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Adult cholera patient.jpg
A person with severe dehydration due to cholera causing sunken eyes and wrinkled hands and skin.
SpecialtyInfectious disease
SymptomsLarge amounts of watery diarrhea, vomiting, muscle cramps[1][2]
ComplicationsDehydration, electrolyte imbalance[1]
Usual onset2 hours to 5 days after exposure[2]
DurationFew days[1]
CausesVibrio cholerae spread by fecal-oral route[1][3]
Risk factorsPoor sanitation, not enough clean drinking water, poverty[1]
Diagnostic methodStool test[1]
PreventionImproved sanitation, clean water, cholera vaccines[1][4]
TreatmentOral rehydration therapy, zinc supplementation, intravenous fluids, antibiotics[1][5]
Frequency3–5 million people a year[1]
Deaths28,800 (2015)[6]

Cholera is an infection of the small intestine by some strains of the bacterium Vibrio cholerae.[3][2] Symptoms may range from none, to mild, to severe.[2] The classic symptom is large amounts of watery diarrhea that lasts a few days.[1] Vomiting and muscle cramps may also occur.[2] Diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance.[1] This may result in sunken eyes, cold skin, decreased skin elasticity, and wrinkling of the hands and feet.[4] Dehydration can cause the skin to turn bluish.[7] Symptoms start two hours to five days after exposure.[2]

Cholera is caused by a number of types of Vibrio cholerae, with some types producing more severe disease than others.[1] It is spread mostly by unsafe water and unsafe food that has been contaminated with human feces containing the bacteria.[1] Undercooked seafood is a common source.[8] Humans are the only animal affected.[1] Risk factors for the disease include poor sanitation, not enough clean drinking water, and poverty.[1] There are concerns that rising sea levels will increase rates of disease.[1] Cholera can be diagnosed by a stool test.[1] A rapid dipstick test is available but is not as accurate.[9]

Prevention methods against cholera include improved sanitation and access to clean water.[4] Cholera vaccines that are given by mouth provide reasonable protection for about six months.[1] They have the added benefit of protecting against another type of diarrhea caused by E. coli.[1] The primary treatment is oral rehydration therapy—the replacement of fluids with slightly sweet and salty solutions.[1] Rice-based solutions are preferred.[1] Zinc supplementation is useful in children.[5] In severe cases, intravenous fluids, such as Ringer's lactate, may be required, and antibiotics may be beneficial.[1] Testing to see which antibiotic the cholera is susceptible to can help guide the choice.[2]

Cholera affects an estimated 3–5 million people worldwide and causes 28,800–130,000 deaths a year.[1][6] Although it is classified as a pandemic as of 2010, it is rare in the developed world.[1] Children are mostly affected.[1][10] Cholera occurs as both outbreaks and chronically in certain areas.[1] Areas with an ongoing risk of disease include Africa and Southeast Asia.[1] The risk of death among those affected is usually less than 5% but may be as high as 50%.[1] No access to treatment results in a higher death rate.[1] Descriptions of cholera are found as early as the 5th century BC in Sanskrit.[4] The study of cholera in England by John Snow between 1849 and 1854 led to significant advances in the field of epidemiology.[4][11] Seven large outbreaks have occurred over the last 200 years with millions of deaths.[12]

Video summary (script)

Signs and symptoms

Typical cholera diarrhea that looks like "rice water".

The primary symptoms of cholera are profuse diarrhea and vomiting of clear fluid.[13] These symptoms usually start suddenly, half a day to five days after ingestion of the bacteria.[14] The diarrhea is frequently described as "rice water" in nature and may have a fishy odor.[13] An untreated person with cholera may produce 10 to 20 litres (3 to 5 US gal) of diarrhea a day.[13] Severe cholera, without treatment, kills about half of affected individuals.[13] If the severe diarrhea is not treated, it can result in life-threatening dehydration and electrolyte imbalances.[13] Estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100.[15] Cholera has been nicknamed the "blue death"[16] because a person's skin may turn bluish-gray from extreme loss of fluids.[17]



Scanning electron microscope image of Vibrio cholerae
Vibrio cholerae, the bacterium that causes cholera.


