Cholera, Vibrio cholerae

Cholera is a potentially epidemic and life-threatening secretory diarrhea characterized by numerous, voluminous watery stools, often accompanied by vomiting, and resulting in hypovolemic shock and acidosis. It is caused by certain members of the species Vibrio cholerae which can also cause mild or inapparent infections. Other members of the species may occasionally cause isolated outbreaks of milder diarrhea whereas othersthe vast majorityare free-living and not associated with disease.

Vibrios are Gram-negative, highly motile curved rods with a single polar flagellum. They tolerate alkaline media that kill most intestinal commensals, but they are sensitive to acid. Numerous free-living vibrios are known, some potentially pathogenic. Until 1992, cholera was caused by only two serotypes, Inaba (AC) and Ogawa (AB), and two biotypes, classical and El Tor, of toxigenic O group 1 V cholerae. These organisms may be identified by agglutination in O group 1-specific antiserum directed against the lipopolysaccharide component of the cell wall and by demonstration of their enterotoxigenicity. In 1992, cholera caused by serogroup O139 (synonym "Bengal" the 139th and latest serogroup of V cholerae to be identified) emerged in epidemic proportions in India and Bangladesh. This serovar is identified by 1) absence of agglutination in O group 1 specific antiserum; 2) by agglutination in O group 139 specific antiserum; and 3) by the presence of a capsule.

Cholera is transmitted by the fecal-oral route. Vibrios are sensitive to acid, and most die in the stomach. Surviving virulent organisms may adhere to and colonize the small bowel, where they secrete the potent cholera enterotoxin (CT, also called "choleragen"). This toxin binds to the plasma membrane of intestinal epithelial cells and releases an enzymatically active subunit that causes a rise in cyclic adenosine 5¹-monophosphate (cAMP) production. The resulting high intracellular cAMP level causes massive secretion of electrolytes and water into the intestinal lumen.

Gastric acid, mucus secretion, and intestinal motility are the prime nonspecific defenses against V cholerae. Breastfeeding in endemic areas is important in protecting infants from disease. Disease results in effective specific immunity, involving primarily secretory immunoglobulin (IgA), as well as IgG antibodies, against vibrios, somatic antigen, outer membrane protein, and/or the enterotoxin and other products.

Cholera is endemic or epidemic in areas with poor sanitation; it occurs sporadically or as limited outbreaks in developed countries. In coastal regions it may persist in shellfish and plankton. Long-term convalescent carriers are rare. Enteritis caused by the halophile V parahaemolyticus is associated with raw or improperly cooked seafood.

The diagnosis is suggested by strikingly severe, watery diarrhea. For rapid diagnosis, a wet mount of liquid stool is examined microscopically. The characteristic motility of vibrios is stopped by specific antisomatic antibody. Other methods are culture of stool or rectal swab samples on TCBS agar and other selective and nonselective media; the slide agglutination test of colonies with specific antiserum; fermentation tests (oxidase positive); and enrichment in peptone broth followed by fluorescent antibody tests, culture, or retrospective serologic diagnosis. More recently the polymerase chain reaction (PCR) and additional genetically-based rapid techniques have been recommended for use in specialized laboratories.

Control by sanitation is effective but not feasible in endemic areas. A good vaccine has not yet been developed. A parenteral vaccine of whole killed bacteria has been used widely, but is relatively ineffective and is not generally recommended. An experimental oral vaccine of killed whole cells and toxin B-subunit protein is less than ideal. Living attenuated genetically engineered mutants are promising, but such strains can cause limited diarrhea as a side effect. Antibiotic prophylaxis is feasible for small groups over short periods.

Other serogroups of V cholerae may cause diarrheal disease and other infections but are not associated with epidemic cholera. Vibrio parahaemolyticus is an important cause of enteritis associated with the ingestion of raw or improperly prepared seafood. Other Vibrio species, including V vulnificus, can cause infections of humans and other animals including fish. Campylobacter species (formerly included with vibrios) can cause enteritis. C pylori, now known as Helicobacter pylori, is associated with gastric and duodenal ulcers