Cholera overview


 * Associate Editors-In-Chief: Priyamvada Singh, MBBS [mailto:psingh@perfuse.org]

Overview
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 diarrhea and vomiting can lead to rapid dehydration and electrolyte imbalance, and death in some cases. The primary treatment is oral rehydration therapy, typically with oral rehydration solution (ORS), to replace water and electrolytes. If this is not tolerated or does not provide improvement fast enough, intravenous fluids can also be used. Antibacterial drugs are beneficial in those with severe disease to shorten its duration and severity. Worldwide, it affects 3–5 million people and causes 100,000–130,000 deaths a year. Cholera was one of the earliest infections to be studied by epidemiological methods.

Historical perspective
The cholera bacterium had been 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 found a link between cholera and contaminated drinking water. Dr. Snow proposed a microbial origin for epidemic cholera in 1849.

Pathophysiology
Most of the V. cholerae bacteria do not survive the very acidic conditions of the human stomach. The few bacteria that manage to survive the stomach's acidity conserve their energy and stored nutrients during passage through the stomach by shutting down much protein production and restart production in the favorable small intestine's environment. The toxins that interact with host cell mechanisms pump chloride ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The chloride and sodium ions create a salt water environment in the small intestines which through osmosis can pull up to six liters of water per day through the intestinal cells creating the massive amounts of diarrhea. The host can become rapidly dehydrated if an appropriate mixture of dilute salt water and sugar is not taken to replace the blood's water and salts lost in the diarrhea.

Epidemiology and demographics
Cholera affects an estimated 3-5 million people worldwide, and causes 100,000-130,000 deaths a year as of 2010. This occurs mainly in the developing world. 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 of a country. 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 some places and not others. Lack of treatment of human feces and lack of treatment of drinking water greatly facilitate its spread, but bodies of water can serve as a reservoir, and seafood shipped long distances can spread the disease. Cholera was not known in the Americas for most of the 20th century, but it reappeared towards the end of that century and seems likely to persist.

Risk factors
Certain factors have been found to be associated with an increased risks of Cholera. Among these decreased immunity, decreased gastric pH, certain blood groups (Blood group O are most prone, blood group AB is least prone), and genetics are the commonest associated.

Prognosis
If people with cholera are treated quickly and properly, the mortality rate is less than 1%; however, with untreated cholera, the mortality rate rises to 50–60%. For certain genetic strains of cholera, such as the one present during the 2010 epidemic in Haiti and the 2004 outbreak in India, death can occur within two hours of the first sign of symptoms.

Causes
Cholera is a severe diarrheal disease caused by the gram negative bacterium Vibrio cholerae. . Transmission to humans is by ingesting contaminated water or food. The major reservoir for cholera was long assumed to be humans, but some evidence suggests that it is the aquatic environment.

Differential diagnosis
It should be differentiated from other infectious causes of diarrhea for e.g. rotavirus, E.coli, amebic dysentry and giardiasis. It should also be differentiated from some non-infectious causes of diarrhea for e.g. VIPoma, tubulovillous adenoma and food poisoning.

History and symptoms
Patient may give a history of consumption of contaminated food or water, and travel to an endemic area. The symptoms usually develop within 24-48 hour of consumption of contaminated food. Patient presents 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, within hours, result in life-threatening dehydration and electrolyte imbalances. The typical symptoms of dehydration include dizziness ( due to low blood pressure), wrinkled hands (poor skin turgor), sunken eyes, mucle cramps (decreased potassium), and decreased urine output.

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

Lab tests
Lab tests are not mandatory for diagnosis and treatment of cholera. In endemic areas when suspected, treatment should be started as early as possible with fluid replacement and antibiotics. In areas where cholera is uncommon, performing lab tests are worthwhile.Tests used for identification of organisms are: Direct microscopic examination of organism, dark field examination, gram staining, culture, antigen, polymerase chain reaction and serotype tests.

Medical therapy
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 until diarrhea has subsided may be needed. 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. People can recover even without them, if sufficient hydration and electrolyte balance is maintained. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance.

Primary prevention
Although cholera can be life-threatening, it is nearly always easily prevented, in principle, if proper sanitation practices are followed. In the United States and Western Europe, because of advanced water treatment and sanitation systems, cholera is no longer a major threat. The last major outbreak of cholera in the United States was in 1911. However, everyone, especially travelers, should be aware of how the disease is transmitted and what can be done to prevent it. Good sanitation practices, if instituted in time, are usually sufficient to stop an epidemic.