Cholera has been found in two animal populations: shellfish and plankton.[13]

Transmission is usually through the fecal-oral route of contaminated food or water caused by poor sanitation.[1] Most cholera cases in developed countries are a result of transmission by food, while in the developing world it is more often water.[13] Food transmission can occur when people harvest seafood such as oysters in waters infected with sewage, as Vibrio cholerae accumulates in planktonic crustaceans and the oysters eat the zooplankton.[18]

People infected with cholera often have diarrhea, and disease transmission may occur if this highly liquid stool, colloquially referred to as "rice-water", contaminates water used by others.[19] A single diarrheal event can cause a one-million fold increase in numbers of V. cholerae in the environment.[20] The source of the contamination is typically other cholera sufferers when their untreated diarrheal discharge is allowed to get into waterways, groundwater or drinking water supplies. Drinking any contaminated water and eating any foods washed in the water, as well as shellfish living in the affected waterway, can cause a person to contract an infection. Cholera is rarely spread directly from person to person.[medical citation needed]

V. cholerae also exists outside the human body in natural water sources, either by itself or through interacting with phytoplankton, zooplankton, or biotic and abiotic detritus.[21] Drinking such water can also result in the disease, even without prior contamination through fecal matter. Selective pressures exist however in the aquatic environment that may reduce the virulence of V. cholerae.[21] Specifically, animal models indicate that the transcriptional profile of the pathogen changes as it prepares to enter an aquatic environment.[21] This transcriptional change results in a loss of ability of V. cholerae to be cultured on standard media, a phenotype referred to as 'viable but non-culturable' (VBNC) or more conservatively 'active but non-culturable' (ABNC).[21] One study indicates that the culturability of V. cholerae drops 90% within 24 hours of entering the water, and furthermore that this loss in culturability is associated with a loss in virulence.[21][22]



About 100 million bacteria must typically be ingested to cause cholera in a normal healthy adult.[13] This dose, however, is less in those with lowered gastric acidity (for instance those using proton pump inhibitors).[13] Children are also more susceptible, with two- to four-year-olds having the highest rates of infection.[13] Individuals' susceptibility to cholera is also affected by their blood type, with those with type O blood being the most susceptible.[13] Persons with lowered immunity, such as persons with AIDS or malnourished children, are more likely to experience a severe case if they become infected.[24] Any individual, even a healthy adult in middle age, can experience a severe case, and each person's case should be measured by the loss of fluids, preferably in consultation with a professional health care provider.[medical citation needed]

The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage: heterozygous carriers of the mutation (who are thus not affected by cystic fibrosis) are more resistant to V. cholerae infections.[25] In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the intestinal epithelium, thus reducing the effects of an infection.


The role of biofilm in the intestinal colonization of Vibrio cholerae.

When consumed, most bacteria do not survive the acidic conditions of the human stomach.[26] The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down protein production. When the surviving bacteria exit the stomach and reach the small intestine, they must propel themselves through the thick mucus that lines the small intestine to reach the intestinal walls where they can attach and thrive.[26]



Microbiologists have studied the genetic mechanisms by which the V. cholerae bacteria turn off the production of some proteins and turn on the production of other proteins as they respond to the series of chemical environments they encounter, passing through the stomach, through the mucous layer of the small intestine, and on to the intestinal wall.[28] Of particular interest have been the genetic mechanisms by which cholera bacteria turn on the protein production of the toxins that interact with host cell mechanisms to 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 unless an appropriate mixture of dilute salt water and sugar is taken to replace the blood's water and salts lost in the diarrhea.[medical citation needed]


Genetic structure


Antibiotic resistance

In many areas of the world, antibiotic resistance is increasing within cholera bacteria. In Bangladesh, for example, most cases are resistant to tetracycline, trimethoprim-sulfamethoxazole, and erythromycin.[30] Rapid diagnostic assay methods are available for the identification of multi-drug resistant cases.[31] New generation antimicrobials have been discovered which are effective against cholera bacteria in in vitro studies.[32]


A rapid dipstick test is available to determine the presence of V. cholerae.[30] In those samples that test positive, further testing should be done to determine antibiotic resistance.[30] In epidemic situations, a clinical diagnosis may be made by taking a patient history and doing a brief examination. Treatment is usually started without or before confirmation by laboratory analysis.




