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Cholera

Cholera

Overview
Cholera is an infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

 of the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

 that is caused by the bacterium Vibrio cholerae
Vibrio cholerae
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultatively anaerobic and has a flagella at one cell pole. V...

. The main symptoms are profuse watery diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

 and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces of an infected but asymptomatic person. The severity of the diarrhea and vomiting can lead to rapid dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...

 and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 imbalance and death in some cases.
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Encyclopedia
Cholera is an infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

 of the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

 that is caused by the bacterium Vibrio cholerae
Vibrio cholerae
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultatively anaerobic and has a flagella at one cell pole. V...

. The main symptoms are profuse watery diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

 and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces of an infected but asymptomatic person. The severity of the diarrhea and vomiting can lead to rapid dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...

 and electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

 imbalance and death in some cases. The primary treatment is with oral rehydration solution (ORS) to replace water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

 and electrolytes
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....

, and if this is not tolerated or doesn't provides quick enough treatment, intravenous fluids can also be used. Antibiotics are beneficial in those with severe disease to shorten the duration and severity. Worldwide it affects 3–5 million people and causes 100,000–130,000 deaths a year . Cholera was one of the earliest infections to be studied by epidemiological
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...

 methods.

Signs and symptoms



The primary symptoms of cholera are profuse painless diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

 and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

 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 litre
Litre
pic|200px|right|thumb|One litre is equivalent to this cubeEach side is 10 cm1 litre water = 1 kilogram water The litre is a metric system unit of volume equal to 1 cubic decimetre , to 1,000 cubic centimetres , and to 1/1,000 cubic metre...

s of diarrhea a day with fatal results. 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 life-threatening dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...

 and electrolyte imbalances. The typical symptoms of dehydration include low blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

, poor skin
turgor (wrinkled hands), sunken eyes, and a rapid pulse.

Cause





Transmission is primarily due to the fecal contamination of food and water due to poor sanitation
Sanitation
Sanitation is the hygienic means of promoting health through prevention of human contact with the hazards of wastes. Hazards can be either physical, microbiological, biological or chemical agents of disease. Wastes that can cause health problems are human and animal feces, solid wastes, domestic...

. This bacterium can, however, live naturally in any environment.

Susceptibility


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 acid
Gastric acid
Gastric acid is a digestive fluid, formed in the stomach. It has a pH of 1 to 2 and is composed of hydrochloric acid , and large quantities of potassium chloride and sodium chloride...

ity (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
Blood type
A blood type is a classification of blood based on the presence or absence of inherited antigenic substances on the surface of red blood cells . These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system...

, with those with type O blood being the most susceptible. Persons with lower immunity such as persons with AIDS or children who are malnourished are more likely to experience a severe case if they become infected. However, it should be noted that any particular person, even a healthy adult in middle age, can experience a severe case, and each particular person's case should be measured by their particular loss of fluids, preferably in consultation with a doctor or other health worker.

It has been said that cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...

 genetic mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...

 in humans has maintained 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
Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes...

 channel proteins interferes with bacteria binding to the gastrointestinal epithelium, thus reducing the effects of an infection.

Transmission


Cholera 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
Shellfish
Shellfish is a culinary and fisheries term for exoskeleton-bearing aquatic invertebrates used as food, including various species of molluscs, crustaceans, and echinoderms. Although most kinds of shellfish are harvested from saltwater environments, some kinds are found only in freshwater...

 and plankton
Plankton
Plankton are any drifting organisms that inhabit the pelagic zone of oceans, seas, or bodies of fresh water. That is, plankton are defined by their ecological niche rather than phylogenetic or taxonomic classification...

.

People infected with cholera often have diarrhea, and if this highly liquid stool, colloquially referred to as "rice-water," or "faucet butt," contaminates water used by others, disease transmission may occur. The source of the contamination is typically other cholera sufferers when their untreated diarrheal discharge is allowed to get into waterways or into groundwater
Groundwater
Groundwater is water located beneath the ground surface in soil pore spaces and in the fractures of rock formations. A unit of rock or an unconsolidated deposit is called an aquifer when it can yield a usable quantity of water. The depth at which soil pore spaces or fractures and voids in rock...

 or drinking water supplies. Drinking any infected water and eating any foods washed in the water, as well as shellfish
Shellfish
Shellfish is a culinary and fisheries term for exoskeleton-bearing aquatic invertebrates used as food, including various species of molluscs, crustaceans, and echinoderms. Although most kinds of shellfish are harvested from saltwater environments, some kinds are found only in freshwater...

 living in the affected waterway
Waterway
A waterway is any navigable body of water. Waterways can include rivers, lakes, seas, oceans, and canals. In order for a waterway to be navigable, it must meet several criteria:...

