CHOLERA (VIBRIO CHOLERA)

Introduction

Cholera, sometimes known as Asiatic cholera or epidemic cholera, is an infectious gastroenteritis caused by the bacterium Vibrio cholerae.[1][2]

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.[1]

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.[1]

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.[

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.[5]

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.

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.[6] Fluoroquinolones such as norfloxacin also may be used, but resistance has been reported.[7]

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.[8] New generation antimicrobials have been discovered which are effective against V. cholerae in in vitro studies.

Holding or transport media

Venkataraman-ramakrishnan (VR) medium: This medium has 20g Sea Salt Powder and 5g Peptone dissolved in 1L of distilled water.

Cary-Blair medium: This the most widely-used carrying media. This is a buffered solution of sodium chloride, sodium thioglycollate, disodium phosphate and calcium chloride at pH 8.4.

Autoclaved sea water

Enrichment media

Alkaline peptone water at pH 8.6 Monsur's taurocholate tellurite peptone

water at pH 9.2

Vaccine for cholera

A recently developed oral vaccine for cholera is licensed and available in other countries (Dukoral from SBL Vaccines).

The vaccine appears to provide somewhat better immunity and have fewer adverse effects than the previously available vaccine.

However, CDC does not recommend cholera vaccines for most travelers, nor is the vaccine available in the United States . Further information about Dukoral can be obtained from the manufacturers:

Dukoral ® SBL Vaccin AB, SE-105 21 Stockholm, Swedentelephone +46-8-7351000,e-mail: info@sblvaccines.sewebsite: www.sblvaccines.se

Pathogenesis and Epidemiology of cholera

Virulence factor Colonization of the small Intestinal Mucosa Cholera toxin Other toxin produced by V. cholerae Virulence gene Cassette: ctx, ace and zot Transcriptional Regulation of Virulence

Genes toxR, ToxS, ToxT System

Plating media

Alkaline bile salt agar (BSA): The colonies are very similar to those on nutrient agar.

Monsur's gelatin Tauro cholate trypticase tellurite agar (GTTA) medium: Cholera vibrios produce small translucent colonies with a greyish black centre.

TCBS medium: This the mostly widely used medium. This medium contains thiosulphate, citrate, bile salts and sucrose. Cholera vibrios produce flat 2-3 mm in diameter, yellow nucleated colonies.

Direct microscopy of stool is not recommended as it is unreliable. Microscopy is preferred only after enrichment, as this process reveals the characteristic motility of Vibrios and its inhibition by appropriate antiserum. Diagnosis can be confirmed as well as serotyping done by agglutination with specific sera.

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

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