Cholera is a bacterial disease caused by Vibrio cholerae that causes severe watery diarrhea and dehydration. It occurs in outbreaks related to contaminated water supplies in areas with poor sanitation. Clinical presentation includes sudden onset of painless, copious watery diarrhea and vomiting leading to severe dehydration and death if untreated. Diagnosis is confirmed by identifying the bacteria in a stool sample. Treatment focuses on oral rehydration and intravenous fluids to replace fluid and electrolyte losses. Antibiotics are given to shorten the duration of illness and reduce spread.
2. Definition
Cholera is a bacterial disease that affects
the intestinal tract.
It is caused by Vibrio cholerae.
.While cholera is a rare disease in US and
Europe, those who may be at risk include
people traveling to foreign countries where
outbreaks are occurring.
3. Epidemics
Epidemics occur after war, or natural
disasters when water and food supplies
become contaminated with V cholera due
poor sanitation.
In the United States and Europe, because of
sanitation systems, cholera is not a major
threat.
In developing countries outbreaks of cholera
continue every year.
4. Cholera, 2009
In 2009, the number of cases of cholera reported
to WHO increased by 16% when compared with
2008.
A total more then 200 000 cases, including 5000
deaths, were reported from 45 countries; the
case-fatality rate (CFR) was 2.24% .
Global trends during the past 20 years have
shifted from a high incidence in the Americas
during the early 1990s to a high incidence in
Africa, with few cases reported from Asia
5. History
. Records from Hippocrates (460-
377 BC) and Galen (129-216 AD)
The seventh pandemic of cholera,
caused by V cholerae O1, biotype El
Tor, began in 1961 and continues
today. Reports also document
endemics caused by biotype O139.
6. History and epidemyology
Robert Koch discovered V cholerae in 1883
during an outbreak in Egypt.
The organism is, gram-negative aerobic bacillus
whose size varies from 1-3 μm (micrometres)
Its antigenic structure consists of a flagellar H
antigen and a somatic O antigen.
The differentiation of the latter allows for
separation into pathogenic and nonpathogenic
strains.
V cholerae O1 and V cholerae O139 are
associated with epidemic cholera
7. Biotypes and serotypes
V cholerae O1 is classified into 2 major biotypes:
Classic 01 and El Tor. Currently, El Tor is the
predominant cholera pathogen.
Organisms in both biotypes are subdivided into
serotypes according to the structure of the O
antigen, as follows:
Serotype Inaba - O antigens A and C
Serotype Ogawa - O antigens A and B
Serotype Hikojima - O antigens A, B, and C
8. Pathophysiology
The infectious dose of bacteria required to cause
clinical disease varies by the mode of administration
. If ingested with water, the infectious dose is 103 -
106 organisms.
When ingested with food, fewer organisms (102 -104
organisms) are required to produce disease.
The use of antacids, H receptor blockers, and proton
pump inhibitors increases the risk of cholera
infection as a result of reduced gastric acidity.
The same applies to patients with chronic
gastritissecondary to Helicobacter pylori infection or
those who have undergone a gastrectomy.
9. Pathophisiology and
manifestations 1
Cholera is a toxin-mediated disease.
The clinical features and epidemiologic
manifestations of disease caused by
cholera O139 are indistinguishable
from those caused by O1
10. Cholera toxin (CTX) is
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.
Pathophysiology 2
11. Pathophysiology 3
Because the organism is not acid-
resistant, it depends on its large
inoculum size to bypass gastric acidity.
motility, chemotaxis, and elaboration of
hemagglutinin/protease to invade the
mucous layer of the small intestine.
12. Pathophysiology 4
V cholerae O1 and V cholerae O139 cause
clinical disease by producing an enterotoxin
that promotes the secretion of fluid and
electrolytes into the lumen of the small
intestine.
The enterotoxin is a protein molecule
composed of 5 B subunits and 2 A subunits.
