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Classification and external resources
Cholera is an infection of the small intestine caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission is primarily through consuming contaminated drinking water or food. The severity of the diarrhea and vomiting can lead to rapid dehydration and electrolyte imbalance. Primary treatment is with oral rehydration solution and if these are not tolerated, intravenous fluids. Antibiotics are beneficial in those with severe disease. Worldwide it affects 3-5 million people and causes 100,000-130,000 deaths a year as of 2010. Cholera was one of the earliest infections to be studied by epidemiological methods.
 Signs and symptoms
A person with severe dehydration due to cholera. Note the sunken eyes and decreased skin turgor which produces wrinkled handsThe primary symptoms of cholera are profuse painless diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, one to five days after ingestion of the bacteria. The diarrhea is frequently described as "rice water" in nature and may have a fishy odor. An untreated person with cholera may produce 10-20 liters of diarrhea a day. For every symptomatic person there are 3 to 100 people who get the infection but remain asymptomatic.
If the severe diarrhea and vomiting are not aggressively treated it can, within hours, result in dehydration and electrolyte imbalances. The typical symptoms of dehydration include: low blood pressure, poor skin turgor (wrinkled hands), sunken eyes, and a rapid pulse.
Main article: Vibrio cholerae
TEM image of Vibrio choleraeCholera is caused by the bacteria Vibrio cholerae mainly of the serogroup O1 but also possible of serogroup O139. Transmission is primarily due to the fecal contamination of food and water due to poor sanitation. This bacteria can however live naturally in aquatic environments.
About one hundred million bacteria must typically be ingested to cause cholera in a normal healthy adult. This dose however is less in those with lower gastric acidity ( from proton pump inhibitors etc. ). Children are also more susceptible with 2 to 4 year olds having the highest rates of infection.
It has been hypothesized that the cystic fibrosis genetic mutation has been maintained in humans due to a selective advantage: heterozygous carriers of the mutation (who are thus not affected by cystic fibrosis) are more resistant to V. cholerae infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the gastrointestinal epithelium, thus reducing the effects of an infection.
An individual's susceptibility to cholera is affected by their blood type with those with type O blood being the most susceptible.
Drawing of Death bringing the cholera, in Le Petit JournalCholera is typically transmitted by either contaminated food or water. In the developed world seafood is the usual cause while in the developing world it is more often water. Cholera has been found in only two other animal populations: shellfish and plankton.
People infected with cholera often have diarrhea and if this highly liquid stool, colloquially referred to as "rice-water," contaminates water used by others transmission may occur. The source of the contamination is typically other cholera sufferers when their untreated diarrhoea discharge is allowed to get into waterways or into groundwater or drinking water supplies. Any infected water and any foods washed in the water, as well as shellfish living in the affected waterway, can cause an infection. Cholera is rarely spread directly from person to person. Both toxic and non-toxic strains exist. Non-toxic strains can acquire toxicity through a lysogenic bacteriophage. Coastal cholera outbreaks typically follow zooplankton blooms, thus making cholera a zoonotic disease.
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Most bacteria when consumed do not survive the acidic conditions of the human stomach. The few bacteria that do survive conserve their energy and stored nutrients during the passage through the stomach by shutting down much protein production. When the surviving bacteria exit the stomach and reach the small intestine, they need to propel themselves through the thick mucus that lines the small intestine to get to the intestinal wall where they can thrive. V. cholerae bacteria start up production of the hollow cylindrical protein flagellin to make flagella, the curly whip-like tails that they rotate to propel themselves through the mucus of the small intestine.
Once the cholera bacteria reach the intestinal wall, they do not need the flagella propellers to move any longer. The bacteria stop producing the protein flagellin, thus again conserving energy and nutrients by changing the mix of proteins which they manufacture in response to the changed chemical surroundings. On reaching the intestinal wall, V. cholerae start producing the toxic proteins that give the infected person a watery diarrhea. This carries the multiplying new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place.
