CHOLERA

Dinesh k lamsal :MD

 Introduction

Cholera is an infection of the small intestine

caused by the bacterium Vibrio cholerae.
It causes a large amount of watery
diarrhea
Background:
*The appellation for cholera probably
derives from the Greek word for the gutter
of a roof, comparing the deluge of water
following a rainstorm to that of the anus
of an infected person.

* Cholera is an ancient disease caused by

Vibrio cholerae O1 or, more recently, by V
cholerae O139.
Contd…

* The hallmark for the disease is profuse

secretory diarrhea.
*Cholera can be spread as an endemic,
epidemic, or pandemic disease.
*Despite all the major advances in research,
the condition still remains a challenge to
the modern medical world.
Causes, incidence, risk factors
• Caused by The gram –ve enteroccocibacilus
,vibrio cholera
• The toxin released by the bacteria causes
increased secretion of water and chloride ions in
the intestine, which can produce massive
diarrhea.
• Death can result from the severe dehydration
brought on by the diarrhea.

• Cholera occurs in epidemics when conditions of

poor sanitation, crowding, war, and famine are
present.

next….
Contd…
• Endemic areas include India ,Nepal,( Asia),
Africa, the Mediterranean, and more recently,
South and Central America, and Mexico.

• A type of vibrio bacteria also has been

associated with shellfish, especially raw oysters.

Risk factors :
• include residence or travel in endemic areas and
exposure to contaminated or untreated drinking
water.
Epidemiology
Internationally:
• Periodic global or pandemic spread of
cholera from its endemic reservoir in the
Indian subcontinent was recognized as
characteristic of cholera as early as 1831.
• In 1990, fewer than 30,000 cases were
reported to the WHO. Reported cases
increased more than 10-fold with the
beginning of the Latin American epidemic in
1991.
Next….
Contd…..
• In 1994, the number of cases (384,403) and
countries (94) reporting cholera was the largest
ever registered at the WHO.
• Even Europe experienced a 30-fold increase in
cholera from 1993-1994.
• In 1998, another surge in the number of cases
occurred, with the number almost doubling that
reported in 1997.
• In 2004, a total of 56 countries officially
reported cholera activity to WHO.
• Africa and Asia continue to report the highest
number of cases
Mortality/Morbidity:
• In 1950, during the sixth pandemic, case fatality
rates were very high, and as many as 50-70% of
patients died.

• With the replacement of classic cholera with El

Tor, a less virulent strain, case fatality rates
reduced dramatically during the 1960s

• Fatality rates have declined further because of

better treatment and, in particular, increasingly
available oral rehydration therapy, which was
introduced during the early 1970s but became
widely available in many parts of the world in
the 1980s.
Next…..
Contd…..
• For most patients, treatment with oral
rehydration is sufficient; however, when safe
water or oral rehydration salts are not available,
case fatality rates can be very high.

• A case fatality rate of 25-50% was estimated

among untreated patients in refugee camps.
Where good treatment is readily accessible, the
case fatality rate is less than 1%.

next….
Contd……

• In Africa, a marked decline in case fatality rates

has occurred since 1970;

• however, Africa continues to have the highest

reported case fatality rates (approximately 5% in
1998 and 4% in 1999) compared to the rest of
the world.

• Average case fatality rates for Europe and the

Americas continue to however around 1%.
Contd…..
Age:
In non-endemic areas, incidence of infection is
similar in all age groups, although adults are less
likely to become asymptomatic than children.

• The exception is breastfed children, who are

protected against severe disease because of less
exposure and because of the antibodies to
cholera they obtain in breast milk.
 Pathophysiology:
• Cholera vibrios multiply in the small bowel.->
• Adhere to the mucosal surface & secrets
exotoxin (enterotoxin) ->
• Stimulates cAMP (adenyl cyclase-adenosine
monophosphate) pathway of the mucosa .->
• Resulting outpouring of small bowel fluid &
toxin too.->
• Alter gut motility & makes sever dehydration
,dyselectromia
• Leading to acidosis ,hypoglycemia ,renal failure
too.-
 Contd….

