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Cholera
1. Cholera
Cholera is a disease of the intestines, caused by the bacterium Vibrio
cholerae, which is passed via the fecal-oral route Signs and symptoms of
cholera typically show up 2-3 days after infection, but they can occur
within hours of exposure, or in as much as five days In its severe form,
the disease causes profuse watery diarrhea, vomiting, and leg cramps
The rapid onset of dehydration can cause shock and death within hours .
Vibrio cholerae is a Gram-negative, comma-shaped bacterium. The
bacterium's natural habitat is brackish or saltwater. Some strains of V.
cholerae cause the disease cholera. V. cholerae is a facultative
anaerobe[1] and has a flagellum at one cell pole as well as pili. V.
cholerae can undergo respiratory and fermentative metabolism. When
ingested, V. cholerae can cause diarrhea and vomiting in a host within
several hours to 2-3 days of ingestion.
Characteristics
V. cholerae is Gram-negative and comma-shaped. Initial isolates are
slightly curved, whereas they can appear as straight rods upon laboratory
culturing. The bacterium has a flagellum at one cell pole as well as pili.
V. cholerae is a facultative anaerobe, and can undergo respiratory and
fermentative metabolism.
2. Pathogenesis
V. cholerae pathogenicity genes code for proteins directly or indirectly
involved in the virulence of the bacteria. During infection, V. cholerae
secretes cholera toxin, a protein that causes profuse, watery diarrhea
(known as "rice-water stool"). Colonization of the small intestine also
requires the toxin coregulated pilus (TCP), a thin, flexible, filamentous
appendage on the surface of bacterial cells. V. cholerae can cause
syndromes ranging from asymptomatic to cholera gravis. In endemic
areas, 75% of cases are asymptomatic, 20% are mild to moderate, and 2-
5% are severe forms such as cholera gravis. Symptoms include abrupt
onset of watery diarrhea (a grey and cloudy liquid), occasional vomiting,
and abdominal cramps. Dehydration ensues, with symptoms and signs
such as thirst, dry mucous membranes, decreased skin turgor, sunken
eyes, hypotension, weak or absent radial pulse, tachycardia, tachypnea,
hoarse voice, oliguria, cramps, renal failure, seizures, somnolence,
coma, and death. Death due to dehydration can occur in a few hours to
days in untreated children. The disease is also particularly dangerous for
pregnant women and their fetuses during late pregnancy, as it may cause
premature labor and fetal death. In cases of cholera gravis involving
severe dehydration, up to 60% of patients can die; however, less than
1% of cases treated with rehydration therapy are fatal. The disease
typically lasts 4–6 days. Worldwide, diarrhoeal disease, caused by
cholera and many other pathogens, is the second-leading cause of death
3. for children under the age of 5 and at least 120,000 deaths are estimated
to be caused by cholera each year. In 2002, the WHO deemed that the
case fatality ratio for cholera was about 3.95%.
The Actions of Cholera Toxin
When cholera toxin is released from the bacteria in the infected
intestine, it binds to the intestinal cells known as enterocytes (epithelial
cell in above diagram) through the interaction of the pentameric B
subunit of the toxin with the GM1 ganglioside receptor on the intestinal
cell, triggering endocytosis of the toxin. Next, the A/B cholera toxin
must undergo cleavage of the A1 domain from the A2 domain in order
for A1 to become an active enzyme. Once inside the enterocyte, the
enzymatic A1 fragment of the toxin A subunit enters the cytosol, where
it activates the G protein Gsa through an ADP-ribosylation reaction that
acts to lock the G protein in its GTP-bound form, thereby continually
stimulating adenylate cyclase to produce cAMP. The high cAMP levels
activate the cystic fibrosis transmembrane conductance regulator
(CFTR), causing a dramatic efflux of ions and water from infected
enterocytes, leading to watery diarrhoea.
One area of anti-diarrhoea treatment lies in the stimulation of
enkephalins, which regulate intestinal secretion by acting directly on
enterocytes. Enkephalins bind to the opioid receptors on enterocytes,
which act through G proteins to inhibit the stimulation of cAMP
4. synthesis induced by cholera toxin, thereby directly controlling ion
transport.
Treatment & Prevention
Cholera offers a number of points of intervention for its prevention:
Identify infectives (stool samples or rectal swabs)
Properly dispose of fecal matter
Ensure potable water supplies for drinking, bathing, cooking, cleaning,
and brushing of teeth
Avoid eating foods that may be contaminated (undercooked meat and
seafood; unpeeled fruits)
5. Get vaccinated
Treatment involves one or both of:
Fluid replacement (Oral Rehydration Therapy; IV fluids in severe or
advanced cases)
Antibiotic therapy
6. Get vaccinated
Treatment involves one or both of:
Fluid replacement (Oral Rehydration Therapy; IV fluids in severe or
advanced cases)
Antibiotic therapy