, can cause a person to contract an infection. Cholera is rarely spread directly from person to person. Both toxic and nontoxic strains exist. Nontoxic strains can acquire toxicity through a temperate bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...

. Coastal cholera outbreaks typically follow zooplankton blooms
Algal bloom
An algal bloom is a rapid increase or accumulation in the population of algae in an aquatic system. Algal blooms may occur in freshwater as well as marine environments. Typically, only one or a small number of phytoplankton species are involved, and some blooms may be recognized by discoloration...

, thus making cholera a zoonotic
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...

 disease.

Mechanism


Most bacteria, when consumed, do not survive the acidic conditions of the human stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...

. The few bacteria that do survive conserve their energy and stored nutrients
Nutrient
A nutrient is a chemical that an organism needs to live and grow or a substance used in an organism's metabolism which must be taken in from its environment. They are used to build and repair tissues, regulate body processes and are converted to and used as energy...

 during the passage through the stomach by shutting down much protein production. When the surviving bacteria exit the stomach and reach the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...

, they need to propel themselves through the thick mucus
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

 that lines the small intestine to get to the intestinal walls, where they can thrive. V. cholerae bacteria start up production of the hollow cylindrical protein flagellin
Flagellin
Flagellin is a protein that arranges itself in a hollow cylinder to form the filament in bacterial flagellum. It has a mass of about 30,000 to 60,000 daltons...

 to make flagella, the cork-screw helical fibers they rotate to propel themselves through the mucus of the small intestine.

Once the cholera bacteria reach the intestinal wall, they no longer need the flagella propellers to move. 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
Cholera toxin
Cholera toxin is a protein complex secreted by the bacterium Vibrio cholerae. CTX is responsible for the massive, watery diarrhea characteristic of cholera infection.- Structure :...

 (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
GM1
GM1 the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain...

 ganglioside
Ganglioside
Ganglioside is a molecule composed of a glycosphingolipid with one or more sialic acids linked on the sugar chain. The 60+ known gangliosides differ mainly in the position and number of NANA residues.It is a component of the cell plasma membrane that modulates cell signal transduction events...

s on the surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates
ADP-ribosylation
ADP-ribosylation is the addition of one or more ADP-ribose moieties to a protein. These reactions are involved in cell signaling and the control of many cell processes, including DNA repair and apoptosis.-ADP-ribosylation enzymes:...

 G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...

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. 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
Gs alpha subunit
The Gs alpha subunit is a heterotrimeric G protein subunit that activates the cAMP-dependent pathway by activating adenylate cyclase.-Receptors:The G protein-coupled receptors that couple to this kind of G-protein include:...

 of the heterotrimeric G protein
Heterotrimeric G protein
"G protein" usually refers to the membrane-associated heterotrimeric G proteins, sometimes referred to as the "large" G proteins. These proteins are activated by G protein-coupled receptors and are made up of alpha , beta and gamma subunits, the latter two referred to as the beta-gamma...

. This results in constitutive cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...

 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 temperate bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...

 called CTXf or CTXφ.

Microbiologists have studied the genetic mechanisms
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...

 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
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...

 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 litres 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
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

 layers, and intestinal wall. Researchers have discovered there is a complex cascade of regulatory proteins that control expression of V. cholerae virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 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
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 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 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.

Diagnosis


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. In epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...

 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.

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
Vibrio cholerae
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultatively anaerobic and has a flagella at one cell pole. V...

O1. If V. cholerae serogroup
Serotype
Serotype or serovar refers to distinct variations within a subspecies of bacteria or viruses. These microorganisms, viruses, or cells are classified together based on their cell surface antigens...

 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

  1. Alkaline peptone water at pH 8.6
  2. Monsur's taurocholate tellurite peptone water at pH 9.2

Plating media

  1. Alkaline bile salt agar (BSA): The colonies are very similar to those on nutrient agar
    Agar
    Agar or agar-agar is a gelatinous substance derived from a polysaccharide that accumulates in the cell walls of agarophyte red algae. Throughout history into modern times, agar has been chiefly used as an ingredient in desserts throughout Asia and also as a solid substrate to contain culture medium...

