cholera cholera cholera (/ˈkɒlərə/) is an infection of the small intestine by some strains of the bacterium vibrio cholerae. symptoms may range from none, to mild, to severe. the classic symptom is large amounts of watery diarrhea that lasts a few days. vomiting and muscle cramps may also occur. diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance. this may result in sunken eyes, cold skin, decreased skin elasticity, and wrinkling of the hands and feet. dehydration can cause the skin to turn bluish. symptoms start two hours to five days after exposure. choleraother namesasiatic cholera, epidemic choleraa person with severe dehydration due to cholera, causing sunken eyes and wrinkled hands and skin.specialtyinfectious diseasesymptomslarge amounts of watery diarrhea, vomiting, muscle crampscomplicationsdehydration, electrolyte imbalanceusual onset2 hours to 5 days after exposuredurationa few dayscausesvibrio cholerae spread by fecal-oral routerisk factorspoor sanitation, not enough clean drinking water, povertydiagnostic methodstool testpreventionimproved sanitation, clean water, hand washing, cholera vaccinestreatmentoral rehydration therapy, zinc supplementation, intravenous fluids, antibioticsprognosisless than 1% mortality rate with proper treatment, untreated mortality rate 50-60%frequency3–5 million people a yeardeaths28,800 (2015) cholera is caused by a number of types of vibrio cholerae, with some types producing more severe disease than others. it is spread mostly by unsafe water and unsafe food that has been contaminated with human feces containing the bacteria. undercooked shellfish is a common source. humans are the only known host for the bacteria. risk factors for the disease include poor sanitation, insufficient clean drinking water, and poverty. cholera can be diagnosed by a stool test, or a rapid dipstick test, although the dipstick test is less accurate. prevention methods against cholera include improved sanitation and access to clean water. cholera vaccines that are given by mouth provide reasonable protection for about six months, and have the added benefit of protecting against another type of diarrhea caused by e. coli. in 2017 the us food and drug administration (fda) had approved a single-dose, live, oral cholera vaccine called vaxchora for adults aged 18–64 who are travelling to an area of active cholera transmission. it offers limited protection to young children. people who survive an episode of cholera have long-lasting immunity for at least 3 years (the period tested.) the primary treatment for affected individuals is oral rehydration salts (ors), the replacement of fluids and electrolytes by using slightly sweet and salty solutions. rice-based solutions are preferred. in children, zinc supplementation has also been found to improve outcomes. in severe cases, intravenous fluids, such as ringer's lactate, may be required, and antibiotics may be beneficial. the choice of antibiotic is aided by antibiotic sensitivity testing. cholera continues to affect an estimated 3–5 million people worldwide and causes 28,800–130,000 deaths a year. to date, seven cholera pandemics have occurred in the developing world, with the most recent beginning in 1961, and continuing today. the illness is rare in high-income countries, and effects children most severely. cholera occurs as both outbreaks and chronically in certain areas. areas with an ongoing risk of disease include africa and southeast asia. the risk of death among those affected is usually less than 5%, given improved treatment, but may be as high as 50% without such access to treatment. descriptions of cholera are found as early as the 5th century bc in sanskrit. in europe, cholera was a term initially used to describe any kind of gastroenteritis, and was not used for this disease until the early 19th century. the study of cholera in england by john snow between 1849 and 1854 led to significant advances in the field of epidemiology because of his insights about transmission via contaminated water, and a map of the same was the first recorded incidence of epidemiological tracking. signs and symptoms typical cholera diarrhea that looks like "rice water" the primary symptoms of cholera are profuse diarrhea and vomiting of clear fluid. these symptoms usually start suddenly, half a day 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 to 20 litres (3 to 5 us gal) of diarrhea a day. severe cholera, without treatment, kills about half of affected individuals. if the severe diarrhea is not treated, it can result in life-threatening dehydration and electrolyte imbalances. estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100. cholera has been nicknamed the "blue death" because a person's skin may turn bluish-gray from extreme loss of fluids. fever is rare and should raise suspicion for secondary infection. patients can be lethargic and might have sunken eyes, dry mouth, cold clammy skin, or wrinkled hands and feet. kussmaul breathing, a deep and labored breathing pattern, can occur because of acidosis from stool bicarbonate losses and lactic acidosis associated with poor perfusion. blood pressure drops due to dehydration, peripheral pulse is rapid and thready, and urine output decreases with time. muscle cramping and weakness, altered consciousness, seizures, or even coma due to electrolyte imbalances are common, especially in children. cause main article: vibrio cholerae scanning electron microscope image of vibrio cholerae vibrio cholerae, the bacterium that causes cholera transmission cholera bacteria have been found in shellfish and plankton. transmission is usually through the fecal-oral route of contaminated food or water caused by poor sanitation. most cholera cases in developed countries are a result of transmission by food, while in developing countries it is more often water. 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. 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. a single diarrheal event can cause a one-million fold increase in numbers of v. cholerae in the environment. the source of the contamination is typically other people with cholera 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. 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. 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. specifically, animal models indicate that the transcriptional profile of the pathogen changes as it prepares to enter an aquatic environment. 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). 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. both toxic and non-toxic strains exist. non-toxic strains can acquire toxicity through a temperate bacteriophage. susceptibility about 100 million bacteria must typically be ingested to cause cholera in a normal healthy adult. this dose, however, is less in those with lowered gastric acidity (for instance those using proton pump inhibitors). children are also more susceptible, with two- to four-year-olds having the highest rates of infection. individuals' susceptibility to cholera is also affected by their blood type, with those with type o blood being the most susceptible. persons with lowered immunity, such as persons with aids or malnourished children, are more likely to develop a severe case if they become infected. any individual, even a healthy adult in middle age, can undergo 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. 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 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 intestinal epithelium, thus reducing the effects of an infection. mechanism 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. 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. once the cholera bacteria reach the intestinal wall, they no longer need the flagella to move. the bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins that they express 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 the secretion of water, sodium, potassium, and bicarbonate into the lumen of the small intestine and rapid dehydration. the gene encoding the cholera toxin was introduced into v. cholerae by horizontal gene transfer. virulent strains of v. cholerae carry a variant of a temperate bacteriophage called ctxφ. 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 unless treated properly. 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 a complex cascade of regulatory proteins controls 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, causing diarrhea