Cholera overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Tarek Nafee, M.D. [2], Aysha Anwar, M.B.B.S[3], Sara Mehrsefat, M.D. [4], Priyamvada Singh, MBBS [5]

Cholera is an infection of the small intestine caused by the bacterium Vibrio cholerae. The main symptoms are profuse, watery diarrhea and vomiting. Transmission occurs primarily by drinking water or eating food that has been contaminated by the feces of an infected person, including one with no apparent symptoms. The severity of the associated diarrhea and vomiting can lead to rapid dehydration, an electrolyte imbalance, and, in some cases, death. The primary treatment is oral rehydration therapy, typically with oral rehydration solution (ORS), which serves to replace water and electrolytes. If this is not tolerated or does not provide fast enough improvement, intravenous fluids can also be used. Antibacterial drugs are beneficial in those with severe forms of the disease, as they shorten the duration and mitigate the severity of cholera. Worldwide, cholera affects 3–5 million people and causes 100,000–130,000 deaths a year. Cholera was one of the earliest infections to be studied with epidemiological methods.

The cholera-causing bacterium was originally isolated in 1855 by Italian anatomist Filippo Pacini, but its exact nature and his results were not widely known. One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist John Snow (1813–1858), who, in 1854, identified a link between cholera and contaminated drinking water.^[1] Dr. Snow proposed a microbial origin for epidemic cholera in 1849.

Most of the V. cholerae bacteria cannot survive the highly acidic conditions of the human stomach.^[2] The few bacteria that do manage to survive the stomach's acidity conserve their energy and stored nutrients during passage through the stomach by largely shutting down protein production and subsequently restarting production in the more favorable environment of the small intestine. The toxins that interact with mechanisms of the host cell pump chloride ions into the small intestine, creating an ionic pressure that prevents sodium ions from entering the cell. The chloride and sodium ions create a saltwater environment in the small intestine, which, through osmosis, can pull up to six liters of water per day through the intestinal cells. This effect is responsible for the high frequency of diarrhea that is characteristic of cholera. The host can rapidly become severely dehydrated if an appropriate mixture of dilute saltwater and sugar is not taken to replace the blood's water and salts lost in the diarrhea.

Vibrio cholerae is a gram negative bacterium with a curved-rod shape that causes cholera in humans.^[3] V. cholerae and other species of the genus Vibrio belong to the gamma subdivision of the Proteobacteria.  There are two major strains of V. cholerae, classic and El Tor, and numerous other serogroups.^{[3][4][5][6][7]}

Patients with cholera may have a history of consumption of contaminated food or water and travel to an endemic area. The symptoms usually develop within 24-48 hours of consumption of contaminated food. Patients present with sudden-onset, painless, odorless, rice-watery, large volume stool; abdominal cramps; vomiting; and fever. It should be differentiated from other infectious causes of diarrhea (e.g., rotavirus, E. coli, amoebic dysentry, giardiasis). It should also be differentiated from some non-infectious causes of diarrhea (e.g., VIPoma, tubulovillous adenoma, food poisoning).^{[8][9][10][11]}

Cholera affects an estimated 3-5 million people worldwide and causes 100,000-130,000 deaths a year as of 2010. Mortality due to cholera occurs mainly in the developing world.^[12] In the early 1980s, death rates are believed to have been greater than 3 million a year. It is difficult to calculate exact numbers of cases, as many go unreported due to concerns that an outbreak may have a negative impact on the tourism industries of endemic countries.^[13] Cholera remains both epidemic and endemic in many areas of the world. Although much is known about the mechanisms behind the spread of cholera, this has not led to a full understanding of what makes cholera outbreaks happen in some places but not others. Inadequate or nonexistent treatment of human feces and drinking water greatly facilitate the spread of cholera, while bodies of water can serve as reservoirs and seafood shipped over long distances can spread the disease. Cholera was not observed in the Americas for most of the 20th century, but it reappeared towards the end of that century and seems likely to persist.^[14]

Certain factors have been found to be associated with an increased risks of cholera. Among these are decreased immunity, decreased gastric pH, certain blood groups (people with type O blood are most prone, while people with type AB blood are least prone), and genetics are the most commonly associated factors.^[15][16][17] At particular risk are people residing in over-populated communities and refugee settings characterized by poor sanitation, unsafe drinking water, and, consequently, increased person-to-person transmission.^[18]