The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits: a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond. The five B subunits form a five-membered ring that binds to GM1 gangliosides on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins, while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis. Once inside the cell, the disulfide bond is reduced and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6). Binding exposes its active site, allowing it to permanently ribosylate the Gs alpha subunit of the heterotrimeric G protein. This results in constitutive cAMP production, which in turn leads to secretion of H2O, Na+, K+, Cl−, and HCO3− into the lumen of the small intestine and rapid dehydration. The gene encoding the cholera toxin is introduced into V. cholerae by horizontal gene transfer. Virulent strains of V. cholerae carry a variant of lysogenic bacteriophage called CTXf or CTXφ.
Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into cells. The toxic part (red) is activated inside the cell (PDB code: 1xtc).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. 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 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.
By inserting separate, successive sections of V. cholerae DNA into the DNA of other bacteria such as E. coli that would not naturally produce the protein toxins, researchers have investigated the mechanisms by which V. cholerae responds to the changing chemical environments of the stomach, mucous layers, and intestinal wall. Researchers have discovered that there is a complex cascade of regulatory proteins that control expression of V. cholerae virulence determinants. In responding to the chemical environment at the intestinal wall, the V. cholerae bacteria produce the TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of virulence genes that produce the toxins that cause diarrhea in the infected person and that permit the bacteria to colonize the intestine. Current research aims at discovering "the signal that makes the cholera bacteria stop swimming and start to colonize (that is, adhere to the cells of) the small intestine."
In epidemic situations, a clinical diagnosis may be made by taking a history and doing a brief examination. Treatment is usually started without or before confirmation by laboratory analysis.
A rapid dip-stick test is available to determine the presence of V. cholerae. In those that test positive further testing should be done to determine antibiotic resistance.
Stool and swab samples collected in the acute stage of the disease, before antibiotics have been administered, are the most useful specimens for laboratory diagnosis. If an epidemic of cholera is suspected, the most common causative agent is Vibrio cholerae O1. If V. cholerae serogroup O1 is not isolated, the laboratory should test for V. cholerae O139. However, if neither of these organisms is isolated, it is necessary to send stool specimens to a reference laboratory. Infection with V. cholerae O139 should be reported and handled in the same manner as that caused by V. cholerae O1. The associated diarrheal illness should be referred to as cholera and must be reported in the United States.
A number of special media have been employed for the cultivation for cholera vibrios. They are classified as follows:
 Enrichment media
Alkaline peptone water at pH 8.6
Monsur's taurocholate tellurite peptone water at pH 9.2
 Plating media
Alkaline bile salt agar (BSA): The colonies are very similar to those on nutrient agar.
Monsur's gelatin Tauro cholate trypticase tellurite agar (GTTA) medium: Cholera vibrios produce small translucent colonies with a greyish black centre.
TCBS medium: This the mostly widely used medium. This medium contains thiosulphate, citrate, bile salts and sucrose. Cholera vibrios produce flat 2–3 mm in diameter, yellow nucleated colonies.
Direct microscopy of stool is not recommended as it is unreliable. Microscopy is preferred only after enrichment, as this process reveals the characteristic motility of Vibrios and its inhibition by appropriate antiserum. Diagnosis can be confirmed as well as serotyping done by agglutination with specific sera.
Cholera hospital in Dhaka, showing typical cholera beds.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, cholera is no longer a major health threat. The last major outbreak of cholera in the United States occurred in 1910-1911. Effective sanitation practices, if instituted and adhered to in time, are usually sufficient to stop an epidemic. There are several points along the cholera transmission path at which its spread may be halted:
Sterilization: Proper disposal and treatment of infected faecal waste water produced by cholera victims and all contaminated materials (e.g. clothing, bedding, etc.) is essential. All materials that come in contact with cholera patients should be sterilized 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 anti-microbial agents.