    .
  2. Monsur's gelatin Tauro cholate trypticase tellurite agar (GTTA) medium: Cholera vibrios produce small translucent colonies with a greyish black center.
  3. TCBS medium: This the mostly widely used medium; it contains thiosulphate, citrate, bile salts and sucrose. Cholera vibrios produce flat 2–3 mm in diameter, yellow nucleated colonies.


Direct microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...

 of stool is not recommended, as it is unreliable. Microscopy is preferred only after enrichment, as this process reveals the characteristic motility of Vibrio and its inhibition by appropriate antisera
Antiserum
Antiserum is blood serum containing polyclonal antibodies. Antiserum is used to pass on passive immunity to many diseases. Passive antibody transfusion from a previous human survivor is the only known effective treatment for Ebola infection .The most common use of antiserum in humans is as...

. Diagnosis can be confirmed, as well, as serotyping done by agglutination
Agglutination (biology)
Agglutination is the clumping of particles. The word agglutination comes from the Latin agglutinare, meaning "to glue."This occurs in biology in three main examples:...

 with specific sera.

Prevention



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
Water treatment
Water treatment describes those processes used to make water more acceptable for a desired end-use. These can include use as drinking water, industrial processes, medical and many other uses. The goal of all water treatment process is to remove existing contaminants in the water, or reduce the...

 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 fecal 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
    Sterilization (microbiology)
    Sterilization is a term referring to any process that eliminates or kills all forms of microbial life, including transmissible agents present on a surface, contained in a fluid, in medication, or in a compound such as biological culture media...

     by washing in hot water, using chlorine
    Chlorine
    Chlorine is the chemical element with atomic number 17 and symbol Cl. It is the second lightest halogen, found in the periodic table in group 17. The element forms diatomic molecules under standard conditions, called dichlorine...

     bleach
    Bleach
    Bleach refers to a number of chemicals that remove color, whiten, or disinfect, often via oxidation. Common chemical bleaches include household chlorine bleach , lye, oxygen bleach , and bleaching powder...

     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: antibacterial treatment of general sewage
    Sewage
    Sewage is water-carried waste, in solution or suspension, that is intended to be removed from a community. Also known as wastewater, it is more than 99% water and is characterized by volume or rate of flow, physical condition, chemical constituents and the bacteriological organisms that it contains...

     by chlorine, ozone, ultraviolet 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
    Decontamination
    Decontamination is the process of cleansing the human body to remove contamination by hazardous materials including chemicals, radioactive substances, and infectious material...

     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
    Chlorination
    Chlorination is the process of adding the element chlorine to water as a method of water purification to make it fit for human consumption as drinking water...

    , ozone water treatment, ultraviolet light sterilization (e.g. by solar water disinfection
    Solar water disinfection
    Solar water disinfection, also known as SODIS is a method of disinfecting water using only sunlight and plastic PET bottles. SODIS is a free and effective method for decentralized water treatment, usually applied at the household level and is recommended by the World Health Organization as a viable...

    ), 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 filter
    Cloth filter
    Developed for use in Bangladesh, the cloth filter is a simple and cost-effective appropriate technology method for reducing the contamination of drinking water...

    s, though very basic, have significantly reduced the occurrence of cholera when used in poor villages in Bangladesh
    Bangladesh
    Bangladesh , officially the People's Republic of Bangladesh is a sovereign state located in South Asia. It is bordered by India on all sides except for a small border with Burma to the far southeast and by the Bay of Bengal to the south...

     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.

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 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.

Vaccine


A number of safe and effective oral vaccines for cholera are available. 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
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

 (CDC) for most people traveling from the United States to endemic countries. One injectable vaccine was found to be effective for two to three years. The protective efficacy was 28% lower in children less than 5 years old. However, as of 2010, it has limited availability. 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
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

, in countries where this disease is endemic. If people are immunized broadly, herd immunity
Herd immunity
Herd immunity describes a form of immunity that occurs when the vaccination of a significant portion of a population provides a measure of protection for individuals who have not developed immunity...

 results, with a decrease in the amount of contamination in the environment.

Treatment



Continued eating speeds the recovery of normal intestinal function. The World Health Organization recommends this generally for cases of diarrhea from whatever 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


In most cases, cholera can be successfully treated with oral rehydration therapy
Oral rehydration therapy
Oral rehydration therapy is a simple treatment for dehydration associated with diarrhoea, particularly gastroenteritis or gastroenteropathy, such as that caused by cholera or rotavirus. ORT consists of a solution of salts and sugars which is taken by mouth...

