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Cholera is an
infection An infection is the invasion of an organism's body tissues by disease-causing agents, their multiplication, and the reaction of host A host is a person responsible for guests at an event or for providing hospitality during it. Host may ...

infection
of the
small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

small intestine
by some strains of the
bacterium Bacteria (; common noun bacteria, singular bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell The cell (from Latin ''cella'', meaning "small room") is the basic structural, functional, and ...

bacterium
''
Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative Gram-negative bacteria are bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), domain o ...

Vibrio cholerae
''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery defecation, bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration of ...
that lasts a few days.
Vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach The stomach is a muscular, in the of humans and many other animals, including several s. The stomach has a dilat ...

Vomiting
and
muscle cramps A cramp is a sudden, involuntary muscle contraction or overshortening; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the affected muscle. Muscle cramps are common and are often as ...
may also occur. Diarrhea can be so severe that it leads within hours to severe
dehydration In physiology, dehydration is a lack of total body water In physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology Biology is the natural science that studie ...

dehydration
and
electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes An electrolyte is a substance that produces an electrically conducting solution when dissolved in a polar solvent, such as water. The di ...
. 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. Cholera is caused by a number of
types Type may refer to: Science and technology Computing * Typing Typing is the process of writing or inputting text by pressing keys on a typewriter, computer keyboard, cell phone, or calculator. It can be distinguished from other means of text inpu ...

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 Human feces (or faeces in British English British English (BrE) is the standard dialect A standard language (also standard variety, standard dialect, and standard) is a language variety that has undergone substantial codification of gra ...

human feces
containing the bacteria. Undercooked
seafood Seafood is any form of sea life regarded as food by humans, prominently including fish Fish are , , -bearing animals that lack with . Included in this definition are the living , s, and and as well as various extinct related groups. ...

seafood
is a common source. Humans are the only animal affected.
Risk factors In epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants In mathematics, the determinant is a Scalar (mathematics), scalar value that is a function (mathematics), function ...
for the disease include poor
sanitation Sanitation refers to public health Public health has been defined as "the science and art of preventing disease", prolonging life and improving quality of life Quality of life (QOL) is defined by the World Health Organization The ...

sanitation
, not enough clean
drinking water Drinking water, also known as potable water, is water that is safe to drinking, drink or use for food preparation. The amount of drinking water required to maintain good health varies, and depends on physical activity level, age, health-related ...

drinking water
, and
poverty Poverty is the state of having little material possessions or income In microeconomics, income is the Consumption (economics), consumption and saving opportunity gained by an entity within a specified timeframe, which is generally expresse ...

poverty
. There are concerns that
rising sea level Tide gauge measurements show that the current global sea level rise began at the start of the 20th century. Between 1900 and 2017, the globally averaged sea level Mean sea level (MSL) (often shortened to sea level) is an mean, average level ...
s will increase rates of disease. Cholera can be diagnosed by a
stool test A stool test involves the collection and analysis of fecal matter to diagnose the presence or absence of a medical condition. Visual examination The patient and/or health care worker in the office or at the bedside is able to make some important ob ...
. A rapid dipstick test is available but is not as accurate. Prevention methods against cholera include improved sanitation and access to
clean water Drinking water, also known as potable water, is water Water is an Inorganic compound, inorganic, Transparency and translucency, transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance, which is the main ...

clean water
.
Cholera vaccine Cholera vaccines are vaccine A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often m ...
s that are given by mouth provide reasonable protection for about six months. They have the added benefit of protecting against another type of diarrhea caused by ''''. The primary treatment is
oral rehydration therapy Oral rehydration therapy (ORT) is a type of fluid replacement used to prevent and treat dehydration, especially due to diarrhea. It involves drinking water with modest amounts of sugar and salts, specifically sodium and potassium. Oral rehydratio ...
—the replacement of fluids with slightly sweet and salty solutions. Rice-based solutions are preferred.
Zinc supplementation Zinc deficiency is defined either as insufficient zinc Zinc is a chemical element with the Symbol (chemistry), symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a silvery-greyish appearance when oxi ...
is useful in children. In severe cases,
intravenous fluid Intravenous therapy (abbreviated as IV therapy) is a medical technique that delivers fluids, medications and nutrition directly into a person's vein Veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood f ...
s, such as
Ringer's lactate Ringer's lactate solution (RL), also known as sodium lactate solution and Hartmann's solution, is a mixture of sodium chloride Sodium chloride , commonly known as salt (although sea salt also contains other chemical salt (chemistry), salts), ...
, may be required, and
antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is any organic, life, living system t ...
s may be beneficial. Testing to see which antibiotic the cholera is susceptible to can help guide the choice. Cholera affects an estimated 3–5 million people worldwide and causes 28,800–130,000 deaths a year. Although it is classified as a
pandemic A pandemic (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approx ...

pandemic
, it is rare in
high income countries A high-income economy is defined by the World Bank The World Bank is an international financial institution An international financial institution (IFI) is a financial institution that has been established (or chartered) by more than one count ...
. Children are mostly affected. Cholera occurs as both
outbreaks In epidemiology, an outbreak is a sudden increase in occurrences of a disease when cases are in excess of normal expectancy for the location or season. It may affect a small and localized group or impact upon thousands of people across an entire c ...
and chronically in certain areas. Areas with an ongoing risk of disease include
Africa Africa is the world's second-largest and second-most populous continent A continent is any of several large landmass A landmass, or land mass, is a large region In geography Geography (from Greek: , ''geographia'', ...

