of fluid loss and the corresponding clinical signs of cholera are as follows:
- With 3-5% loss of normal body weight - Excessive thirst
- With 5-8% loss of normal body weight - Postural hypotension, tachycardia, weakness, fatigue, and dry mucous membranes or dry mouth
- With greater than 10% loss of normal body weight - Oliguria; glassy or sunken eyes; sunken fontanelles in infants; weak, thready, or absent pulse; wrinkled "washerwoman" skin; somnolence; and coma
- Pediatric patients
- In pediatric patients, the primary signs are similar to those in adults.
- Children with severe cholera may present with signs that are rarely seen in adults. A child with cholera is usually very drowsy, and coma is not uncommon.
- In addition, pediatric patients may have convulsions that appear to be related, in part, to hypoglycemia because patients exhibit some response to intravenous dextrose.
- Another significant difference from the adult presentation is that children are often febrile.
Causes
- Cholera is transmitted via the fecal-oral route. Owing to the relatively large infectious dose, transmission occurs almost exclusively via contaminated water or food. Toxigenic V cholerae O1 has been shown to survive in crabs boiled for 8 minutes, but not in crabs boiled for 10 minutes. Transmission via direct person-to-person contact is rare.
- V cholerae is unable to survive in an acidic environment. Therefore, any condition that reduces gastric acid production increases the risk of acquisition. In addition, although the pathophysiology is not understood, individuals with blood group O are at increased risk of developing El Tor cholera.
More on Cholera |
 Overview: Cholera |
| Differential Diagnoses & Workup: Cholera |
| Treatment & Medication: Cholera |
| Follow-up: Cholera |
| References |
| Next Page » |
References
Steinberg EB, Greene KD, Bopp CA, Cameron DN, Wells JG, Mintz ED. Cholera in the United States, 1995-2000: trends at the end of the twentieth century. J Infect Dis. Sep 15 2001;184(6):799-802. [Medline].
Centers for Disease Control and Prevention. Toxigenic Vibrio cholerae 01 infections--Louisiana and Florida. MMWR Morb Mortal Wkly Rep. Sep 26 1986;35(38):606-7. [Medline].
Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 6th ed. Philadelphia, Pa: Churchill Livingstone; 2004.
Seas C, DuPont HL, Valdez LM, Gotuzzo E. Practical guidelines for the treatment of cholera. Drugs. Jun 1996;51(6):966-73. [Medline].
Thompson RF, Bass DM, Hoffman SL. Travel vaccines. Infect Dis Clin North Am. Mar 1999;13(1):149-67, vii. [Medline].
Woodruff AW. A Synopsis of Infectious and Tropical Diseases. 3rd ed. Bristol, England: Wright; 1987:186-90.
Further Reading
Keywords
cholera, Vibrio cholerae, V cholerae, V cholerae El Tor, V cholerae O1, V cholerae O139, diarrhea, diarrheal diseases, dehydration, El Tor, Inaba, Ogawa, Hikojima, Bengal, gram-negative bacteria, bacterial infection, bacteremia, water-borne bacteria, water contamination, fecal contamination, enterotoxin, undercooked seafood, pandemic, fecal-oral contamination, fecal oral contamination, oral rehydration solution, ORS, water treatment, sewage disposal