 (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 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
Bangladesh Liberation War
The Bangladesh Liberation War was an armed conflict pitting East Pakistan and India against West Pakistan. The war resulted in the secession of East Pakistan, which became the independent nation of Bangladesh....

, and was found to have much success.

If commercially produced oral rehydration solutions are too expensive or difficult to obtain, solutions can be made. One such recipe calls for 1 litre 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
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....

, the potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 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


Antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

 treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms. People will recover without them, however, if sufficient hydration is maintained. Doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

 is typically used first line, although some strains
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

 of V. cholerae have shown resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

. Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics that have been proven effective include cotrimoxazole, erythromycin
Erythromycin
Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...

, tetracycline, chloramphenicol
Chloramphenicol
Chloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...

, and furazolidone
Furazolidone
Furazolidone is a nitrofuran antibacterial. It is marketed by Roberts Laboratories under the brand name Furoxone and by GlaxoSmithKline as Dependal-M.-Uses:It is used to treat diarrhoea and enteritis caused by bacteria or protozoan infections....

. Fluoroquinolones, such as norfloxacin
Norfloxacin
Norfloxacin is a synthetic chemotherapeutic antibacterial agent occasionally used to treat common as well as complicated urinary tract infections. It is sold under various brand names with the most common being Noroxin. In form of ophthalmic solutions it is known as Chibroxin...

, also may be used, but resistance has been reported.

In many areas of the world, antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 is increasing. In Bangladesh
Bangladesh
Bangladesh , officially the People's Republic of Bangladesh is a sovereign state located in South Asia. It is bordered by India on all sides except for a small border with Burma to the far southeast and by the Bay of Bengal to the south...

, for example, most cases are resistant to tetracycline, trimethoprim-sulfamethoxazole, and erythromycin. Rapid diagnostic assay methods are available for the identification of multiple drug-resistant cases. New generation antimicrobials have been discovered which are effective against in in vitro studies.

Sari Filtration


An effective and relatively cheap method to prevent transmission of V. cholera is the use of folding Saris multiple times to create a simple filter. Folding Saris four to eight times may create a simple filter to reduce the amount of active V. cholera in the filtered water..
The education of proper sari filter use is imperative as there is a positive correlation and soiled saris worn by women are vectors of transmission of enteric pathogens to young children. Educating at risk populations about the proper use of the Sari filter may decrease V. cholera associated disease.

Prognosis


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

Epidemiology




It is estimated that cholera affects 3-5 million people worldwide, and causes 100,000-130,000 deaths a year as of 2010. This occurs mainly in the developing world. In the early 1980s, death rates are believed to have been greater than 3 million a year. It is difficult to calculate exact numbers of cases, as many go unreported due to concerns that an outbreak may have a negative impact on the tourism of a country. Cholera remains both epidemic
Epidemic
In epidemiology, an epidemic , occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience...

 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
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...

 and lack of treatment of drinking water greatly facilitate its spread, but bodies of water can serve as a reservoir
Natural reservoir
Natural reservoir or nidus, refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic and non-lethal...

, and seafood shipped long distances can spread the disease. Cholera was not known in the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...

 for most of the 20th century, but it reappeared towards the end of that century and seems likely to persist.

History


The word cholera is from kholera from χολή kholē "bile". Cholera likely has its origins in the Indian subcontinent
Indian subcontinent
The Indian subcontinent, also Indian Subcontinent, Indo-Pak Subcontinent or South Asian Subcontinent is a region of the Asian continent on the Indian tectonic plate from the Hindu Kush or Hindu Koh, Himalayas and including the Kuen Lun and Karakoram ranges, forming a land mass which extends...

; it has been prevalent in the Ganges delta
Ganges Delta
The Ganges Delta is a river delta in the South Asia region of Bengal, consisting of Bangladesh and the state of West Bengal, India. It is the world's largest delta, and empties into the Bay of Bengal...

 since ancient times. The disease first spread by trade routes (land and sea) to Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...

 in 1817, then to Western Europe
Western Europe
Western Europe is a loose term for the collection of countries in the western most region of the European continents, though this definition is context-dependent and carries cultural and political connotations. One definition describes Western Europe as a geographic entity—the region lying in the...

, and from Europe to North America
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...

. There have been seven cholera pandemic
Pandemic
A pandemic is an epidemic of infectious disease that is spreading through human populations across a large region; for instance multiple continents, or even worldwide. A widespread endemic disease that is stable in terms of how many people are getting sick from it is not a pandemic...

s in the past 200 years, with the seventh originating in Indonesia
Indonesia
Indonesia , officially the Republic of Indonesia , is a country in Southeast Asia and Oceania. Indonesia is an archipelago comprising approximately 13,000 islands. It has 33 provinces with over 238 million people, and is the world's fourth most populous country. Indonesia is a republic, with an...

 in 1961.