Africa
and
Southeast Asia Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia or SEA, is the geographical United Nations geoscheme for Asia#South-eastern Asia, southeastern subregion of Asia, consisting of the regions ...

Southeast Asia
. The risk of death among those affected is usually less than 5% but may be as high as 50%. No access to treatment results in a higher death rate. Descriptions of cholera are found as early as the 5th century BC in
Sanskrit Sanskrit (; attributively , ; nominalization, nominally , , ) is a classical language of South Asia that belongs to the Indo-Aryan languages, Indo-Aryan branch of the Indo-European languages. It arose in South Asia after its predecessor langua ...

Sanskrit
. The study of cholera in England by
John Snow John Snow (15 March 1813 – 16 June 1858) was an English physician and a leader in the development of anaesthesia and medical hygiene. He is considered one of the founders of modern epidemiology, in part because of his work in tracing the s ...
between 1849 and 1854 led to significant advances in the field of
epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and risk factor, determinants of health and disease conditions in defined populations. It is a cornerstone of public health, and shapes policy decisions ...
. Seven large outbreaks have occurred over the last 200 years with millions of deaths.


Signs and symptoms

The primary symptoms of cholera are profuse
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery defecation, bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration of ...
and
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach The stomach is a muscular, in the of humans and many other animals, including several s. The stomach has a dilat ...

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 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 In physiology, dehydration is a lack of total body water In physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology Biology is the natural science that studie ...

dehydration
and
electrolyte An electrolyte is a medium containing ions that is electrically conducting Electrical resistivity (also called specific electrical resistance or volume resistivity) is a fundamental property of a material that quantifies how strongly it resis ...

electrolyte
imbalances. Estimates of the ratio of
asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplicatio ...
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 Kussmaul breathing is a deep and labored breathing pattern often associated with severe metabolic acidosis, particularly diabetic ketoacidosis Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus Dia ...

Kussmaul breathing
, a deep and labored breathing pattern, can occur because of
acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes th ...

acidosis
from
bicarbonate In inorganic chemistry, bicarbonate (International Union of Pure and Applied Chemistry, IUPAC-recommended nomenclature: hydrogen carbonate) is an intermediate form in the deprotonation of carbonic acid. It is a Polyatomic ion, polyatomic anion w ...

bicarbonate
losses and
lactic acidosis Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate Lactic acid is an organic acid. It has a molecular formula CH3CH(OH)COOH. It is white in the solid state and it is miscibility, miscible with w ...
associated with poor
perfusion Perfusion is the passage of fluid through the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a biological system A biological system is a c ...
.
Blood pressure Blood pressure (BP) is the pressure Pressure (symbol: ''p'' or ''P'') is the force In physics, a force is an influence that can change the motion (physics), motion of an Physical object, object. A force can cause an object with mas ...

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 An epileptic seizure, formally known as a seizure, is a period of symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower tem ...
, or even
coma A coma is a deep state of prolonged unconsciousness Unconsciousness is a state which occurs when the ability to maintain an consciousness, awareness of self and environment is lost. It involves a complete, or near-complete, lack of responsive ...
due to
electrolyte imbalance Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes An electrolyte is a substance that produces an electrically conducting solution when dissolved in a polar solvent, such as water. The di ...
s are common, especially in children.


Cause


Transmission

Cholera bacteria have been found in
shellfish Shellfish is a colloquial and fisheries Fishery is the enterprise of raising or harvesting fish and other aquatic life. Commercial fisheries include wild fisheries and Fish farming, fish farms, both in fresh water (about 10% of all catch) and ...

shellfish
and
plankton Plankton are the diverse collection of organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology ...

plankton
.
Transmission Transmission may refer to: Science and technology * Power transmissionPower transmission is the movement of energy from its place of generation to a location where it is applied to perform useful Mechanical work, work. Power (physics), Power is d ...
is usually through the fecal-oral route of contaminated food or water caused by poor
sanitation Sanitation refers to public health Public health has been defined as "the science and art of preventing disease", prolonging life and improving quality of life Quality of life (QOL) is defined by the World Health Organization The ...

sanitation
. Most cholera cases in
developed countries A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state A sovereign state is a political entity that is represented by one centralized governmen ...
are a result of transmission by food, while in
developing countries A developing country is a sovereign state with a less developed Industrial sector, industrial base and a low Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no ...
it is more often water. Food transmission can occur when people harvest seafood such as
oyster Oyster is the common name Common may refer to: Places * Common, a townland in County Tyrone, Northern Ireland * Boston Common Boston Common (also known as the Common) is a central public park in downtown Boston, Massachusetts. It is someti ...

oyster
s in waters infected with
sewage Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater Wastewater is generated after the use of fresh water Water (chemical formula H2O) is an inorganic, transparent, tasteless, odorless, and n ...
, as ''Vibrio cholerae'' accumulates in
plankton Plankton are the diverse collection of organism In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology ...

plankton
ic
crustaceans Crustaceans (Crustacea ) form a large, diverse arthropod An arthropod (, (gen. ποδός)) is an invertebrate Invertebrates are animals that neither possess nor develop a vertebral column (commonly known as a ''backbone'' or ''spine''), de ...

crustaceans
and the oysters eat the
zooplankton Zooplankton (; ) are heterotroph A heterotroph (; from Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often ro ...

