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By:- Dinesh Gajera

 History  Symptoms
 What is cholera?  Diagnosis
 How does a person get  Colonization of the
cholera? Small Intestine
 Cholera Toxin  Treatment
 Mechanism of action of cholera  Prevention
enterotoxin  Vaccine
 Susceptibility  Research
 Transmission

 Cholera was originally endemic to the Indian

subcontinent, with the Ganges River likely serving as a
contamination reservoir.

 It spread by trade routes (land and sea) to Russia, then

to Western Europe, and from Europe to North America.

 It is now no longer considered an issue in Europe and

North America, due to filtering and chlorination of the
water supply.

 In January 1991, epidemic cholera appeared in South

America and quickly spread to several countries.

 A few cases have occurred in the United States

among persons who traveled to South America or ate
contaminated food brought back by travelers.
What is cholera?

 Cholera is an acute, diarrhea illness caused by infection of the

intestine with the bacterium Vibrio cholerae.

 The infection is often mild or without symptoms, but

sometimes it can be severe. Approximately one in 20 infected
persons has severe disease characterized by profuse watery
diarrhea, vomiting, and leg cramps.

 In these persons, rapid loss of body fluids leads to

dehydration and shock. Without treatment, death can occur
within hours.
How does a person get cholera?
 A person may get cholera by drinking water or eating food
contaminated with the cholera bacterium.

 In an epidemic, the source of the contamination is usually the

feces of an infected person.

 The disease can spread rapidly in areas with inadequate

treatment of sewage and drinking water.
 The cholera bacterium may also live in the environment
in brackish rivers and coastal waters.

 Shellfish eaten raw have been a source of cholera, and

a few persons in the United States have contracted
cholera after eating raw or undercooked shellfish from
the Gulf of Mexico.
Cholera Toxin

 Cholera toxin activates the adenylate cyclase enzyme in

cells of the intestinal mucosa leading to increased levels of
intracellular cAMP, and the secretion of H20, Na+, K+, Cl-, and
HCO3- into the lumen of the small intestine.
 The effect is dependent on a specific receptor,
monosialosyl ganglioside (GM1 ganglioside) present on the
surface of intestinal mucosal cells.
 The bacterium produces an invasin, neuraminidase, during
the colonization stage which has the interesting property of
degrading gangliosides to the monosialosyl form, which is
the specific receptor for the toxin.

 The toxin has been characterized and contains 5 binding (B)

subunits of 11,500 daltons, an active (A1) subunit of 23,500
daltons, and a bridging piece (A2) of 5,500 daltons that links
A1 to the 5B subunits.

 Once it has entered the cell, the A1 subunit enzymatically

transfers ADP ribose from NAD to a protein (called Gs or Ns),
that regulates the adenylate cyclase system which is located
on the inside of the plasma membrane of mammalian cells.
Mechanism of action of cholera
 Cholera toxin approaches target cell surface.

 B subunits bind to oligosaccharide of GM1 ganglioside.

Conformational alteration of holotoxin occurs, allowing the
presentation of the A subunit to cell surface.

 The A subunit enters the cell.

 The disulfide bond of the A subunit is reduced by intracellular

glutathione, freeing A1 and A2.
 NAD is hydrolyzed by A1,
yielding ADP-ribose and

 One of the G proteins of

adenylate cyclase is ADP-
ribosylated, inhibiting the
action of GTPase and locking
adenylate cyclase in the "on"

 Recent epidemiologic research suggests that a person's

susceptibility to cholera (and other diarrheas) is affected by
their blood type.

 Those with type O blood are the most susceptible. Those

with type AB are the most resistant, virtually immune.

 Between these two extremes are the A and B blood types,

with type A being more resistant than type B.

 V. cholerae occurs naturally in the plankton of fresh,

brackish, and salt water, attached primarily to copepods in
the zooplankton.

 Coastal cholera outbreaks typically follow zooplankton

blooms. This makes cholera a zoonosis. Cholera is then
transmitted through ingestion of feces contaminated with
the bacterium.

 The contamination usually occurs when untreated sewage

is released into waterways or into groundwater, affecting
the water supply, any foods washed in the water, and
shellfish living in the affected waterway — it is rarely spread
directly from person to person.

 Symptoms include those of general GI tract upset, including

profuse diarrhoea.

 Symptoms are caused by the enterotoxins that V. cholerae

produces. The main enterotoxin, known as cholera toxin,
interacts with G proteins and cyclic AMP in the intestinal
lining to open ion channels.

 As ions flow into the intestinal lumen , water follows through

due to osmosis.

 Your doctor will examine you and ask you about your

 He or she will also ask you a number of questions such as

which countries or regions you have recently visited
(including any stopovers).

 Your doctor may ask you for a stool sample. The sample will
be sent to a laboratory for examination to find out if you are
infected with cholera bacterium.5
Colonization of the Small

 There are several characteristics of pathogenic V. cholerae that are

important determinants of the colonization process.

 These include adhesins, neuraminidase, motility, chemotaxis and

toxin production. If the bacteria are able to survive the gastric secretions
and low pH of the stomach, they are well adapted to survival in the small

 V. cholerae is resistant to bile salts and can penetrate the mucus layer
of the small intestine, possibly aided by secretion of neuraminidase and
proteases (mucinases).
 They withstand propulsive gut motility by their own swimming ability and
chemotaxis directed against the gut mucosa.

 Treatment typically consists of aggressive rehydration and

replacement of electrolytes , since the death rate is generally
high due to the serious dehydration caused by the illness.

 Tetracycline antibiotics may have a role in reducing the

duration and severity of cholera, although drug-resistance is
occurring and their effects on overall mortality is questioned
18Other antibiotics that have been used include ciprofloxacin
and azithromycin.
 Nurses encouraging this patient to drink an Oral
Rehydration Solution to improve dehydration he acquired
from cholera.

 Although cholera can be life-threatening, it is easily

prevented. In the United States and Western Europe,
because of advanced water and sanitation systems, cholera is
not a major threat.

 The last major outbreak of cholera in the United States was in


 However, everyone, especially travellers, should be aware of

how the disease is transmitted and what can be done to
prevent it.

 Simple sanitation is usually sufficient to stop an epidemic. There are

several points along the transmission path at which the spread may
be halted.

 Sickbed: Proper disposal and treatment of waste produced by

cholera victims.
 Sewage: Treatment of general sewage before it enters the
 Sources: Warnings about cholera contamination posted around
contaminated water sources.
 Sterilization: Boiling, filtering, and chlorination of water before use.

 Researchers have tested a potential vaccine against cholera

and found it to be safe and effective in a study population.
 The potential vaccine, called Peru-15, is being developed for
use by persons who live outside regions affected by cholera,
including travelers and military personnel.

 The safety test was the first step in evaluating Peru-15 as a

potential vaccine, which then could also be used in areas
where cholera is endemic, according to the researchers.

 The oral vaccine was created from a strain of the bacterium

Vibrio cholerae isolated in Peru in 1991 (the O1 El Tor Inaba

 The researchers deleted a core group of genes that encode

virulence factors and cholera toxins.

 This made Peru-15 less virulent and safe for testing in


 Cholera has been a laboratory for the study of evolution of


 Prior to partition, both regions had Cholera pathogens with

similar characteristics. After 1947, India made more progress
on public health than Bangladesh.

 As a consequence, the strains of the pathogen which

succeeded in India had a greater incentive in the longevity of
the host, and are less virulent than the strains prevailing in
Bangladesh, which uninhibitedly draw upon resources of the
host thus rapidly killing him.