Sewage: anti-bacterial treatment of general sewage by chlorine, ozone, ultra-violet light or other effective treatment before it enters the waterways or underground water supplies helps prevent undiagnosed patients from inadvertently spreading the disease.
Sources: Warnings about possible cholera contamination should be posted around contaminated water sources with directions on how to decontaminate the water (boiling, chlorination etc.) for possible use.
Water purification: All water used for drinking, washing, or cooking should be sterilized by either boiling, chlorination, ozone water treatment, ultra-violet light sterilization (e.g. by solar water disinfection), or anti-microbial 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, though very basic, have significantly reduced the occurrence of cholera when used in poor villages in Bangladesh that rely on untreated surface water. Better anti-microbial 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.
Surveillance and prompt reporting allow for containing cholera epidemics rapidly. Cholera exists as a seasonal disease in many endemic countries, occurring annually mostly during rainy seasons. Surveillance systems can provide early alerts to outbreaks, therefore leading to coordinated response and assist in preparation of preparedness plans. Efficient surveillance systems can also improve the risk assessment for potential cholera outbreaks. Understanding the seasonality and location of outbreaks provide guidance for improving cholera control activities for the most vulnerable. For prevention to be effective it is important that cases are reported to national health authorities.
A number of safe and effective oral vaccines for cholera are available. Dukoral an orally administered inactivated whole cell vaccine has an efficacy of 85% with minimal side effects. It is available in over 60 countries. However, it is not currently recommended by the Centers for Disease Control and Prevention (CDC) for most people traveling from the United States to the third world. One injectable vaccine was found to be effective for 2–3 years. It however has limited availability as of 2010. Work is under way to investigate the role of mass vaccination. The World Health Organization (WHO) recommends immunization of high risk groups such as children and people with HIV in countries where this disease is endemic. If people are immunized broadly herd immunity results with a decrease in the amount of contamination in the environment.
Cholera patient being treated by medical staff in 1992. Fluids
In most cases cholera can be successfully treated with oral rehydration therapy (ORT) which is highly effective, safe, and simple to administer. Rice based solutions are preferred to glucose based ones due to greater efficacy. In severe cases with significant dehydration intravenous rehydration may be necessary. Ringer's lactate is the preferred solution. Large volumes and continued replacement until diarrhea has subsided may be needed. 10% of a person's body weight in fluid may need to be given in the first 2 to 4 hours.
If commercially produced oral rehydration solutions are too expensive or difficult to obtain, solutions can be made. One such recipe calls for 1 liter of boiled water, 1 teaspoon of salt, 8 teaspoons of sugar, and added mashed banana for potassium and to improve taste.
As there frequently is initially acidosis, the potassium level may be normal even though large losses have occurred. As the dehydration is corrected potassium levels may decrease rapidly and thus need to be replaced.
Antibiotics for 1 to 3 days shorten the course of the disease and reduce the severity of the symptoms. People will however recover without them if sufficient hydration is maintained. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance. Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics that have been proven effective include cotrimoxazole, erythromycin, tetracycline, chloramphenicol, and furazolidone. Fluoroquinolones such as norfloxacin also may be used, but resistance has been reported.
In many areas of the world antibiotic resistance is increasing. In Bangladesh for example most cases of V. Cholerea are resistant to tetracycline, trimethoprim-sulfamethoxazole, and erythromycin. Rapid diagnostic assay methods are available for the identification of multi-drug resistant cases. New generation antimicrobials have been discovered which are effective against V. cholerae in in vitro studies.
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%.
It is estimated that worldwide cholera affects 3-5 million people 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.
Cholera likely has its origins in the Indian subcontinent being prevalent in the Ganges delta since ancient times. The disease first spread by trade routes (land and sea) to Russia in 1817, then to Western Europe, and from Europe to North America. John Snow in 1854 was the first to identify the importance of contaminated water in its cause. Cholera became the first reportable disease in the United States due to the significant effects it had on health. 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.