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 cholera sufferers when their untreated diarrheal discharge is allowed to get into waterways,
groundwater Groundwater is the water Water (chemical formula H2O) is an , transparent, tasteless, odorless, and , which is the main constituent of 's and the s of all known living organisms (in which it acts as a ). It is vital for all known form ...

groundwater
or
drinking water Drinking water, also known as potable water, is water that is safe to drinking, drink or use for food preparation. The amount of drinking water required to maintain good health varies, and depends on physical activity level, age, health-related ...

drinking water
supplies. Drinking any contaminated water and eating any foods washed in the water, as well as
shellfish Shellfish is a colloquial and fisheries Fishery is the enterprise of raising or harvesting fish and other aquatic life. Commercial fisheries include wild fisheries and Fish farming, fish farms, both in fresh water (about 10% of all catch) and ...

shellfish
living in the affected
waterway A waterway is any navigable A body of water, such as a river, canal or lake, is navigable if it is deep, wide and calm enough for a water vessel (e.g. boats) to pass safely. Such a navigable water is called a ''waterway'', and is preferably w ...

waterway
, can cause a person to contract an infection. Cholera is rarely spread directly from person to person.According to
CDC CDC may refer to: Organizations Government * Centers for Disease Control and Prevention The United States The United States of America (USA), commonly known as the United States (U.S. or US), or America, is a country Contiguous Unite ...
,"The infection holerais not likely to spread directly from one person to another; therefore, casual contact with an infected person is not a risk factor for becoming ill."
''V. cholerae'' also exists outside the human body in natural water sources, either by itself or through interacting with
phytoplankton Phytoplankton () are the autotrophic An autotroph or primary producer is an organism that produces complex organic compound , CH4; is among the simplest organic compounds. In chemistry, organic compounds are generally any chemical compoun ...

phytoplankton
,
zooplankton Zooplankton (; ) are heterotroph A heterotroph (; from Ancient Greek Ancient Greek includes the forms of the Greek language used in ancient Greece and the classical antiquity, ancient world from around 1500 BC to 300 BC. It is often ro ...

zooplankton
, or
biotic Biotics describe living or once living components of a community; for example organisms, such as animals and plants. Biotic may refer to: *Life, the condition of living organisms *Biology, the study of life *Biotic material, which is derived from l ...
and 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 Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect on ...

toxicity
through a
temperate In geography Geography (from Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its populati ...
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, ...

bacteriophage
.


Susceptibility

About 100million bacteria must typically be ingested to cause cholera in a normal healthy adult. This dose, however, is less in those with lowered
gastric acid Gastric acid, gastric juice, or stomach acid, is a digestive fluid formed within the stomach lining. With a pH between 1 and 3, gastric acid An acid is a or capable of donating a (hydrogen ion H+) (a ), or, alternatively, capable of for ...
ity (for instance those using
proton pump inhibitors Proton-pump inhibitors (PPIs) are a class of medication A medication (also referred to as medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, therapy, treat, or preventive medici ...
). 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 A blood type (also known as a blood group) is a classification of blood Blood is a body fluid Body fluids, bodily fluids, or biofluids are liquid A liquid is a nearly incompressible In fluid mechanics or more generally continuum ...
, with those with
type O blood The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigen In immunology, an antigen (Ag) is a molecule or molecular structure, such as may be present on the outside of a pathogen, that can ...
being the most susceptible. Persons with lowered immunity, such as persons with
AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection An infection is the invasion of an organism's body by , their multiplication, and the reaction of ...
or
malnourished Malnutrition is a condition that results from eating a diet which does not supply a healthy amount of one or more nutrient A nutrient is a substance used by an organism to survive, grow, and reproduce. The requirement for dietary nutrient in ...
children, are more likely to experience a severe case if they become infected.Prevention and control of cholera outbreaks: WHO policy and recommendations
, World Health Organization, Regional Office for the Eastern Mediterranean, undated but citing sources from '07, '04, '03, '04, and '05.
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 A health care provider is an individual health professional A health professional (or healthcare professional) may provide health care Health care, health-care, or healthcare is the maintenance or improvement of health via the preventive healthca ...
. The
cystic fibrosis Cystic fibrosis (CF) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene In biology, a gene (from ''genos'' "...Wilhelm Johan ...
genetic
mutation In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechan ...
known as delta-F508 in humans has been said to maintain a selective heterozygous advantage:
heterozygous Zygosity (the noun, zygote, is from the Greek zygotos "yoked," from zygon "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an or ...

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 Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein Membrane proteins are common proteins that are part of, or interact with, biological membranes. Membrane proteins fall into several broad categories depending on the ...
channel proteins interferes with bacteria binding to the
intestinal epithelium The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract The gastrointestinal tract, (GI tract, GIT, digestive tract, digestion ...
, thus reducing the effects of an infection.