There are no screening guidelines for cholera.^[19]

Cholera infection can cause a severe diarrheal illness through the acute and substantial loss of water and electrolytes.^[3] The incubation period is very short (between 2 hours and 5 days); consequently, the number of cases in an area can rise extremely quickly. Delayed initiation of oral rehydration therapy or inadequate rehydration may lead to hypotension and electrolyte imbalance (mostly hypokalemia). Untreated dehydration may lead to hypotension, which can result in renal failure, hypovolemic shock, coma, and death. Untreated hypokalemia can lead to nephropathy and focal myocardial necrosis. Among children, hypoglycemia is common and can lead to seizures.^[18] If a patient with cholera is treated quickly and properly, the mortality rate is less than 1%. Without adequate treatment, the mortality rate rises to 50–60%.^[20][21]

A cholera patient's history may involve the consumption of contaminated food or water and/or travel to an endemic area. Symptoms associated with cholera usually develop within 24-48 hour of infection. Patients present with sudden-onset, painless, odorless, rice-watery, large-volume stool; abdominal cramps; vomiting; and fever. If the severe diarrhea and vomiting are not aggressively treated, they can result in life-threatening dehydration and electrolyte imbalances within hours. The typical symptoms of dehydration include dizziness (due to low blood pressure), wrinkled hands (due to poor skin turgor), sunken eyes, muscle cramps (due to hypokalemia), and decreased urine output.^[8][22][23]

Signs of cholera on a physical examination depend on the patient's level of dehydration. The patient may present with tachycardia, postural hypotension, somnolence, dry mucous membrane, sunken eyes, and/or oliguria. If the severe diarrhea and vomiting are not aggressively treated, they can result in life-threatening dehydration and electrolyte imbalances within hours. Typical symptoms of dehydration include dizziness (due to low blood pressure), wrinkled hands (due to poor skin turgor), sunken eyes, muscle cramps (due to hypokalemia), and decreased urine output.

Laboratory tests are not mandatory for the diagnosis and treatment of cholera. When cholera is suspected in an endemic area, treatment should be started as early as possible with fluid replacement and antibiotics. In areas where cholera is uncommon, it is worthwhile to perform lab tests. Tests used for the identification of organisms include direct microscopic examination of organism, dark field examination, gram staining, culture, antigen, polymerase chain reaction, and serotype tests.^{[24][25][26][27][28][29][5]}

There are no x-ray findings associated with cholera infection.^[24][25]

There are no CT scan findings associated with cholera infection.^[24][25]

There are no MRI findings associated with cholera infection.^[24][25][30]

Other diagnostic tests which may be used for cholera toxin detection include (EIS) microfluidic chips for flow immunoassay and lab-on-a-bubble surface enhanced raman indirect immunoassay for cholera.^[31][32]

In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is highly effective, safe, and simple to administer. In severe cases with significant dehydration, intravenous rehydration may be necessary. Ringer's lactate is the preferred solution, often with added potassium. Large volumes and continued replacement may be necessary until diarrhea has subsided.^[33][34] Ten percent of a person's body weight in fluid may need to be given in the first two to four hours. Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms.^[35] Patients can recover even without antibiotics, as long as sufficient hydration and electrolyte balance is maintained. Doxycycline is typically used as a first-line intervention,^[36] although some strains of V. cholerae have shown resistance.^[37] Zinc supplementation has been shown to reduce stool output and to reduce the duration and severity of symptoms.^[38]

Surgery is not recommended for the management of cholera.

Primary prevention of cholera can be achieved on an individual level by appropriate personal hygiene; use of sanitary water supply; appropriate preparation of food; as well as prompt identification, isolation, and treatment of new cases. Primary preventive methods may also be implemented on a community level through effective water sanitation, appropriate, and broad vaccination of the community to develop herd immunity, as well as early detection of an outbreak.^{[39][40][41][42][43][44]}

Secondary prevention of cholera includes prompt and appropriate diagnosis and treatment of patients with suspected cholera.^[33][34]

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