From a local disease, cholera became one of the most widespread and deadly diseases of the 19th century, killing an estimated tens of millions of people. In Russia
Russian Empire
The Russian Empire was a state that existed from 1721 until the Russian Revolution of 1917. It was the successor to the Tsardom of Russia and the predecessor of the Soviet Union...

 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 (physician)
John Snow was an English physician and a leader in the adoption of anaesthesia and medical hygiene. He is considered to be one of the fathers of epidemiology, because of his work in tracing the source of a cholera outbreak in Soho, England, in 1854.-Early life and education:Snow was born 15 March...

, in 1854, was the first to identify the importance of contaminated water in its cause. Cholera is now no longer considered a pressing health threat in Europe and North America due to filtering and chlorination
Chlorination
Chlorination is the process of adding the element chlorine to water as a method of water purification to make it fit for human consumption as drinking water...

 of water supplies, but still heavily affects populations in developing countries.

In the past, people traveling in ships would hang a yellow quarantine
Quarantine
Quarantine is compulsory isolation, typically to contain the spread of something considered dangerous, often but not always disease. The word comes from the Italian quarantena, meaning forty-day period....

 flag if one or more of the crew members suffered from cholera. Passengers from 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
International maritime signal flags
The system of international maritime signal flags is one system of flag signals representing individual letters of the alphabet in signals to or from ships...

, the quarantine flag is yellow and black.

Cholera morbus


The term cholera morbus was used in the 19th and early 20th centuries to describe both nonepidemic 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
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...

.

Research


The Russian-born bacteriologist Waldemar Haffkine
Waldemar Haffkine
Waldemar Mordecai Wolff Haffkine, CIE was a Russian Jewish bacteriologist, whose career was blighted in Russia because "he refused to convert to Russian Orthodoxy." He emigrated and worked at the Pasteur Institute in Paris, where he developed an anti-cholera vaccine that he tried out successfully...

 developed the first cholera vaccine around 1900. The bacterium had been originally isolated forty five years earlier (1855) by Italian anatomist Filippo Pacini
Filippo Pacini
Filippo Pacini was an Italian anatomist, posthumously famous for isolating the cholera bacillus Vibrio cholerae in 1854, well before Robert Koch's more widely accepted discoveries thirty years later....

, but its exact nature and his results were not widely known.

One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist John Snow
John Snow (physician)
John Snow was an English physician and a leader in the adoption of anaesthesia and medical hygiene. He is considered to be one of the fathers of epidemiology, because of his work in tracing the source of a cholera outbreak in Soho, England, in 1854.-Early life and education:Snow was born 15 March...

 (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 etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....

 of the disease. In two pioneering epidemiological field studies, he was able to demonstrate human sewage
Sewage
Sewage is water-carried waste, in solution or suspension, that is intended to be removed from a community. Also known as wastewater, it is more than 99% water and is characterized by volume or rate of flow, physical condition, chemical constituents and the bacteriological organisms that it contains...

 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 between the mid-1850s and the 1900s. This eliminated the threat of cholera epidemics from the major developed cities in the world. In 1885, Robert Koch
Robert Koch
Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis , the Tuberculosis bacillus and the Vibrio cholerae and for his development of Koch's postulates....

 identified V. cholerae with a microscope as the bacillus causing the disease..

Cholera has been a laboratory for the study of evolution of virulence. The province of Bengal in British India
British Raj
British Raj was the British rule in the Indian subcontinent between 1858 and 1947; The term can also refer to the period of dominion...

 was partitioned into West Bengal
West Bengal
West Bengal is a state in the eastern region of India and is the nation's fourth-most populous. It is also the seventh-most populous sub-national entity in the world, with over 91 million inhabitants. A major agricultural producer, West Bengal is the sixth-largest contributor to India's GDP...

 and East Pakistan
East Pakistan
East Pakistan was a provincial state of Pakistan established in 14 August 1947. The provincial state existed until its declaration of independence on 26 March 1971 as the independent nation of Bangladesh. Pakistan recognized the new nation on 16 December 1971. East Pakistan was created from Bengal...

 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
Bangladesh
Bangladesh , officially the People's Republic of Bangladesh is a sovereign state located in South Asia. It is bordered by India on all sides except for a small border with Burma to the far southeast and by the Bay of Bengal to the south...