Mechanism

When consumed, most bacteria do not survive the
acidic An acid is a molecule A molecule is an electrically Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in position In phys ...
conditions of the . The few surviving bacteria conserve their energy and stored
nutrient A nutrient is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of attributes * Chemical substance, a material with a definite chemical composition * Matter, anything that has mass and t ...
s during the passage through the stomach by shutting down
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

protein
production. When the surviving bacteria exit the stomach and reach the
small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

small intestine
, they must propel themselves through the thick
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membrane A mucous membrane or mucosa is a biological membrane, membrane that lines various cavities in the body and covers the surface of internal organs. It consists o ...

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 A flagellum (; ) is a hairlike appendage that protrudes from a wide range of microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology Biology is the natural science that studies life and ...
to move. The bacteria stop producing the protein
flagellin '' Helicobacter pylori'' electron micrograph, showing multiple flagella on the cell surface Flagellin is a globular protein that arranges itself in a hollow cylinder to form the filament in a bacterial flagellum. It has a mass of about 30,000 to ...
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 Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex is a protein complex functioning as a molecular biological machine. It uses protein domain dynamics on nanoscales A protei ...

cholera toxin
(CTX or CT) is an
oligomer In chemistry Chemistry is the scientific Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity or awareness, of someone or something, such as facts A fact is an occurrence in ...
ic complex made up of six
protein subunit 274px, Rendering of HLA-A11 showing the α (A*1101 gene product) and β (Beta-2 microglobin) subunits. This receptor has a bound peptide (in the binding pocket) of heterologous origin that also contributes to function. In structural biology, a p ...
s: a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a
disulfide bond In biochemistry Biochemistry or biological chemistry, is the study of chemical process In a scientific Science (from the Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-Europe ...
. The five B subunits form a five-membered ring that binds to
ganglioside A ganglioside is a molecule composed of a glycosphingolipidImage:Sphingosine structure.svg, Sphingosine Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They may be considered as sphingolipids with an atta ...
s on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates
G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), c ...

G protein
s, 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 Endocytosis is a in which are brought into the cell. The material to be internalized is surrounded by an area of , which then buds off inside the cell to form a containing the ingested material. Endocytosis includes (cell drinking) and (cell ...

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 The Gs alpha subunit (Gαs, Gsα) is a subunit of the heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPase Small GTPases (), ...
of the
heterotrimeric G protein Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPase Small GTPases (), also known as small G-proteins, are a family of hydrolase enzymes that can bin ...
. This results in constitutive
cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to describ ...
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 Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular A unicellular organism, also known as a single-celled organism, is an organism In biology, an organism (from Ancient G ...
. Virulent strains of ''V. cholerae'' carry a variant of a
temperate In geography Geography (from Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its populati ...
bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a virus A virus is a submicroscopic infectious agent In biology Biology is the natural science that studies life and living organisms, including their anatomy, ...

bacteriophage
called CTXφ. Microbiologists have studied the gene expression, 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."Cholera Fact Sheet", World Health Organization
who.int
. Retrieved November 5, 2013.
By inserting separate, successive sections of ''V. cholerae'' DNA into the DNA of other bacteria, such as ''Escherichia coli, 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 in the infected person and allowing 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."


Genetic structure

Amplified fragment length polymorphism DNA profiling, fingerprinting of the pandemic genetic isolate, isolates of ''V. cholerae'' has revealed variation in the genetic structure. Two gene cluster, 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.


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. Rapid diagnostic assay methods are available for the identification of multiple drug resistance, multi-drug resistant cases. New generation antimicrobials have been discovered which are effective against cholera bacteria in ''in vitro'' studies.


Diagnosis

A rapid dipstick test is available to determine the presence of ''V. cholerae''. In those samples that test positive, further testing should be done to determine antibiotic resistance. In epidemic situations, a clinical diagnosis may be made by taking a medical history, patient history and doing a brief examination. Treatment is usually started without or before confirmation by laboratory analysis. 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 ''V. cholerae'' O1. If ''V. cholerae'' serotype, 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.


Prevention

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


Water, sanitation and hygiene

Although cholera may be life-threatening, prevention of the disease is normally straightforward if proper
sanitation Sanitation refers to public health Public health has been defined as "the science and art of preventing disease", prolonging life and improving quality of life Quality of life (QOL) is defined by the World Health Organization The ...

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. Cholera is mainly a risk in
developing countries A developing country is a sovereign state with a less developed Industrial sector, industrial base and a low Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no ...
in those areas where access to WASH, WASH (water, sanitation and hygiene) infrastructure is still inadequate. 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 all materials that may have come into contact with cholera victims' feces (e.g., clothing, bedding, etc.) are essential. These should be Disinfection, 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 Sanitation refers to public health Public health has been defined as "the science and art of preventing disease", prolonging life and improving quality of life Quality of life (QOL) is defined by the World Health Organization The ...