Preventive inoculation against cholera in 1966.

The World Health Organization (WHO) recommends focusing on prevention, preparedness, and response to combat the spread of cholera.[34] They also stress the importance of an effective surveillance system.[34] Governments can play a role in all of these areas.

Although cholera may be life-threatening, prevention of the disease is normally straightforward if proper sanitation practices are followed. In developed countries, due to nearly universal advanced water treatment and sanitation practices present there, cholera is rare. For example, the last major outbreak of cholera in the United States occurred in 1910–1911.[35][36] Cholera is mainly a risk in developing countries.


  • Sterilization: Proper disposal and treatment of all materials that may have come into contact with cholera victims' feces (e.g., clothing, bedding, etc.) are essential. These should be sanitized by washing in hot water, using chlorine bleach if possible. Hands that touch cholera patients or their clothing, bedding, etc., should be thoroughly cleaned and disinfected with chlorinated water or other effective antimicrobial agents.
  • Sewage and fecal sludge management: In cholera-affected areas, sewage and fecal sludge need to be treated and managed carefully in order to stop the spread of this disease via human excreta. Provision of sanitation and hygiene is an important preventative measure.[34] Open defecation, release of untreated sewage, or dumping of fecal sludge from pit latrines or septic tanks into the environment need to be prevented.[37] In many cholera affected zones, there is a low degree of sewage treatment.[38][39] Therefore, the implementation of dry toilets that do not contribute to water pollution, as they do not flush with water, may be an interesting alternative to flush toilets.[40]
  • Water purification: All water used for drinking, washing, or cooking should be sterilized by either boiling, chlorination, ozone water treatment, ultraviolet light sterilization (e.g., by solar water disinfection), or antimicrobial filtration in any area where cholera may be present. Chlorination and boiling are often the least expensive and most effective means of halting transmission. Cloth filters or sari filtration, though very basic, have significantly reduced the occurrence of cholera when used in poor villages in Bangladesh that rely on untreated surface water. Better antimicrobial filters, like those present in advanced individual water treatment hiking kits, are most effective. Public health education and adherence to appropriate sanitation practices are of primary importance to help prevent and control transmission of cholera and other diseases.






Euvichol-plus oral vaccine for cholera

A number of safe and effective oral vaccines for cholera are available.[43] The World Health Organization (WHO) has three prequalified oral cholera vaccines (OCVs): Dukoral, Sanchol, and Euvichol. Dukoral, an orally administered, inactivated whole cell vaccine, has an overall efficacy of about 52% during the first year after being given and 62% in the second year, with minimal side effects.[43] It is available in over 60 countries. However, it is not currently[when?] recommended by the Centers for Disease Control and Prevention (CDC) for most people traveling from the United States to endemic countries.[44] The vaccine that the US Food and Drug Administration (FDA) recommends, Vaxchora, is an oral attenuated live vaccine, that is effective as a single dose.[45]

One injectable vaccine was found to be effective for two to three years. The protective efficacy was 28% lower in children less than five years old.[46] However, as of 2010, it has limited availability.[1] Work is under way to investigate the role of mass vaccination.[47] The WHO recommends immunization of high-risk groups, such as children and people with HIV, in countries where this disease is endemic.[1] If people are immunized broadly, herd immunity results, with a decrease in the amount of contamination in the environment.[30]

Sari filtration

An effective and relatively cheap method to prevent the transmission of cholera is the use of a folded sari (a long cloth garment) to filter drinking water.[48] In Bangladesh this practice was found to decrease rates of cholera by nearly half.[49] It involves folding a sari four to eight times.[48] Between uses the cloth should be rinsed in clean water and dried in the sun to kill any bacteria on it.[50] A nylon cloth appears to work as well but is not as affordable.[49]


Cholera patient being treated by oral rehydration therapy in 1992.