The word cholera is from Greek: χολέρα kholera from χολή kholē "bile".
Hand bill from the New York City Board of Health, 1832. The outdated public health advice demonstrates the lack of understanding of the disease and its actual causative factors.1816-1826 - First cholera pandemic: Previously restricted, the pandemic began in Bengal, and then spread across India by 1820. 10,000 British troops, and many times this number of Indians, died during this pandemic. The cholera outbreak extended as far as China, Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea before receding. Deaths in India between 1817 and 1860 are estimated to have exceeded 15 million people. Another 23 million died between 1865 and 1917. Russian deaths during a similar time period exceeded 2 million.
1829-1851 - Second cholera pandemic reached Russia (see Cholera Riots), Hungary (about 100,000 deaths) and Germany in 1831, London (more than 55,000 people died in the United Kingdom) and Paris in 1832. In London, the disease claimed 6,536 victims and came to be known as "King Cholera"; in Paris, 20,000 succumbed (out of a population of 650,000) with about 100,000 deaths in all of France. The epidemic reached Quebec, Ontario and New York in the same year and the Pacific coast of North America by 1834. The 1831 cholera epidemic killed 150,000 people in Egypt. In 1846, cholera struck Mecca, killing over 15,000 people. A two-year outbreak began in England and Wales in 1848 and claimed 52,000 lives.
1849 - Second major outbreak in Paris. In London, it was the worst outbreak in the city's history, claiming 14,137 lives, over twice as many as the 1832 outbreak. Cholera hit Ireland in 1849 and killed many of the Irish Famine survivors already weakened by starvation and fever. In 1849 cholera claimed 5,308 lives in the port city of Liverpool, England, and 1,834 in Hull, England. An outbreak in North America took the life of former U.S. President James K. Polk. Cholera, believed spread from ship(s) from England, spread throughout the Mississippi river system killing over 4,500 in St. Louis and over 3,000 in New Orleans as well as thousands in New York. It claimed 200,000 victims in Mexico. In 1849 cholera was spread along the California, Mormon and Oregon Trails as 6,000 to 12,000 are believed to have died on their way to the California Gold Rush, Utah and Oregon in the cholera years of 1849-1855. It is believed that over 150,000 Americans died during the two pandemics between 1832 and 1849.
1852-1860 - Third cholera pandemic mainly affected Russia, with over a million deaths. In 1852, cholera spread east to Indonesia and later invaded China and Japan in 1854. The Philippines were infected in 1858 and Korea in 1859. In 1859, an outbreak in Bengal once again led to the transmission of the disease to Iran, Iraq, Arabia and Russia. There were at least seven major outbreaks of cholera in Japan between 1858 and 1902. The Ansei outbreak of 1858-60, for example, is believed to have killed between 100,000 and 200,000 people in Tokyo alone.
1854 - Outbreak of cholera in Chicago took the lives of 5.5% of the population (about 3,500 people). In 1853-4, London's epidemic claimed 10,738 lives. The Soho outbreak in London ended after removal of the handle of the Broad Street pump by a committee instigated to action by John Snow. This proved that contaminated water (although it didn't identify the contaminant) was the main agent spreading cholera. It would take many years for this message to be believed and acted upon. Throughout Spain, cholera caused more than 236,000 deaths in 1854–55. In 1854 and 1855 it entered Venezuela; Brazil also suffered in 1855.
1863-1875 - Fourth cholera pandemic spread mostly in Europe and Africa. At least 30,000 of the 90,000 Mecca pilgrims fell victim to the disease. Cholera ravaged Africa in 1865. Traveling southeastwards, cholera reached Zanzibar, where 70,000 people are reported to have died in 1869–70. Cholera claimed 90,000 lives in Russia in 1866. The epidemic of cholera that spread with the Austro-Prussian War (1866) is estimated to have claimed 165,000 lives in the Austrian Empire. Hungary and Belgium both lost 30,000 people and in the Netherlands 20,000 perished. In 1867, Italy lost 113,000 lives. That same year, cholera traveled to Algeria and killed 80,000.
