Cholera (ORPHA:173)
Cholera is an infectious disease, caused by intestinal infection with Vibrio cholerae, characterized by massive watery diarrhea and severe dehydration that can lead to shock and death if left untreated.
Epidemiology
Cholera is endemic to over 50 countries (defined as having reported cholera cases for the last 3 years with evidence of local transmission), mainly in Asia and Africa. In addition, outbreaks have occurred throughout Africa, Asia, the Middle East, South and Central America, and the Caribbean. Worldwide, it is estimated that there are 1-4 million cases per year. In Europe, the disease is extremely rare, occurring as isolated, imported cases.
Clinical description
Once ingested, the incubation period ranges from 12 hours to 5 days. The majority of infected individuals will be asymptomatic, a smaller percentage will develop mild to moderate symptoms, and only a small proportion will develop severe dehydration. Cholera afflicts children and adults equally during epidemics among immunologically-naive populations but in endemic populations, children are more affected. Onset of severe cholera begins with profuse watery diarrhea with a ''rice water'' appearance, usually accompanied by vomiting. Some may experience abdominal cramping and discomfort but fever is extremely rare. Signs of dehydration and electrolyte imbalance soon occur and include sunken eyes, lethargy, dry mouth, decreased skin turgor, wrinkled hands and feet, and cold clammy skin. Kussmaul breathing and muscle cramping are seen in some. In children, seizures, altered consciousness, and coma can occur due to severe hypoglycemia. If left untreated, cholera can lead to severe dehydration, shock, and death within hours.
Etiology
Cholera is due to an infection with Vibrio cholerae, a Gram negative rod bacteria that grows best in coastal waters and estuaries and is spread by the fecal-oral route. Over 200 serogroups exist but only 2 cause epidemic cholera: O1 and O139. The O1 serogroup is additionally subdivided into the Ogawa and Inaba serotypes. Once ingested, V. cholerae colonizes the small intestine where it releases cholera toxin that results in secretory diarrhea. The disease is associated with poor sanitation resources and lack of access to adequate water.
Diagnostic methods
Diagnosis is based on the sudden onset of severe diarrhea as well as recent exposure to the bacteria.  V. cholerae can be isolated from stool samples on selective media, followed by biochemical tests along with serogrouping and serotyping. The comma-shaped, motile bacteria can also be identified by examining fresh stool under dark field microscopy. Immunoassays that detect cholera toxins or  V. cholerae O1 and O139 lipopolysaccharides in the stool are also available.
Differential diagnosis
Mild cases can be confused with other causes of gastroenteritis such as Escherichia coli and rotavirus infections.
Management and treatment
Treatment involves immediate rehydration with oral rehydration solutions (preferred when possible) containing salt and glucose or rice-based rehydration solutions and/or isotonic intravenous (IV) solutions. Individuals with severe cholera require an average of 200 ml/kg of fluids within the first 24 hours (may need >350 ml/kg). The initial fluid deficit should be replaced within 3-4 hours of presentation. Antibiotics such as tetracyclines, fluoroquinolones and macrolides are beneficial in moderate to severe cases and should be chosen based on availability and local resistance patterns. A high energy diet should be established once dehydration has been corrected to prevent malnutrition and complications. Access to safe drinking water and adequate sanitation prevents the spread of cholera. Two oral killed cholera vaccines are available, WC-rBS (whole-cell/recombinant B-subunit oral cholera vaccine; licensed in the EU) and BivWC (bivalent whole-cell oral cholera vaccine; used in endemic settings), which are given as 2 or 3 doses and provide 60-85% protection for 2-3 years. Children less than 5 years old, however, receive less protection from vaccination and for a shorter duration than adults.
Prognosis
With proper treatment, the prognosis is good with a mortality rate of <0.2%. If untreated, the mortality rate can reach 50-70%.

                            Last update: 
                            September 2019


                            - Expert reviewer(s): 
                            Dr Alaina RITTER