The species V cholerae has been classified according to

the carbohydrate determinants of its somatic O
antigens.

Approximately 140 serotypes have been defined

these are classified as those agglutinate in antisera to

the O1 group antigen (V cholerae O1)

next….
Contd…..
• those that do not agglutinate in antisera to the
O1 group antigen (non-O1 V cholerae).

V cholerae O1 was the cause of most pandemics

until a new strain.

V cholerae O139 (non-O1 type), was recognized

as a cause of epidemic in southern India and
parts of Bangladesh in 1992.
Contd…..1
Cholera toxin (CTX) is a potent protein
enterotoxin elaborated by the organism in
the small intestine.>>
To reach the small intestine, however, the
organism has to negotiate the normal
defense mechanisms of the GI tract.>>
next….
Contd….
Because the organism is not acid-resistant,
it depends on its large inoculum size to
bypass gastric acidity.>>

Using its own properties, such as motility,

chemotaxis, and elaboration of
hemagglutinin/protease, the organism
transcends the mucous layer of the small
intestine.>>
Contd….2
Hemagglutinin/protease is both an
agglutinin and a zinc-dependent protease,
which cleaves the mucin and fibronectin
as well as a subunit of CTX.>>
Hemagglutinin/protease also may serve to
facilitate the spread and excretion of
vibrios within the intestine in stools by
detaching them from the intestinal
walls.>>
next….
Contd..
*the vibrios adhere to the intestinal wall
mediated by toxin-coregulated pilus
(TCP).>>
The synchronous working of TCP, CTX, and
a few other virulence factors all are
regulated by toxR gene product, which is
designated as the "master switch.“>>
Contd….3
Once established, the organisms produce CTX that
consists of subunits A and B.>>
The B subunit is the binding subunit, and the A
subunit is the enzymatic subunit.>>
These 2 working in harmony, transfer adenosine
diphosphate (ADP) and activate it to cyclic
adenosine monophosphate (cAMP).>>
which inhibits the absorptive sodium transport and
activates the excretory chloride transport in the
intestinal crypt cells, eventually leading to an
accumulation of sodium chloride in the intestinal
lumen.>>

next….
Contd……4
• The high osmolality in the intestinal lumen
is balanced by water secretion that
eventually overwhelms the lumen
absorptive capacity and leads to
diarrhea.>>
• Unless the wasted fluid and electrolytes
are replaced adequately, shock (caused by
profound dehydration) and acidosis
(caused by loss of bicarbonate) follow.>>
Contd…..
• The O139 Bengal strain of V cholerae has
a very similar pathogenic mechanism
except that it produces a novel O139
lipopolysaccharide (LPS) and an
immunologically related O-antigen
capsule.>>
• These 2 features enhance its virulence
and increase its resistance to human
serum in vitro and occasional development
of O139 bacteremia.
Clinical presentation

Symptoms & signs :

• Sudden onset of watery diarrhea, up
to 1 liter (quart) per hour
– Diarrhea has a "rice water" appearance --
the stool looks like water with flecks of
rice in it
– Diarrhea has a "fishy" odor
Contd….
• Dehydration can occur rapidly
– Rapid pulse (heart rate)
– Dry skin
– Dry mucous membranes or dry mouth
– Excessive thirst
– Glassy eyes or sunken eyes
– Lack of tears
– Lethargy
– Unusual sleepiness or tiredness
– Low urine output
– Sunken "soft spots" (fontanelles) in infants
• Abdominal cramps
• Nausea
• Vomiting

Note: Symptoms can vary from mild to severe.

 Clinical phases:
Evacuation phase –
abrupt onset of painless profuse ,watery
diarrhea associated with vomiting, rice watery
Stool (mucus flecks)

Collapse phase –
shock, dehydration ,reduced urine out- put,
pt’s apathetic ,muscles cramps, renal-failure
child –convulsion ,hypoglycemia
Recovery phase –coming to normal,
History:
Diarrhea
– Profuse watery diarrhea is a hallmark of cholera.