1892 cholera outbreak in Hamburg, hospital ward
1892 cholera outbreak in Hamburg, disinfection team1866 - 1873 - Outbreaks in North America. It killed some 50,000 Americans. In London, a localized epidemic in the East End claimed 5,596 lives just as London was completing its major sewage and water treatment systems—the East End was not quite complete. William Farr, using the work of John Snow et al. as to contaminated drinking water being the likely source of the disease, was able to relatively quickly identify the East London Water Company as the source of the contaminated water. Quick action prevented further deaths. Also a minor outbreak at Ystalyfera in South Wales. Caused by the local water works using contaminated canal water, it was mainly its workers and their families who suffered, 119 died. In the same year more than 21,000 people died in Amsterdam, The Netherlands. In the 1870s, cholera spread in the US as epidemic from New Orleans along the Mississippi River and related ports of tributaries, with thousands dying.
1881-1896 - Fifth cholera pandemic; According to Dr A. J. Wall, the 1883-1887 epidemic cost 250,000 lives in Europe and at least 50,000 in Americas. Cholera claimed 267,890 lives in Russia (1892); 120,000 in Spain; 90,000 in Japan and over 60,000 in Persia. In Egypt cholera claimed more that 58,000 lives. The 1892 outbreak in Hamburg killed 8,600 people. Although generally held responsible for the virulence of the epidemic, the city government went largely unchanged. This was the last serious European cholera outbreak.
1899-1923 - Sixth cholera pandemic had little effect in Europe because of advances in public health, but major Russian cities (more than 500,000 people dying of cholera during the first quarter of the 20th century) and the Ottoman Empire were particularly hard hit by cholera deaths. The 1902-1904 cholera epidemic claimed 200,000 lives in the Philippines. 27 epidemics were recorded during pilgrimages to Mecca from the 19th century to 1930, and more than 20,000 pilgrims died of cholera during the 1907–08 hajj. The sixth pandemic killed more than 800,000 in India. The last outbreak in the United States was in 1910-1911 when the steamship Moltke brought infected people to New York City. Vigilant health authorities isolated the infected on Swinburne Island. Eleven people died, including a health care worker on Swinburne Island.
1961–Present - Seventh cholera pandemic began in Indonesia, called El Tor after the strain, and reached East Pakistan (now Bangladesh) in 1963, India in 1964, and the USSR in 1966. From North Africa it spread into Italy by 1973. In the late 1970s, there were small outbreaks in Japan and in the South Pacific. There were also many reports of a cholera outbreak near Baku in 1972, but information about it was suppressed in the USSR.
Amplified fragment length polymorphism (AFLP) fingerprinting of the pandemic isolates of Vibrio cholerae has revealed variation in the genetic structure. Two clusters have been identified: Cluster I and Cluster II. For the most part Cluster I consists of strains from the 1960s and 1970s, while Cluster II largely contains strains from the 1980s and 1990s, based on the change in the clone structure. This grouping of strains is best seen in the strains from the African Continent.
 Notable outbreaks
By 12 February 2009, the number of cases of infection by cholera in sub-Saharan Africa had reached 128,548 and the number of fatalities, 4,053.November 2010 - In November of 2010, it was reported that the cholera outbreak that began in Haiti the previous month had spread into the Dominican Republic. It was also reported that the cholera outbreak has reached Florida from a woman who had visited Haiti.
October 2010 - In late October a cholera outbreak was reported in Haiti, and as of November 16th the Haitian Health Ministry reported the number of dead to be 1,034, with hospitalizations for cholera symptoms totaling over 16,700. It is feared that the epidemic could accelerate due to standing water left by a recent hurricane and the fact that over one-tenth of the population remain living in close quarters in tents in refugee camps without adequate sanitation since the Haiti earthquake in January.