sanitation
and hygiene is an important preventative measure. Open defecation, release of untreated sewage, or dumping of fecal sludge from pit latrines or septic tanks into the environment need to be prevented. In many cholera affected zones, there is a low degree of sewage treatment. 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. * Sources: Warnings about possible cholera contamination should be posted around contaminated water sources with directions on how to decontamination, 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, Water chlorination, 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, 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. Hand washing, Handwashing with soap or ash after using a toilet and before handling food or eating is also recommended for cholera prevention by WHO Africa. File:Unsafe disposal of faecal sludge or sewage in Haiti (6458176073).jpg, Dumping of
sewage Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater Wastewater is generated after the use of fresh water Water (chemical formula H2O) is an inorganic, transparent, tasteless, odorless, and n ...
or Fecal sludge management, fecal sludge from a UN camp into a lake in the surroundings of Port-au-Prince is thought to have contributed to the spread of 2010 Haiti cholera outbreak, cholera after the Haiti earthquake in 2010, killing thousands. File:A SOIL EkoLakay toilet customer. (15921409131).jpg, Example of a urine-diverting dry toilet in a cholera-affected area in Haiti. This type of toilet stops transmission of disease via the Fecal–oral route, fecal-oral route due to water pollution. File:Cholera hospital in Dhaka.jpg, International Centre for Diarrhoeal Disease Research, Bangladesh, Cholera hospital in Dhaka, showing typical "cholera beds".


Surveillance

Surveillance and prompt reporting allow for containing cholera epidemics rapidly. Cholera exists as a seasonal disease in many endemic countries, occurring annually mostly during Wet season, 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 provides guidance for improving cholera control activities for the most vulnerable. For prevention to be effective, it is important that cases be reported to national health authorities.


Vaccination

Spanish physician Jaume Ferran i Clua developed a cholera inoculation in 1885, the first to immunize humans against a bacterial disease. However, his vaccine and inoculation was rather controversial and was rejected by his peers and several investigation commissions. Russian-Jewish bacteriologist Waldemar Haffkine successfully developed the first human cholera vaccine in July 1892. He conducted a massive inoculation program in British India. A number of safe and effective oral vaccines for cholera are available. 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. 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 endemic countries. The vaccine that the Food and Drug Administration, US Food and Drug Administration (FDA) recommends, Vaxchora, is an Cholera vaccine#Oral, oral attenuated live vaccine, that is effective as a single dose. 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. However, , it has limited availability. Work is under way to investigate the role of mass vaccination. The WHO recommends immunization of high-risk groups, such as children and people with HIV, in countries where this disease is Endemism, endemic. If people are immunized broadly, herd immunity results, with a decrease in the amount of contamination in the environment. WHO recommends that oral cholera vaccination be considered in areas where the disease is endemic (with seasonal peaks), as part of the response to outbreaks, or in a humanitarian crisis during which the risk of cholera is high. Oral Cholera Vaccine (OCV) has been recognized as an adjunct tool for prevention and control of cholera. The World Health Organization (WHO) has prequalified three bivalent cholera vaccines—Dukoral (SBL Vaccines), containing a non-toxic B-subunit of cholera toxin and providing protection against V. cholerae O1; and two vaccines developed using the same transfer of technology—ShanChol (Shantha Biotec) and Euvichol (EuBiologics Co.), which have bivalent O1 and O139 oral killed cholera vaccines. Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists.


Sari filtration

Developed for use in Bangladesh, the "sari filter" is a simple and cost-effective appropriate technology method for reducing the contamination of drinking water. Used sari cloth is preferable but other types of used cloth can be used with some effect, though the effectiveness will vary significantly. Used cloth is more effective than new cloth, as the repeated washing reduces the space between the fibers. Water collected in this way has a greatly reduced pathogen count—though it will not necessarily be perfectly safe, it is an improvement for poor people with limited options. In Bangladesh this practice was found to decrease rates of cholera by nearly half. It involves folding a ''sari'' four to eight times. Between uses the cloth should be rinsed in clean water and dried in the sun to kill any bacteria on it. A nylon cloth appears to work as well but is not as affordable.


Treatment

Continued eating speeds the recovery of normal intestinal function. The WHO recommends this generally for cases of diarrhea no matter what the underlying cause. 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."


Fluids

The most common error in caring for patients with cholera is to underestimate the speed and volume of fluids required. In most cases, cholera can be successfully treated with
oral rehydration therapy Oral rehydration therapy (ORT) is a type of fluid replacement used to prevent and treat dehydration, especially due to diarrhea. It involves drinking water with modest amounts of sugar and salts, specifically sodium and potassium. Oral rehydratio ...
(ORT), which is highly effective, safe, and simple to administer. Rice-based solutions are preferred to glucose-based ones due to greater efficiency. In severe cases with significant dehydration, intravenous rehydration may be necessary.
Ringer's lactate Ringer's lactate solution (RL), also known as sodium lactate solution and Hartmann's solution, is a mixture of sodium chloride Sodium chloride , commonly known as salt (although sea salt also contains other chemical salt (chemistry), salts), ...
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. This method was first tried on a mass scale during the Bangladesh Liberation War, and was found to have much success. 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. 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, 1/2 teaspoon of salt, 6 teaspoons of sugar, and added mashed banana for potassium and to improve taste.


Electrolytes

As there frequently is initially
acidosis Acidosis is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describes th ...

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. This may be done by consuming foods high in potassium, like bananas or coconut water.


Antibiotics

Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms. Use of antibiotics also reduces fluid requirements. People will recover without them, however, if sufficient hydration is maintained. The WHO only recommends antibiotics in those with severe dehydration. Doxycycline is typically used first line, although some Strain (biology), strains of ''V. cholerae'' have shown Antibiotic resistance, resistance. Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics proven to be effective include cotrimoxazole, erythromycin, tetracycline, chloramphenicol, and furazolidone. Fluoroquinolones, such as ciprofloxacin, also may be used, but resistance has been reported. Antibiotics improve outcomes in those who are both severely and not severely dehydrated. Azithromycin and tetracycline may work better than doxycycline or ciprofloxacin.


