Cholera

From DrugPedia: A Wikipedia for Drug discovery

Cholera, sometimes known as Asiatic cholera or epidemic cholera, is an infectious gastroenteritis caused by the bacterium Vibrio cholerae. Transmission to humans occurs through ingesting contaminated water or food. The major reservoir for cholera was long assumed to be humans themselves, but considerable evidence exists that aquatic environments can serve as reservoirs of the bacteria.

Vibrio cholerae is a Gram-negative bacterium that produces cholera toxin, an enterotoxin, whose action on the mucosal epithelium lining of the small intestine is responsible for the characteristic massive diarrhoea of the disease. In its most severe forms, cholera is one of the most rapidly fatal illnesses known, and a healthy person may become hypotensive within an hour of the onset of symptoms; infected patients may die within three hours if treatment is not provided. In a common scenario, the disease progresses from the first liquid stool to shock in 4 to 12 hours, with death following in 18 hours to several days without oral rehydration therapy.

Contents 1 Symptoms 2 Treatment 3 Epidemiology 3.1 Prevention 3.2 Susceptibility 3.3 Transmission 3.4 Biochemistry of the V. cholerae bacterium 4 See also 5 Original source

[edit] Symptoms

The diarrhea associated with cholera is acute and so severe that, unless oral rehydration therapy is started promptly, the diarrhea may within hours result in severe dehydration (a medical emergency), or even death.

Author Susan Sontag wrote that cholera was more feared than some other deadly diseases because it dehumanized the victim. Diarrhea and dehydration were so severe the victim could literally shrink into a wizened caricature of his or her former self before death.

Other symptoms include rapid dehydration, rapid pulse, dry skin, tiredness, abdominal cramps, nausea, and vomiting.

Traditionally, Cholera was widespread throughout third world countries, however more recently outbreaks have occurred in more rural parts of England and the United States' mid-west region.

[edit] Treatment

Water and electrolyte replacement are essential treatments for cholera, as dehydration and electrolyte depletion occur rapidly. Prompt use of oral rehydration therapy is highly effective, safe, uncomplicated, and inexpensive.

The use of intravenous rehydration may be absolutely necessary in severe cases, under some conditions.

In addition, tetracycline is typically used as the primary antibiotic, although some strains of V. cholerae exist that have shown resistance. Other antibiotics that have been proven effective against V. cholerae include cotrimoxazole, erythromycin, doxycycline, chloramphenicol, and furazolidone. Fluoroquinolones such as norfloxacin also may be used, but resistance has been reported. Recently Hemendra Yadav reported his findings at A.I.I.M.S., New Delhi that Ampicillin resistance has again decreased in V.cholerae strains of Delhi.

Rapid diagnostic assay methods are available for the identification of multidrug resistant V. cholerae. New generation antimicrobials have been discovered which are effective against V. cholerae in in vitro studies.

[edit] Epidemiology

[edit] Prevention

Although cholera can be life-threatening, prevention of the disease is straightforward if proper sanitation practices are followed. In the first world, due to advanced water treatment and sanitation systems, cholera is no longer a major health threat. The last major outbreak of cholera in the United States occurred in 1911. Travelers should be aware of how the disease is transmitted and what can be done to prevent it. Good sanitation practices, if instituted in time, are usually sufficient to stop an epidemic. There are several points along the transmission path at which the spread may be halted:

• Sterilization: Proper disposal and treatment of the germ infected fecal waste (and all clothing and bedding that come in contact with it) produced by cholera victims is of primary importance. All materials (such as clothing and bedding) that come in contact with cholera patients should be sterilized in hot water using chlorine bleach if possible. Hands that touch cholera patients or their clothing and bedding should be thoroughly cleaned and sterilized.
• Sewage: Treatment of general sewage before it enters the waterways or underground water supplies prevents undiagnosed patients from spreading the disease.
• Sources: Warnings about cholera contamination posted around contaminated water sources with directions on how to decontaminate the water.
• Water purification: All water used for drinking, washing, or cooking should be sterilized by boiling or chlorination in any area where cholera may be present. Boiling, filtering, and chlorination of water kill the bacteria produced by cholera patients and prevent infections from spreading. Water filtration, chlorination, and boiling are by far the most effective means of halting transmission. Cloth filters, though very basic, have significantly reduced the occurrence of cholera when used in poor villages in Bangladesh that rely on untreated surface water. Public health education and appropriate sanitation practices can help prevent transmission.