August 2010 - Nigeria is reaching epidemic proportions after wide spread confirmation of the Cholera outbreaks in 12 of its 36 states. 6400 cases have been reported with 352 reported deaths. The health ministry blamed the outbreak on heavy seasonal rainfall and poor sanitation.
January 2009 - The Mpumalanga province of South Africa has confirmed over 381 new cases of Cholera, bringing the total number of cases treated since November 2008 to 2276. 19 people have died in the province since the outbreak.
August 2008 - April 2009: In the 2008 Zimbabwean cholera outbreak, which is still continuing, an estimated 96,591 people in the country have been infected with cholera and, by 16 April 2009, 4,201 deaths had been reported. According to the World Health Organization, during the week of 22–28 March 2009, the "Crude Case Fatality Ratio (CFR)" had dropped from 4.2% to 3.7%. The daily updates for the period 29 March 2009 to 7 April 2009, list 1748 cases and 64 fatalities, giving a weekly CFR of 3.66% (see table above); however, those for the period 8 April to 16 April list 1375 new cases and 62 deaths (and a resulting CFR of 4.5%). The CFR had remained above 4.7% for most of January and early February 2009.
November 2008 - Doctors Without Borders reported an outbreak in a refugee camp in the Democratic Republic of the Congo's eastern provincial capital of Goma. Some 45 cases were reportedly treated between November 7 through 9th.
August - October 2008 - As of 29 October 2008, a total of 644 laboratory-confirmed cholera cases, including eight deaths, had been verified in Iraq.
March - April 2008 - 2,490 people from 20 provinces throughout Vietnam have been hospitalized with acute diarrhea. Of those hospitalized, 377 patients tested positive for cholera.
August 2007 - The cholera epidemic started in Orissa, India. The outbreak has affected Rayagada, Koraput and Kalahandi districts where more than 2,000 people have been admitted to hospitals.
July - December 2007 - A lack of clean drinking water in Iraq has led to an outbreak of cholera. As of 2 December 2007, the UN has reported 22 deaths and 4,569 laboratory-confirmed cases.
In 2000, some 140,000 cholera cases were officially notified to WHO. Africa accounted for 87% of these cases.
January 1991 to September 1994 - Outbreak in South America, apparently initiated when a ship discharged ballast water. Beginning in Peru there were 1.04 million identified cases and almost 10,000 deaths. The causative agent was an O1, El Tor strain, with small differences from the seventh pandemic strain. In 1992 a new strain appeared in Asia, a non-O1, nonagglutinable vibrio (NAG) named O139 Bengal. It was first identified in Tamil Nadu, India and for a while displaced El Tor in southern Asia before decreasing in prevalence from 1995 to around 10% of all cases. It is considered to be an intermediate between El Tor and the classic strain and occurs in a new serogroup. There is evidence of the emergence of wide-spectrum resistance to drugs such as trimethoprim, sulfamethoxazole and streptomycin.
 False historical report
Main article: Chicago 1885 cholera epidemic myth
A persistent myth states that 90,000 people died in Chicago of cholera and typhoid fever in 1885, but this story has no factual basis. In 1885, there was a torrential rainstorm that flushed the Chicago River and its attendant pollutants into Lake Michigan far enough that the city's water supply was contaminated. However, because cholera was not present in the city, there were no cholera-related deaths. Nevertheless, the incident caused the city to become more serious about its sewage treatment.
 Cholera morbus
The term cholera morbus was used in the 19th and early 20th centuries to describe both non-epidemic cholera and other gastrointestinal diseases (sometimes epidemic) that resembled cholera. The term is not in current use, but is found in many older references. The other diseases are now known collectively as gastroenteritis.
 Other historical information
In the past, people traveling in ships would hang a yellow quarantine flag if one or more of the crew members suffered from cholera. Boats with a yellow flag hung would not be allowed to disembark at any harbor for an extended period, typically 30 to 40 days. In modern international maritime signal flags the quarantine flag is yellow and black.
