CHOLERA

MEDICAL STUDENT MI LECTURE

BY
N.A. DANKIRI ( FMCP)
 OUTLINE
• INTRODUCTION
• MICROBIOLOGY
• PATHOPHYSIOLOGY
• RISK FACTORS
• CLINICAL PRESENTATION
• DIAGNOSIS
• TREATMENT
 INTRODUCTION
• An acute diarrheal illness caused by infection of the
intestine by bacteria Vibrio cholerae.
• Cholera is an acute diarrheal disease that can, in a matter of
hours, result in profound, rapidly progressive dehydration
and death.
• Endemic in many countries in Africa and Asia.
• World wide estimates from the WHO 2020
-1.3 to 4.0 million new cases of cholera each year
-21,000 to 143,000 deaths each year
• Infects both male and females equally
• More severe in children and the elderly
 Microbiology

• All Vibrio species are highly motile, facultatively anaerobic,

curved gram-negative rods with one or more flagella.
• More than 200 serotypes have been identified based on the O
antigen.
• Only O1 and O139 are responsible for epidemic cholera in
humans.
• O1 is divided into two biotypes, classical and El Tor, on number
biochemical characteristics and susceptibility to specific phages.
• Both biotypes are further divided into Inaba, Ogawa, and
Hikojima based on subspecificity of the O1 antigen
• Inaba (antigen A and C), Ogawa (antigen A and
B) and Hikojima(antigen A, B and C)
• Classic biotype -causes equal number of
symptomatic vs asymptomatic
• El Tor biotype -causes more asymptomatic
infection
 Pathogenesis/pathophysiology
• The natural habitat of V. cholerae is coastal salt water and brackish estuaries, where
the organism lives in close relation to plankton.
• Pathogenic only to humans
• Humans and water are the only known reservoirs
• Mode of transmission
• -contaminated water
• -contaminated food
• -direct contact ???
• Infectious dose varies with the vehicle
• -103to 109when water is the vehicle
• -102to 104 when food is the vehicle
• The organism does not invade the intestinal wall or reach the blood stream
• While the infectious dose is relatively high, it is markedly reduced in hypochlorhydric
persons, in those using antacids, and when gastric acidity is buffered by a meal.
• MECHANISM; Cholera is a toxin-mediated disease.
• The watery diarrhea characteristic of cholera is due
to the action of cholera toxin, a potent protein
enterotoxin elaborated by the organism in the small
intestine.
• The toxin-coregulated pilus (TCP), so named
because its synthesis is regulated in parallel with
that of cholera toxin, is essential for V. cholerae to
survive and multiply in (colonize) the small intestine
• Once established in the human small bowel, the organism
produces cholera toxin, which consists of a monomeric enzymatic
moiety (the A subunit) and a pentameric binding moiety (the B
subunit).
• The B subunit binds to GM1 ganglioside, a glycolipid on the
surface of epithelial cells that serves as the toxin receptor and
makes possible the delivery of the A subunit to its cytosolic target.
• The activated A subunit (A1) irreversibly transfers ADP-ribose and
binds it to G protein of adennylate cyclase.
• These results in upregulates the activity of adenylate cyclase; the
result is the intracellular accumulation of high levels of cyclic AMP.
• In intestinal epithelial cells, cyclic AMP inhibits the absorptive
sodium transport system in villus cells and activates the
secretory chloride transport system in crypt cells, and these
events lead to the accumulation of sodium chloride in the
intestinal lumen.
• Since water moves passively to maintain osmolality, isotonic
fluid accumulates in the lumen. When the volume of that fluid
exceeds the capacity of the rest of the gut to resorb it, watery
diarrhea results.
• Unless the wasted fluid and electrolytes are adequately
replaced, shock (due to profound dehydration) and acidosis
(due to loss of bicarbonate) follow.
• The stool osmolar gap is < 50mosm/kg.
 Risk factors
• Environmental factors
• -certain human habits favoring water and soil pollution
• -low standard of personnel hygiene
• -lack of education and poor quality of life
• -climatic change
• Host factors

• -Raw or undercooked food i.e shellfish

• -Blood group O patients
• -Decreased gastric acidity
• 1) Use of antiacids
• 2) Histamine receptor blockers
• 3) Gastrectomy
• 4) Chronic gastritis induced by helicobacter pylori
 Clinical findings

