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Cholera
By:- Dinesh Gajera
M.sc(microbiology)
Sem-3
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CONTENTS
History
What is cholera?
How does a person get
cholera?
Cholera Toxin
Mechanism of action of cholera
enterotoxin
Susceptibility
Transmission
Symptoms
Diagnosis
Colonization of theSmall Intestine
Treatment
Prevention
Vaccine Research
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History
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 andNorth America, due to filtering and chlorination of the
water supply.
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Cont..
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.
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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, butsometimes 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.
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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 thefeces of an infected person.
The disease can spread rapidly in areas with inadequate
treatment of sewage and drinking water.
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Cont..
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.
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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.
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Cont..
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 locatedon the inside of the plasma membrane of mammalian cells.
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Mechanism of action of cholera
enterotoxin
Cholera toxin approaches target cell surface.
B subunits bind to oligosaccharide of GM1 ganglioside.
Conformational alteration of holotoxin occurs, allowing thepresentation 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.
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Cont..
NAD is hydrolyzed by A1,yielding ADP-ribose andnicotinamide.
One of the G proteins ofadenylate cyclase is ADP-ribosylated, inhibiting theaction of GTPase and locking
adenylate cyclase in the "on"mode.
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Susceptibility
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.
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Transmission
V. cholerae occurs naturally in the plankton of fresh,
brackish, and salt water, attached primarily to copepods inthe zooplankton.
Coastal cholera outbreaks typically follow zooplanktonblooms. This makes cholera a zoonosis. Cholera is thentransmitted through ingestion of feces contaminated withthe bacterium.
The contamination usually occurs when untreated sewageis released into waterways or into groundwater, affectingthe water supply, any foods washed in the water, andshellfish living in the affected waterway it is rarely spread
directly from person to person.
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Symptoms
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.
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Diagnosis
Your doctor will examine you and ask you about your
symptoms.
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
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Colonization of the Small
Intestine
There are several characteristics of pathogenic V. cholerae that are
important determinants of the colonization process.
These include adhesins, neuraminidase, motility, chemotaxis andtoxin 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
intestine.
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.
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Treatment
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 ciprofloxacinand azithromycin.
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Prevention
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
1911.
However, everyone, especially travellers, should be aware of
how the disease is transmitted and what can be done to
prevent it.
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Cont..
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
waterways. Sources: Warnings about cholera contamination posted around
contaminated water sources.
Sterilization: Boiling, filtering, and chlorination of water before use.
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vaccine
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 foruse 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 apotential vaccine, which then could also be used in areas
where cholera is endemic, according to the researchers.
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Cont..
The oral vaccine was created from a strain of the bacterium
Vibrio cholerae isolated in Peru in 1991 (the O1 El Tor Inaba
strain).
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
people.
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Research
Cholera has been a laboratory for the study of evolution ofvirulence.
Prior to partition, both regions had Cholera pathogens withsimilar characteristics. After 1947, India made more progresson public health than Bangladesh.
As a consequence, the strains of the pathogen whichsucceeded in India had a greater incentive in the longevity ofthe host, and are less virulent than the strains prevailing inBangladesh, which uninhibitedly draw upon resources of thehost thus rapidly killing him.
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Reference
www.google.com
www.wikipedia.com
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