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%. Supplementation appears to be also effective in both treating and preventing infectious diarrhea due to other causes among children in the developing world.


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 Haiti cholera outbreak, 2010 epidemic in Haiti and the 2004 outbreak in India, death can occur within two hours of becoming ill.


Epidemiology

Cholera affects an estimated 2.8 million people worldwide, and causes approximately 95,000 deaths a year (uncertainty range: 21,000-143,000) . This occurs mainly in the developing world. In the early 1980s, death rates are believed to have been greater than three 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. In October 2016, an 2017 Yemen cholera outbreak, outbreak of cholera began in war-ravaged Yemen. WHO called it "the worst cholera outbreak in the world". Recent major outbreaks are the 2010s Haiti cholera outbreak and the 2016–2021 Yemen cholera outbreak. In 2019, 93% of the reported 923,037 cholera cases were from Yemen (with 1911 deaths reported). Between September 2019 and September 2020, a global total of over 450,000 cases and over 900 deaths was reported; however these numbers suffer from over-reporting from countries that report suspected cases (and not laboratory confirmed cases) as well as under-reporting from countries that do not report official cases (such as Bangladesh, India and Philippines). 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 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 Natural reservoir, 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. After the end of the 2010s Haiti cholera outbreak, there have not been any cholera cases in the Americas since February 2019. the disease is endemic in Africa and some areas of Asia (Bangladesh, India and Yemen). Cholera is not endemic in Europe, all reported cases had a travel history to endemic areas.


History of outbreaks

The word cholera is from el, 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. The disease appears in the European literature as early as 1642, from the Dutch physician Jacobus Bontius, Jakob de Bondt's description it in his De Medicina Indorum. (The "Indorum" of the title refers to the East Indies. He also gave first European descriptions of other diseases.) 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 stagnant water, still water, both of which provide ideal conditions for cholera to thrive. 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, (hence the name "Asiatic cholera"). Seven cholera pandemics have occurred in the past 200 years, with the seventh
pandemic A pandemic (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is approx ...

pandemic
originating in Indonesia in 1961. 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. 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. The Second cholera pandemic, 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. The Third cholera pandemic, 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 cholera pandemic, fourth pandemic lasted from 1863 to 1875 spread from India to Naples and Spain. The Fifth cholera pandemic, fifth pandemic was from 1881–1896 and started in India and spread to Europe, Asia, and South America. The Sixth cholera pandemic, 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 (primarily the city of Hamburg where more than 8.600 people died) and Naples from 1910–1911, also experienced severe outbreaks. The Seventh cholera pandemic, seventh pandemic originated in 1961 in Indonesia and is marked by the emergence of a new strain, nicknamed ''El Tor'', which still persists () in developing countries. Cholera became widespread in the 19th century. Since then it has killed tens of millions of people. In Russian Empire, Russia alone, between 1847 and 1851, more than one million people perished of the disease. It killed 150,000 Americans during the second pandemic. Between 1900 and 1920, perhaps eight million people died of cholera in India. Cholera became the first reportable disease in the United States due to the significant effects it had on health.
John Snow John Snow (15 March 1813 – 16 June 1858) was an English physician and a leader in the development of anaesthesia and medical hygiene. He is considered one of the founders of modern epidemiology, in part because of his work in tracing the s ...
, in England, was the first to identify the importance of contaminated water as its cause in 1854. Cholera is now no longer considered a pressing health threat in Europe and North America due to water filtration, filtering and Water chlorination, 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. 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. In the 1854–1855 outbreak in Naples homeopathic camphor was used according to Samuel Hahnemann, Hahnemann. 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. The first effective human vaccine was developed in 1885, and the first effective antibiotic was developed in 1948. Cholera cases are much less frequent in developed countries where governments have helped to establish water sanitation practices and effective medical treatments. The United States, for example, used to 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 choleraes spread through interior waterways like the Erie Canal and routes along the East Coast of the United States, Eastern Seaboard. 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, so cholera was able to spread. Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically cholera. File:Cholera.jpg, Drawing of Death (personification), Death bringing cholera, in ''Le Petit Journal (newspaper), Le Petit Journal'' (1912). File:Pedro II of Brazil and ministers of state.JPG, Emperor Pedro II of Brazil visiting people with cholera in 1855. File:Cholera 395.1.jpg, Hand bill from the Metropolitan Board of Health, 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.