Continued eating speeds the recovery of normal intestinal function. The WHO recommends this generally for cases of diarrhea no matter what the underlying cause.[51] A CDC training manual specifically for cholera states: "Continue to breastfeed your baby if the baby has watery diarrhea, even when traveling to get treatment. Adults and older children should continue to eat frequently."[52]


The most common error in caring for patients with cholera is to underestimate the speed and volume of fluids required.[53] In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is highly effective, safe, and simple to administer.[30] Rice-based solutions are preferred to glucose-based ones due to greater efficiency.[30] In severe cases with significant dehydration, intravenous rehydration may be necessary. Ringer's lactate is the preferred solution, often with added potassium.[13][51] Large volumes and continued replacement until diarrhea has subsided may be needed.[13] Ten percent of a person's body weight in fluid may need to be given in the first two to four hours.[13] This method was first tried on a mass scale during the Bangladesh Liberation War, and was found to have much success.[54] Despite widespread beliefs, fruit juices and commercial fizzy drinks like cola, are not ideal for rehydration of people with serious infections of the intestines, and their excessive sugar content may even harm water uptake.[55]



As there frequently is initially acidosis, the potassium level may be normal, even though large losses have occurred.[13] As the dehydration is corrected, potassium levels may decrease rapidly, and thus need to be replaced.[13] This may be done by consuming foods high in potassium, like bananas or coconut water.[57]


Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms.[13] Use of antibiotics also reduces fluid requirements.[58] People will recover without them, however, if sufficient hydration is maintained.[30] The WHO only recommends antibiotics in those with severe dehydration.[57]

Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance.[13] Testing for resistance during an outbreak can help determine appropriate future choices.[13] Other antibiotics proven to be effective include cotrimoxazole, erythromycin, tetracycline, chloramphenicol, and furazolidone.[59] Fluoroquinolones, such as ciprofloxacin, also may be used, but resistance has been reported.[60]

Antibiotics improve outcomes in those who are both severely and not severely dehydrated.[61] Azithromycin and tetracycline may work better than doxycycline or ciprofloxacin.[61]

Zinc supplementation

In Bangladesh zinc supplementation reduced the duration and severity of diarrhea in children with cholera when given with antibiotics and rehydration therapy as needed. It reduced the length of disease by eight hours and the amount of diarrhea stool by 10%.[62] Supplementation appears to be also effective in both treating and preventing infectious diarrhea due to other causes among children in the developing world.[62][63]





Cholera affects an estimated 3–5 million people worldwide, and causes 58,000–130,000 deaths a year as of 2010.[1][66] This occurs mainly in the developing world.[67] In the early 1980s, death rates are believed to have been greater than three million a year.[13] 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.[30] Cholera remains[when?] both epidemic and endemic in many areas of the world.[13] In October 2016, an outbreak of cholera began in war-ravaged Yemen.[68] WHO called it "the worst cholera outbreak in the world".[69]




The word cholera is from Greek: χολέρα kholera from χολή kholē "bile". Cholera likely has its origins in the Indian subcontinent as evidenced by its prevalence in the region for centuries.[13] Early outbreaks in the Indian subcontinent are believed to have been the result of poor living conditions as well as the presence of pools of still water, both of which provide ideal conditions for cholera to thrive.[71] The disease first spread by trade routes (land and sea) to Russia in 1817, later to the rest of Europe, and from Europe to North America and the rest of the world.[13] Seven cholera pandemics have occurred in the past 200 years, with the seventh pandemic originating in Indonesia in 1961.[72]

The first cholera pandemic occurred in the Bengal region of India, near Calcutta starting in 1817 through 1824. The disease dispersed from India to Southeast Asia, the Middle East, Europe, and Eastern Africa.[73] The movement of British Army and Navy ships and personnel is believed to have contributed to the range of the pandemic, since the ships carried people with the disease to the shores of the Indian Ocean, from Africa to Indonesia, and north to China and Japan.[74] The second pandemic lasted from 1826 to 1837 and particularly affected North America and Europe due to the result of advancements in transportation and global trade, and increased human migration, including soldiers.[75] The third pandemic erupted in 1846, persisted until 1860, extended to North Africa, and reached South America, for the first time specifically affecting Brazil. The fourth pandemic lasted from 1863 to 1875 spread from India to Naples and Spain. The fifth pandemic was from 1881–1896 and started in India and spread to Europe, Asia, and South America. The sixth pandemic started 1899–1923. These epidemics were less fatal due to a greater understanding of the cholera bacteria. Egypt, the Arabian peninsula, Persia, India, and the Philippines were hit hardest during these epidemics, while other areas, like Germany in 1892 and Naples from 1910–1911, also experienced severe outbreaks. The seventh pandemic originated in 1961 in Indonesia and is marked by the emergence of a new strain, nicknamed El Tor, which still persists (as of 2018[76]) in developing countries.[77]