– Cholera should be suspected when a patient older than 5 years

develops severe dehydration from acute, severe, watery diarrhea
(usually without vomiting)

– or in any patient older than 2 years who has acute watery diarrhea in
an area where an outbreak of cholera has occurred.

– Stool volume during cholera is more than that of any other infectious
diarrhea. Patients with severe disease may have a stool volume of more
than 250 mL/kg body weight in a 24-hour period.

– The stool may contain fecal material early in the course of clinical
illness.

next…..
Contd…..
– The characteristic cholera stool is an opaque
white liquid that is not malodorous and often
is described as having a rice water
appearance (ie, in color and consistency, it
resembles water that has been used to wash
or cook rice).
– V cholerae does not elicit an inflammatory
response, and cholera stool contains few
leukocytes and no erythrocytes.
Next….
Contd….
– Because of the large volume of diarrhea,
patients with cholera have frequent and often
uncontrolled bowel movements.
– Patients experience abdominal cramps,
probably caused by distention of loops of
small bowel as a result of the large volume of
intestinal secretions.
Vomiting
– Vomiting is a prominent manifestation of
illness.
– It occurs early in the course of the disease
when the vomiting is caused by decreased
gastric and intestinal motility
– If untreated, the diarrhea and vomiting lead
to isotonic dehydration and, in patients with
severe disease, vascular collapse, shock, and
death.

Next…
Contd……
– Dehydration can develop with remarkable
rapidity, within hours after the onset of
symptoms.
– This contrasts with disease produced by
infection from any other enteropathogen.
– Because the dehydration is isotonic, water
loss is proportional between 3 body
compartments, intracellular, intravascular, and
interstitial.
 Physical signs: dehydration
• Assessment of the Patient With Diarrhea for Dehydration

• Condition: -------- Well, alert > Restless, irritable >Lethargic

or unconscious, floppy
• Eyes: -------- Normal > Sunken > Very sunken and dry
• Tears: --------- Present > absent > absent
• Mouth and Tongue coated :--- moist > dry > very dry
• Skin Pinch:----- Goes back quickly > Goes back slowly >
Goes back very slowly

Next…
Contd….
Decision:------
* Patient has no signs of dehydration.
* If the patient has 2 signs, including at
least 1major sign, some dehydration
* If the patient has more than 2 signs,
including at least 2 major sign, severe
dehydration.
Contd…1

– In adults and children older than 5 years, other signs for

severe dehydration include absent radial pulse and low
blood pressure.

– The skin pinch may be less useful in patients with

marasmus (severe wasting), kwashiorkor (severe
malnutrition with edema), or obesity.

– Tears are relevant signs only for infants and young

children.

next….
Contd….
1.severe dehydration :
– have a characteristic clinical appearance that
is attributable to the loss of approximately
15% of total body water (approximately 10%
of total body weight).
– Intracellular and intravascular dehydration is
manifested in decreases skin turgor, sunken
eyes, and wrinkled ("washer woman") hands.
Contd….2

– Decreased intravascular volume is manifested

by tachycardia, absent or barely palpable
peripheral pulses, and hypotension.

– Tachypnea and hypercapnia also are part of

the clinical picture and are attributable to the
metabolic acidosis that invariably is present in
patients with cholera who are dehydrated.

next…
Contd…..
2. some (moderate) dehydration:
– have lost approximately 7-10% of body water
(approximately 5% of body weight).
– In these patients, cardiac output and vascular
resistance are normal, and changes in interstitial and
intracellular volume are the primary manifestations of
illness.
– Children have decreased skin turgor, as manifested
by prolonged skin tenting in response to a skin pinch
(the most reliable sign of isotonic dehydration), and a
normal pulse.

3. without clinically significant dehydration :

(<5% loss of body weight) may have increased thirst
without other signs of dehydration.
 25……
Metabolic and systemic manifestations
– After dehydration, hypoglycemia is the most
common lethal complication of cholera in children.
– Hypoglycemia is a result of diminished food intake
during the acute illness, exhaustion of glycogen
stores, and defective gluconeogenesis secondary to
insufficient stores of gluconeogenic- substrates in
fat and muscle.

next……
Contd…

– Acidosis in cholera is a result of bicarbonate

loss in stools, accumulation of lactate because
of diminished perfusion of peripheral tissues,
and hyperphosphatemia.