• Incubation period: 1 to 2 days on average

• Diarrhea ; painless watery diarrhea that may quickly
become voluminous .Bile and faecal matter can be seen in
the early phase of infection
• The diarrhea has fishy odor in the beginning, but became
less smelly & like “rice water” in few hours
• Fever is usually absent.
• Muscle cramps due to electrolyte disturbances are common
• Vomiting
• Dehydration, shock & death if untreated
• Signs and symptoms of dehydration
• -dry mucous membranes
• -decreased skin turgor
• -sunken eyes
• -dry axilla, no tears
• Hypotension
• Clinical symptoms parallel volume contraction:
• At losses of <5% of body weight (mild); thirst
develops.
• At 5-10% (moderate); postural hypotension,
weakness, tachycardia and decrease skin turgor.
• At losses of 10% (severe); oliguria, weak or
absent pulses, sunken eyes (and, in infants,
sunken fontanelles), wrinkled (“washerwoman”)
skin, somnolence, and coma are characteristic.
Rice water
• Cholera gravis-severe cholera;
• Very watery “rice water stool”
• Up to 6liters of stool per hour in adult-rapid
dehydration and shock
• Rapidly lose more than 10%of body weight
• Death within 12hours or less
• Cholera sicca
• Rare atypical presentation that causes ileus
with fluid swelling in the intestines without
diarrhea
• Increased fatality, with death resulting from
toxemia before the onset of diarrhea
 Complications

• Acute kidney injury

• Electrolyte depletion
• Hypoglycemia mostly in children
• Seizures
• Mental alteration
• Pneumonia secondary to aspiration ( if
convulse or unconscious)
 Diagnosis

• Diagnosis can be Clinical

• -Cholera should be considered in all cases with
severe watery diarrhea and vomiting
-Travelling to affected areas or eating raw
shellfish
• Organism can be seen in stool by direct
microscopy after gram stain & dark field exam
is used to demonstrates motility.
• Cholera can be cultured on special alkaline
media like triple sugar agar or thiosulphate-
citrate-bile salt-sucrose (TCBS) agar plate.
• Other investigations;
• Electrolyte ( low biocarbonate) and elevated
urea
• Full blood count ( mild neutrophilic
leucocytosis)
 Treatment
• Rehydration
• Antibiotics
• Feeding
 Treatment-Rehydration
• Rehydration phase:
• -restore normal hydration status
• -should take not more than 4hours
• -ringers lactate preferred over normal saline rate of 50-
100mls/kg/hr.

• Maintenance phase:
• -Maintain normal hydration status by replacing ongoing
losses
• -Oral route is preferred, the use of ORS at a rate of 500-
1000ml/hr
 Treatment-Antibiotics
• Antibiotic treatment: Advantages;
• -prompt eradication of the vibrio
• -diminished the duration of the diarrhea
• -decreased fluid loss
• Antibiotics should be administered to moderate and severe cases
• Recommended antibiotic
• -Ciprofloxacin 1g as a single dose
• -Tetracycline 500mg qid for 3days
• -Doxycycline 300mg single dose
• -Co-trimoxazole 1tab bd for 3 days
• -Azithromycin 1g as a single dose
• -Furazolidone
• Zinc therapy
• -zinc inhibits cAMP induced, chlorine
dependent fluid secretion
• -zinc inhibits basolateral K+ channel
• -boost the immune system
 Differential diagnosis
• Rota virus gastroenteritis
• Enterotoxigenic E. coli
• Bacterial food poisoning
• Shigella
• Campylobacter
• Salmonella
 Prevention
• Safe water supply
• Proper management of excreta
• Surveillance
• Vaccination
 Vaccination
• Dukoral
• -oral inactivated whole cell of 4 strains plus recombinant B subunit
• -2 doses needed
• -not licenced for children < 2years
• Sanchol
• -bivalent cholera vaccine
• -booster dose recommended after 2 years
• Vaxchora
• -indicated for active immunization against V. cholerae sero group
01
• -approved for adult 18-64years of age
 Chemoprophylaxis
• Advised only for close household contacts or a
closed community in which cholera has
occurred
• Tetracycline is the drug of choice
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