Research

One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist
John Snow John Snow (15 March 1813 – 16 June 1858) was an English physician and a leader in the development of anaesthesia and medical hygiene. He is considered one of the founders of modern epidemiology, in part because of his work in tracing the s ...
(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. 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 Sewage (or domestic sewage, domestic wastewater, municipal wastewater) is a type of wastewater Wastewater is generated after the use of fresh water Water (chemical formula H2O) is an inorganic, transparent, tasteless, odorless, and n ...
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 30 years or so. For his work on cholera, John Snow is often regarded as the "Father of Epidemiology". The bacterium was isolated in 1854 by Italian anatomist Filippo Pacini, but its exact nature and his results were not widely known. In the same year, the Catalonia, Catalan Joaquim Balcells i Pascual discovered the bacterium and in 1856 probably António Augusto da Costa Simões and José Ferreira de Macedo Pinto, two Portuguese men, did the same. Cities in developed nations made massive investment in clean water supply and well-separated sewage treatment infrastructures between the mid-1850s and the 1900s. This eliminated the threat of cholera epidemics from the major developed cities in the world. In 1883, Robert Koch identified ''V. cholerae'' with a microscope as the bacillus causing the disease. Hemendra Nath Chatterjee, a Bengali scientist, who first formulated and demonstrated the effectiveness of oral rehydration salt (ORS) for
diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery defecation, bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration of ...
. In his 1953 paper, published in The Lancet, he states that promethazine can stop
vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach The stomach is a muscular, in the of humans and many other animals, including several s. The stomach has a dilat ...

vomiting
during cholera and then oral rehydration is possible. The formulation of the fluid replacement solution was 4 g of sodium chloride, 25 g of glucose and 1000 ml of water. Indian people, Indian medical scientist Sambhu Nath De discovered the
cholera toxin Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex is a protein complex functioning as a molecular biological machine. It uses protein domain dynamics on nanoscales A protei ...

cholera toxin
, the ''animal model of cholera'', and successfully demonstrate the method of transmission of cholera pathogen ''Vibrio cholerae''. 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. More recently, in 2002, Alam, ''et al.'', studied stool samples from patients at the International Centre for Diarrhoeal Disease Research, Bangladesh, International Centre for Diarrhoeal Disease 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 the bacterium creates a hyperinfected 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.


Global Strategy

In 2017, the WHO launched the "Ending Cholera: a global roadmap to 2030" strategy which aims to reduce cholera deaths by 90% by 2030. The strategy was developed by the Global Task Force on Cholera Control (GTFCC) which develops country-specific plans and monitors progress. The approach to achieve this goal combines surveillance, water sanitation, treatment and oral vaccines. Specifically, the control strategy focusses on three approaches: i) early detection and response to outbreaks to contain outbreaks, ii) stopping cholera transmission through improved sanitation and vaccines in hotspots, and iii) a global framework for cholera control through the GTFCC. The WHO and the GTFCC do not consider global cholera eradication a viable goal. Even though humans are the only host of cholera, the bacterium can persist in the environment without a human host. While global eradication is not possible, elimination of human to human transmission may be possible; and local elimination is possible, most recently during the 2010s Haiti cholera outbreak which aims to achieve certification of elimination by 2022. The GTFCC targets 47 countries, 13 of which have established vaccination campaigns.


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. 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. The Haitian government's inability to provide safe drinking water after the 2010 earthquake led to an increase in cholera cases as well. Similarly, South Africa's cholera outbreak was exacerbated by the government's policy of privatizing water programs. The wealthy elite of the country were able to afford safe water while others had to use water from cholera-infected rivers. According to Rita R. Colwell of the James Baker Institute, if cholera does begin to spread, government preparedness is crucial. A government's ability to contain the disease before it extends to other areas can prevent a high death toll and the development of an epidemic or even pandemic. Effective disease surveillance can ensure that cholera outbreaks are recognized as soon as possible and dealt with appropriately. Oftentimes, this will allow public health programs to determine and control the cause of the cases, whether it is unsanitary water or seafood that have accumulated a lot of ''Vibrio cholerae'' specimens. Having an effective surveillance program contributes to a government's ability to prevent cholera from spreading. In the year 2000 in the state of Kerala in India, the Kottayam district was determined to be "Cholera-affected"; this pronouncement led to task forces that concentrated on educating citizens with 13,670 information sessions about human health. These task forces promoted the boiling of water to obtain safe water, and provided chlorine and oral rehydration salts. Ultimately, this helped to control the spread of the disease to other areas and minimize deaths. On the other hand, researchers have shown that most of the citizens infected during the 1991 cholera outbreak in Bangladesh lived in rural areas, and were not recognized by the government's surveillance program. This inhibited physicians' abilities to detect cholera cases early. 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. 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. The speed with which government leaders respond to cholera outbreaks is important. Besides contributing to an effective or declining public health care system and water sanitation treatments, government can have indirect effects on cholera control and the effectiveness of a response to cholera. A country's government can impact its ability to prevent disease and control its spread. A speedy government response backed by a fully functioning health care system and financial resources can prevent cholera's spread. This limits cholera's ability to cause death, or at the very least a decline in education, as children are kept out of school to minimize the risk of infection.