– Acidemia occurs when respiratory

compensation is unable to sustain a normal
blood pH.
Contd….4
– Hypokalemia
results from potassium loss in the stool, with a
mean potassium concentration of
approximately 30 mmol/L.
– when first observed, despite severe total body
potassium depletion.
– Hypokalemia develops only after the acidosis
is corrected and intracellular hydrogen ion is
exchanged for extracellular potassium.
Next….
Contd……

– Hypokalemia is most severe in children with

preexisting malnutrition who have diminished
body stores of potassium and may be
manifested as paralytic ileus.

– Rehydration therapy with bicarbonate-

containing fluids also can produce
hypocalcemia by decreasing the proportion of
serum calcium that is ionized.
 Types of fluids :
Na+ C l- K+,Hco3 meq/l

N.Saline 150 150 ----,----- 300

(0.9%)
R/L 131 111 5 , 29 181

4%Dex./ 30 30 ---------- 60
(.18 %
NS)
0.45% NS 75 75 ----------- 150
 Investigation
Lab Studies:
microscopic examination:
Gram stain: Although observed as a gram-negative
organism, the characteristic motility of Vibrio
species cannot be identified on a Gram stain.
• Dark field organism :characteristic motility can be
examined :by adding Vibrio antisera
• Culture:
• Serotyping and biotyping
– Specific antisera can be used in immobilization tests.

next….
 Contd…1
• Hematological tests
– The major laboratory derangements in patients with cholera derive from
the alterations in intravascular volume and electrolyte concentrations.

– Hematocrit,
serum-specific gravity, and serum protein are elevated in dehydrated
patients because of resulting hemo-concentration.
– When patients are first observed, they generally have a leucocytosis
without a left shift.

next…..
Contd…2

• Serum electrolytes
– Serum sodium usually is 130-135 mmol/L, reflecting
the substantial loss of sodium in the stool that has
accompanied the water.
– Serum potassium usually is normal in the acute phase
of the illness, reflecting the exchange of intracellular
potassium for extracellular hydrogen ion in an effort
to correct the acidosis.(3-5.5 mmol/l)

– Bicarbonate concentration usually is less than 15

mmol/L in severely dehydrated patients and often is
nondetectable.
 Contd….3
Renal profile:
• Blood urea nitrogen and serum creatinine are
elevated, reflecting the decrease in glomerular
filtration.
• The extent of their elevation is dependent on the
degree and duration of dehydration.

Other biochemical tests:

Blood glucose measurement and blood gases and
bicarbonate concentration

• The management of any watery diarrhea is basically

replacing the lost fluid and electrolytes and providing
an antimicrobial .
 Treatment
• The objective of treatment is to replace fluid and electrolytes
lost through diarrhea.

• To start antibiotics therapy for control the toxins , produced by

bacteria

• Depending upon condition, fluids may administrate by mouth

or through a vein (intravenous).

• Tetracycline and other antibiotics may shorten the time of

illness.

next…..
Contd….
• Note: Tetracycline is usually not prescribed
for children

• The World Health Organization (WHO) has

developed an oral rehydration solution
that is cheaper and easier to use than the
typical intravenous fluid.
• This solution of sugar and electrolytes is
now being used internationally.
 Contd….1
Medical Care:

• The WHO's guidelines for the management of cholera are the most practical,
easily understood, and applied in clinical practice.

• Diagnosis of cholera is not mandatory before therapy.