). As a consequence, 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 draw upon the resources of the host population and rapidly kill many victims.

More recently, in 2002, Alam, et al., studied stool samples from patients at the International Centre for Diarrhoeal Disease
International Centre for Diarrhoeal Disease Research, Bangladesh
The International Centre for Diarrhoeal Disease Research, Bangladesh is an international health research organization located in Dhaka, Bangladesh. Dedicated to saving lives through research and treatment, ICDDR,B addresses some of the most critical health concerns facing the world today, ranging...

 (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 the bacterium creates a hyperinfected state where gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s that control biosynthesis of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s, iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

 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.

Notable cases

  • Tchaikovsky
    Pyotr Ilyich Tchaikovsky
    Pyotr Ilyich Tchaikovsky Pyotr Ilyich Tchaikovsky Pyotr Ilyich Tchaikovsky (Russian: Пётр Ильи́ч Чайко́вский ; often "Peter Ilich Tchaikovsky" in English. His names are also transliterated "Piotr" or "Petr"; "Ilitsch", "Il'ich" or "Illyich"; and "Tschaikowski", "Tschaikowsky", "Chajkovskij"...

    '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 affecting St. Petersburg, such a connection is quite plausible ...." 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
    David Brown (musicologist)
    David Brown is an English musicologist, most noteworthy for his major study of Tchaikovsky’s life and works.Brown studied English, Latin and music at the University of Sheffield, graduating in 1951, and took his MusB there . During national service he studied Russian and was commissioned in the...

     and biographer Anthony Holden
    Anthony Holden
    Anthony Holden is an English writer, broadcaster and critic, particularly known as a biographer of artists including Shakespeare, Tchaikovsky, Leigh Hunt, Lorenzo da Ponte and Laurence Olivier, and of members of the British Royal family, notably Charles, Prince of Wales...

    , have theorized that his death was a suicide.


Other famous people believed to have died of cholera include:
  • Charles X
    Charles X of France
    Charles X was known for most of his life as the Comte d'Artois before he reigned as King of France and of Navarre from 16 September 1824 until 2 August 1830. A younger brother to Kings Louis XVI and Louis XVIII, he supported the latter in exile and eventually succeeded him...

    , King of France (d. 1836)
  • James K. Polk
    James K. Polk
    James Knox Polk was the 11th President of the United States . Polk was born in Mecklenburg County, North Carolina. He later lived in and represented Tennessee. A Democrat, Polk served as the 17th Speaker of the House of Representatives and the 12th Governor of Tennessee...

    , eleventh president of the United States (d. 1849)
  • Carl von Clausewitz
    Carl von Clausewitz
    Carl Philipp Gottfried von Clausewitz was a Prussian soldier and German military theorist who stressed the moral and political aspects of war...

    , Prussian soldier and German military theorist (d. 1831)
  • Elliott Frost, son of American poet Robert Frost
    Robert Frost
    Robert Lee Frost was an American poet. He is highly regarded for his realistic depictions of rural life and his command of American colloquial speech. His work frequently employed settings from rural life in New England in the early twentieth century, using them to examine complex social and...

     (d. 1900)

Further reading

  • Myron Echenberg: Africa in the Time of Cholera. A History of Pandemics from 1817 to the Present, Cambridge University Press, New York 2011 (Paperback) ISBN 978-0-521-18820-3

External links


  • Cholera - World Health Organization
    World Health Organization
    The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

  • The Attenuation of the Causal Agent of Fowl Cholera, by Louis Pasteur, 1880
  • What is Cholera? - Centers for Disease Control and Prevention
    Centers for Disease Control and Prevention
    The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...

  • Steven Shapin, "Sick City: Maps and mortality in the time of cholera", The New Yorker
    The New Yorker
    The New Yorker is an American magazine of reportage, commentary, criticism, essays, fiction, satire, cartoons and poetry published by Condé Nast...

     May 2006. A review of Steven Johnson, “The Ghost Map: The story of London’s most terrifying epidemic — and how it changed science, cities, and the modern world”
  • Cholera Epidemic in NYC in 1832 New York Times 15 April 2008
  • The Cholera Timebomb in The DRC - slideshow by The First Post
    The First Post
    The First Post is a British daily online news magazine based in London. It was launched in August 2005. It publishes news, current affairs, lifestyle, opinion, arts and sports pages, and it features an online games arcade and a cinema featuring short films, virals, trailers and eyewitness news...