Notable cases

* Pyotr Ilyich Tchaikovsky, Tchaikovsky's death has traditionally been attributed to cholera, most probably contracted through drinking contaminated water several days earlier. Tchaikovsky's mother died of cholera, and his father became sick with cholera at this time but made a full recovery. Some scholars, however, including English musicologist and Tchaikovsky authority David Brown (musicologist), David Brown and biographer Anthony Holden, have theorized that his death was a suicide. * 2010 Haiti cholera outbreak. Ten months after the 2010 earthquake, an 2010 Haiti cholera outbreak, outbreak swept over Haiti, traced to a United Nations base of Peacekeeping, peacekeepers from Nepal. This marks the worst cholera outbreak in recent history, as well as the best documented cholera outbreak in modern public health. * Adam Mickiewicz, Polish poet and novelist, is thought to have died of cholera in Istanbul in 1855. * Nicolas Léonard Sadi Carnot, Sadi Carnot, Physicist, a founder of thermodynamics (d. 1832) * Charles X of France, Charles X, King of France (d. 1836) * James K. Polk, eleventh president of the United States (d. 1849) * Carl von Clausewitz, Prussian soldier and German military theorist (d. 1831) * Elliot Bovill, Chief Justice of Singapore, Chief Justice of the Straits Settlements (1893) *Nikola Tesla, Serbian-American inventor, engineer and futurist known for his contributions to the design of the modern alternating current (AC) electricity supply system, contracted cholera in 1873 at the age of 17. He was bedridden for nine months, and near death multiple times, but survived and fully recovered.


In popular culture

Unlike tuberculosis ("consumption") which in literature and the arts was often romanticized as a disease of denizens of the demimondaine, demimonde or those with an artistic temperament, cholera is a disease which almost entirely affects the lower-classes living in filth and poverty. This, and the unpleasant course of the disease – which includes voluminous "rice-water" diarrhea, the hemorrhaging of liquids from the mouth, and violent muscle contractions which continue even after death – has discouraged the disease from being romanticized, or even the actual factual presentation of the disease in popular culture. * The 1889 novel ''Mastro-don Gesualdo'' by Giovanni Verga presents the course of a cholera epidemic across the island of Sicily, but does not show the suffering of the victims. * In Thomas Mann's novella ''Death in Venice'', first published in 1912 as ''Der Tod in Venedig'', Mann "presented the disease as emblematic of the final 'bestial degradation' of the sexually transgressive author Gustav von Aschenbach." Contrary to the actual facts of how violently cholera kills, Mann has his protagonist die peacefully on a beach in a deck chair. Luchino Visconti's Death in Venice (film), 1971 film version also hid from the audience the actual course of the disease. Mann's novella was also Death in Venice (opera), made into an opera by Benjamin Britten in 1973, his last one, and into a ballet by John Neumeier for his Hamburg Ballet company, in December 2003.* * In Gabriel Garcia Márquez's 1985 novel ''Love in the Time of Cholera'', cholera is "a looming background presence rather than a central figure requiring vile description." The novel was adapted in 2007 for the Love in the Time of Cholera (film), film of the same name directed by Mike Newell (director), Mike Newell.


Country examples


Zambia

In Zambia, widespread cholera outbreaks have occurred since 1977, most commonly in the capital city of Lusaka. In 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of ''
Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative Gram-negative bacteria are bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large domain (biology), domain o ...

Vibrio cholerae
'' O1, biotype El Tor, serotype Ogawa, from stool samples from two patients with acute watery diarrhea. There was a rapid increase in the number of cases from several hundred cases in early December 2017 to approximately 2,000 by early January 2018. With intensification of the rains, new cases increased on a daily basis reaching a peak on the first week of January 2018 with over 700 cases reported. In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. The Zambian Ministry of Health implemented a reactive one-dose Oral Cholera Vaccine (OCV) campaign in April 2016 in three Lusaka compounds, followed by a pre-emptive second-round in December.


India

In India, Kolkata city in West Bengal state in the Ganges delta has been described as the "homeland of cholera", with regular outbreaks and pronounced seasonality. In India, where the disease is endemic, cholera outbreaks occur every year between dry seasons (March–April) and rainy seasons (September–October). India is also characterized by high population density, unsafe drinking water, open drains, and poor sanitation which provide an optimal niche for survival, sustenance and transmission of ''Vibrio cholerae''.


Democratic Republic of Congo

In Goma in the Democratic Republic of Congo, cholera has left an enduring mark on human and medical history. Cholera pandemics in the 19th and 20th centuries led to the growth of epidemiology as a science and in recent years it has continued to press advances in the concepts of disease ecology, basic membrane biology, and transmembrane signaling and in the use of scientific information and treatment design.


Notes


References


Further reading

* * * Bilson, Geoffrey. ''A Darkened House: Cholera in Nineteenth-Century Canada'' (U of Toronto Press, 1980). * * * * * Gilbert, Pamela K. ''Cholera and Nation: Doctoring the Social Body in Victorian England" (SUNY Press, 2008). * * * * * * * * * * * Snowden, Frank M. ''Naples in the Time of Cholera, 1884-1911'' (Cambridge UP, 1995). * Vinten-Johansen, Peter, ed. ''Investigating Cholera in Broad Street: A History in Documents'' (Broadview Press, 2020). regarding 1850s in England. * Vinten-Johansen, Peter, et al. ''Cholera, chloroform, and the science of medicine: a life of John Snow'' (2003).


External links


Prevention and control of cholera outbreaks: WHO policy and recommendations

Cholera
World Health Organization
Cholera – ''Vibrio cholerae'' infection
Centers for Disease Control and Prevention * {{Authority control Cholera, Diarrhea Foodborne illnesses Gastrointestinal tract disorders Intestinal infectious diseases Neglected tropical diseases Tropical diseases Epidemics Pandemics Wikipedia medicine articles ready to translate Wikipedia emergency medicine articles ready to translate Sanitation Waterborne diseases Vaccine-preventable diseases