The Russian-born bacteriologist Waldemar Haffkine developed the first cholera vaccine around 1900. The bacterium had been originally isolated forty five years earlier (1855) by Italian anatomist Filippo Pacini, but its exact nature and his results were not widely known around the world.
One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist John Snow (1813–1858), who found a link between cholera and contaminated drinking water in 1854. 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 aetiology of the disease. In two pioneering epidemiological field-studies, he was able to demonstrate that human sewage contamination was the most probable disease vector in two major epidemics in London in 1854. His model was not immediately accepted, but it was seen to be the more plausible as medical microbiology developed over the next thirty years or so.
Cities in developed nations made massive investment in clean water supply and well-separated sewage treatment infrastructures was made between the mid-1850s and the 1900s. This eliminated the threat of cholera epidemics from the major developed cities in the world. Robert Koch, 30 years later, identified V. cholerae with a microscope as the bacillus causing the disease in 1885.
Cholera has been a laboratory for the study of evolution of virulence. The province of Bengal in British India was partitioned into West Bengal and East Pakistan in 1947. Prior to partition, both regions had cholera pathogens with similar characteristics. After 1947, India made more progress on public health than East Pakistan (now Bangladesh). As a consequence,[clarification needed] the strains of the pathogen that succeeded in India had a greater incentive in the longevity of the host. They have become less virulent than the strains prevailing in Bangladesh. These uninhibitedly draw upon the resources of the host population, thus rapidly killing many victims.
More recently, in 2002, Alam et al. studied stool samples from patients at the International Centre for Diarrhoeal Disease (ICDDR) in Dhaka, Bangladesh. From the various experiments they conducted, the researchers found a correlation between the passage of V. cholerae through the human digestive system and an increased infectivity state. Furthermore, the researchers found that the bacterium creates a hyper-infected state where genes that control biosynthesis of amino acids, iron uptake systems, and formation of periplasmic nitrate reductase complexes were induced just before defecation. These induced characteristics allow the cholera vibrios to survive in the "rice water" stools, an environment of limited oxygen and iron, of patients with a cholera infection.
 Society and culture
 Notable cases
Tchaikovsky's death has traditionally been attributed to cholera, most probably contracted through drinking contaminated water several days earlier. Since the water was not boiled and cholera was once again rampaging St. Petersburg, such a connection was quite plausible ...." However, some, including English musicologist and Tchaikovsky authority David Brown and biographer Anthony Holden, have theorized that his death was a suicide. It should be noted also that Tchaikovsky's mother died of cholera, and his father became sick with cholera at this time but made a full recovery.
Elliott Frost, son of American poet Robert Frost
 Literary works
The Ghost Map: The Story of London's Most Terrifying Epidemic - and How it Changed Science, Cities and the Modern World - which tells the story of how John Snow found the cause of a cholera epidemic, which was the start of modern epidemiology.
The Painted Veil, starring Naomi Watts and Edward Norton, in which cholera is a prominent subject, based on the novel of the same name by W. Somerset Maugham.
The Horseman on the Roof (1995 film), starring Juliette Binoche and Olivier Martinez, in which the 1832 cholera outbreak in southern France is a major influence to the story line.
The Dress Lodger by Sheri Holman - A historical novel set in Sunderland, England during the cholera epidemic of 1831.
In the novel Death in Venice by Thomas Mann (also a 1971 film by Lucino Visconti starring Dirk Bogard), the main character dies of cholera in Venice; the epidemic is a recurring sub-plot of the story.
Love in the Time of Cholera, a novel by Nobel Prize winning Colombian author Gabriel García Márquez, and its English-language film adaptation.
In Mary Shelley's Frankenstein, while Victor is preparing his creation, Ingolstadt is struck by a cholera outbreak which actually turns out to be pneumonia.
In The Secret Garden, cholera orphans the main character. http://en.wikipedia.org/wiki/Cholera