• Steps in the treatment of a patient with suspected cholera

• Step 1:
– Assess for dehydration. As described earlier, Table can be used to assess the
degree of dehydration and categorize it into severe dehydration, some
dehydration, or no signs of dehydration

next…..
Contd…2
Step 2:
– Rehydrate the patient and monitor frequently. Then
reassess hydration status. The primary objectives of
the treatment of patients with cholera are to correct
dehydration, if present, and then maintain hydration.
Step 3:
– Maintain hydration. Replace ongoing fluid losses until
diarrhea stops.
Step 4:
– Administer an oral antibiotic to the patient with
severe dehydration.
Step 5:
– Feed the patient.
 Contd….2
Severe dehydration :

• Administer IV fluid immediately to replace fluid deficit.

• Use lactated Ringer solution or, if not available, isotonic
sodium chloride solution.
• Start IV fluid immediately. If the patient can drink, begin
giving oral rehydration salt (ORS) solution by mouth while
the drip is being set up.

For patients older than 1 year,

give 100 mL/kg IV in 3 hours—30 mL/kg as rapidly as
possible (within 30 min) then 70 mL/kg in the next 2 hours.
For patients younger than 1 year,
administer 100 mL/kg IV in 6 hours—30 mL/kg in the first
hour then 70 mL/kg in the next 5 hours.
 Contd…2a
Monitor the patient very frequently.
* After the initial 30 mL/kg have been
administered, the radial pulse should be strong
and blood pressure should be normal.
* If the pulse is not yet strong, continue to
give IV fluid rapidly.
* Administer ORS solution (about 5 mL/kg/h)
as soon as the patient can drink, in addition to
IV fluid.
* urine out put – should be pass urine by 0.5
–I ml/kg /hr
Contd…..
Reassess the patient
* after 3 hours (infants after 6 h), using Table

If signs of severe dehydration

(rare) still exist, repeat the IV therapy already given.

If signs of some dehydration

are present, continue fluid as indicated for some
dehydration.

If no signs of dehydration
exist, maintain hydration by replacing ongoing fluid
losses.
 Contd….3
Some dehydration :

Approximate Amount of ORS Solution to Administer in the First 4 Hours

Age1<4 mo Weight
<5 kg
in mL200-400

• 4-11 mo
5-7.9 kg
--400-600 ml

• 12-23 mo ,
8-10.9 kg -- 600-800 ml

next…..
Contd…..
• 2-4 y
11-15.9 kg- 800-1200 ml

• 5-14 y ,
16-29.9 kg
1200-2200 ml
•
³15 y
³30 kg
ORS solution 2200-4000
ml
No signs of dehydration :
Age
Amount of Solution
After Each Loose Stool
• <24 mo : 50-100 mL ,Enough for 500 mL/d
• 2-9 y :100-200 mL , Enough for 1000 mL/d
• >10 yrs : As much as is wanted . Enough for 200 mL/d

Maintenance of hydration :
Age
Amount of Solution
After Each Loose Stool
<24 mo : 100 mL
2-9 y : 200 mL
10 yrs : much as is wanted

next….
 Use of oral antibiotics
In patients with severe dehydration

• An effective antibiotic can reduce the volume of

diarrhea in patients with severe cholera and shorten
the period during which V cholerae O1 is excreted.

• In addition, it usually stops the diarrhea within 48

hours, thus shortening the period of hospitalization.

• If the patient is severely dehydrated and older than

2 years, administer an antibiotic.
next…….
Contd….
• Begin antibiotic therapy after the patient has been
rehydrated (usually in 4-6 h) and vomiting has stopped.
• No advantage exists to using injectable antibiotics, which
are expensive.
• No other drugs should be used in the treatment of
cholera.
• Correction of electrolytes : deficit
eg .Na-> (Normal require-deficit m mol /l X wt X 0.6)
• k -> normal- observed x wt. x 0.3
Name of antibiotics: cifro-floxacine , metronidazole
tetracycline ,doxycycline , cotrim, erythromycine.
 Prevention:
*cholera vaccination
*sanitation ,education,
*AB: tetracycline-3days
Complications
• Severe dehydration-disorriented
• Shock (hypo-volumic)
• dyselectromia
• dysarrythmia
• Death
prognosis

• Severe dehydration can cause death.

• Given adequate fluids, most people will
make a full recovery.

thank you