Since it became widespread in the 19th century, cholera has killed tens of millions of people.[78] In Russia alone, between 1847 and 1851, more than one million people perished of the disease.[79] It killed 150,000 Americans during the second pandemic.[80] Between 1900 and 1920, perhaps eight million people died of cholera in India.[81] Cholera became the first reportable disease in the United States due to the significant effects it had on health.[13] John Snow, in England, was the first to identify the importance of contaminated water as its cause in 1854.[13] Cholera is now no longer considered a pressing health threat in Europe and North America due to filtering and chlorination of water supplies, but still heavily affects populations in developing countries.

In the past, vessels flew a yellow quarantine flag if any crew members or passengers were suffering from cholera. No one aboard a vessel flying a yellow flag would be allowed ashore for an extended period, typically 30 to 40 days.[82] In modern[when?] sets of international maritime signal flags, the quarantine flag is yellow and black.

Historically many different claimed remedies have existed in folklore. Many of the older remedies were based on the miasma theory. Some believed that abdominal chilling made one more susceptible and flannel and cholera belts were routine in army kits.[83] In the 1854–1855 outbreak in Naples homeopathic camphor was used according to Hahnemann.[84] T. J. Ritter's "Mother's Remedies" book lists tomato syrup as a home remedy from northern America. Elecampane was recommended in the United Kingdom according to William Thomas Fernie.[85]

Cholera cases are much less frequent in developed countries where governments have helped to establish water sanitation practices and effective medical treatments.[86] The United States, for example, used to[when?] have a severe cholera problem similar to those in some developing countries. There were three large cholera outbreaks in the 1800s, which can be attributed to Vibrio cholerae's spread through interior waterways like the Erie Canal and routes along the Eastern Seaboard.[87] The island of Manhattan in New York City touched the Atlantic Ocean, where cholera collected just off the coast. At this time, New York City did not have as effective a sanitation system as it does today,[when?] so cholera was able to spread.[88]

Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically cholera.[89]


How to avoid the cholera leaflet; Aberystwyth; August 1849.

The bacterium was isolated in 1854 by Italian anatomist Filippo Pacini,[90] but its exact nature and his results were not widely known.


Russian-Jewish bacteriologist Waldemar Haffkine developed the first cholera vaccine in July 1892.[92]

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.[71] Dr. Snow proposed a microbial origin for epidemic cholera in 1849. In his major "state of the art" review of 1855, he proposed a substantially complete and correct model for the cause of the disease. In two pioneering epidemiological field studies, he was able to demonstrate human sewage contamination was the most probable disease vector in two major epidemics in London in 1854.[93] His model was not immediately accepted, but it was seen to be the more plausible, as medical microbiology developed over the next 30 years or so.


Robert Allan Phillips, working at the US Naval Medical Research Unit Two in Southeast Asia, evaluated the pathophysiology of the disease using modern laboratory chemistry techniques and developed a protocol for rehydration. His research led the Lasker Foundation to award him its prize in 1967.[95]


Society and culture

Health policy

In many developing countries, cholera still reaches its victims through contaminated water sources, and countries without proper sanitation techniques have greater incidence of the disease.[97] Governments can play a role in this. In 2008, for example, the Zimbabwean cholera outbreak was due partly to the government's role, according to a report from the James Baker Institute.[18] The Haitian government's inability to provide safe drinking water after the 2010 earthquake led to an increase in cholera cases as well.[98]



According to Colwell, the quality and inclusiveness of a country's health care system affects the control of cholera, as it did in the Zimbabwean cholera outbreak.[18] While sanitation practices are important, when governments respond quickly and have readily available vaccines, the country will have a lower cholera death toll. Affordability of vaccines can be a problem; if the governments do not provide vaccinations, only the wealthy may be able to afford them and there will be a greater toll on the country's poor.[102][103] The speed with which government leaders respond to cholera outbreaks is important.[104]


Notable cases


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