A vaccine is available in some countries (not the U.S.), but this prophylactic is not currently recommended for routine use by the CDC. The newer vaccine (brand name: Dukoral), an orally administered inactivated whole cell vaccine, appears to provide somewhat better immunity and have fewer adverse effects than the previously available vaccine.

[edit] Susceptibility

Recent epidemiologic research suggests that an individual's susceptibility to cholera (and other diarrhoeal infections) is affected by their blood type: Those with type O blood are the most susceptible, while those with type AB are the most resistant. Between these two extremes are the A and B blood types, with type A being more resistant than type B.

About one million V. cholerae bacteria must typically be ingested to cause cholera in normally healthy adults, although increased susceptibility may be observed in those with a weakened immune system, individuals with decreased gastric acidity (as from the use of antacids), or those who are malnourished.

It has also been hypothesized that the cystic fibrosis genetic mutation has been maintained in humans due to a selective advantage: heterozygous carriers of the mutation (who are thus not affected by cystic fibrosis) are more resistant to V. cholerae infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the gastrointestinal epithelium, thus reducing the effects of an infection.

[edit] Transmission

Persons infected with cholera have massive diarrhoea. This highly-liquid diarrhoea is loaded with bacteria that can spread to infect water used by other people. Cholera is transmitted from person to person through ingestion of water contaminated with the cholera bacterium, usually from feces or other effluent. The source of the contamination is typically other cholera patients when their untreated diarrhoea discharge is allowed to get into waterways or into groundwater or drinking water supply. Any infected water and any foods washed in the water, as well as shellfish living in the affected waterway, can cause an infection. Cholera is rarely spread directly from person to person. V. cholerae harbors naturally in the plankton of fresh, brackish, and salt water, attached primarily to copepods in the zooplankton. Both toxic and non-toxic strains exist. Non-toxic strains can acquire toxicity through a lysogenic bacteriophage. Coastal cholera outbreaks typically follow zooplankton blooms, thus making cholera a zoonotic disease.

[edit] Biochemistry of the V. cholerae bacterium

Most of the V. cholerae bacteria in the contaminated water that a host drinks do not survive the very acidic conditions of the human stomach. The few bacteria that do survive conserve their energy and stored nutrients during the passage through the stomach by shutting down much protein production. When the surviving bacteria exit the stomach and reach the small intestine, they need to propel themselves through the thick mucus that lines the small intestine to get to the intestinal wall where they can thrive. V. cholerae bacteria start up production of the hollow cylindrical protein flagellin to make flagella, the curly whip-like tails that they rotate to propel themselves through the mucous that lines the small intestine.

Once the cholera bacteria reach the intestinal wall, they do not need the flagella propellers to move themselves any longer. The bacteria stop producing the protein flagellin, thus again conserving energy and nutrients by changing the mix of proteins that 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 diarrhoea. 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.

Microbiologists have studied the genetic mechanisms by which the V. cholerae bacteria turn off the production of some proteins and turn on the production of other proteins as they respond to the series of chemical environments they encounter, passing through the stomach, through the mucous layer of the small intestine, and on to the intestinal wall. Of particular interest have been the genetic mechanisms by which cholera bacteria turn on the protein production of the toxins that interact with host cell mechanisms to pump chloride ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The chloride and sodium ions create a salt water environment in the small intestines which through osmosis can pull up to six liters of water per day through the intestinal cells creating the massive amounts of diarrhoea.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 diarrhoea.

By inserting separately, successive sections of V. cholerae DNA into the DNA of other bacteria such as E. coli that would not naturally produce the protein toxins, researchers have investigated the mechanisms by which V. cholerae responds to the changing chemical environments of the stomach, mucous layers, and intestinal wall. Researchers have discovered that there is a complex cascade of regulatory proteins that control expression of V. cholerae virulence determinants. In responding to the chemical environment at the intestinal wall, the V. cholerae bacteria produce the TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of virulence genes that produce the toxins that cause diarrhoea in the infected person and that permit the bacteria to colonize the intestine. Current research aims at discovering "the signal that makes the cholera bacteria stop swimming and start to colonize (that is, adhere to the cells of) the small intestine."

[edit] See also

• Bacterial diseases in India
• Anthrax
• Bacterial meningitis
• Diphtheria
• Leprosy
• Plague
• Rickettsial diseases
• Tuberculosis
• Yaws

[edit] Original source

This article was originally posted in Wikipedia.