The B subunits are responsible for binding
to a ganglioside ( GM1) receptor located on
the surface of the intestinal mucosa cells
13. Diarrhea mechanism
The activation of the A1 subunit by adenylate
cyclase is responsible for the increasing in
cyclic adenosine monophosphate (cAMP).
cAMP blocks the absorption of sodium and
chloride by the microvilli and promotes the
secretion of chloride and water by the crypt
cells.
The result is watery diarrhea with electrolyte
concentrations isotonic to those of plasma.
14. NOTE!
The enterotoxin acts locally and
does not invade the intestinal wall.
As a result, few neutrophils are
found in the stool.
15. Age
In nonendemic 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.
16. Mortality/Morbidity
If untreated, the disease rapidly results
in dehydration and can result in death
in more than 50% of infected
individuals.
The mortality rate is increased in
pregnant women and children.
17. Clinical presentation
Incubation period 24- to 48-hour
Onset - sudden of painless watery diarrhea
that may quickly become severe and
profuse.
The patient may experience accompanying
abdominal cramps.
The stool may contain fecal material early in
the course of clinical illness.Then The
diarrhea becames more watery like "rice
water" with fishy odor
Fever is typically absent
In patients with severe disease, the stool
volume can exceed 250 mL/kg in the first 24
hours.
19. Сlinical presentation
V cholerae does not elicit an inflammatory
response, and cholera stool contains few
leukocytes and no erythrocytes.
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.
20. V cholerae course
However, often V cholerae infections may
be asymptomatic, mild or moderate
diarrhea and may not be clinically
distinguished from other causes of
gastroenteritis.
An estimated 5% of infected patients will
develop cholera gravis, ie, severe watery
diarrhea, vomiting, and dehydration
21. Vomiting
Vomiting, although a prominent
manifestation, may not always be present.
It occurs early in the course of the disease
.
22. Dehydration
Dehydration can be developed rapidly,
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.
27. Categories of Dehydration
Dehydration has been classified into
the following 3 categories : severe,
some (previously termed moderate in
the WHO criteria for the classification
of dehydration), and none (previously
termed mild by the WHO).
28. Physical
Clinical signs of cholera parallel the level
of amount of fluid loss
The amount of fluid loss and the corresponding
clinical signs of cholera are as follows:
l. 3-5% loss of normal body weight - Excessive thirst
ll. 5-8% loss of normal body weight - Postural
hypotension, tachycardia, weakness, fatigue, and
dry mucous membranes or dry mouth
lll.> 10% loss of normal body weight - Oliguria;
sunken eyes; sunken fontanelles in infants; weak,
thready pulse; wrinkled "washerwoman" skin;
somnolence; and coma
29. Condition Eyes Tears
Mouth
and
Tongue
Thirst
Skin
Pinch
Decision
Well, alert Normal Present Moist Drinks
normally,
not
thirsty
Goes
back
quickly
Patient has no signs of
dehydration.
*Restless,
irritable
Sunken Absent Dry *Thirsty,
drinks
eagerly
*Goes
back
slowly
If the patient has 2 or
more signs, including at least 1 *
sign, some dehydration is
present.
*Lethargic or
unconscious,
Very
sunken
and dry
Absent Very dry Thirst
may be
missing
*Goes
back
very
slowly
If the patient has 2 or more signs,
including at least 1 * sign, severe
dehydration is present.
Assessment of the Patient With Diarrhea for Dehydration
30. Children
Children with some (moderate) dehydration
have lost approximately 7-10% of body water
(approximately 5% of body weight).
Children have decreased skin turgor, as
manifested by prolonged skin response to a skin
pinch test (the most reliable sign of isotonic
dehydration), and a normal pulse.
Children without clinically significant dehydration
(<5% loss of body weight) may have increased
thirst without other signs of dehydration.
31. Children-differences from adult
Children with severe cholera may present with signs
that are rarely seen in adults.
A child with cholera is usually very somnolent, and
coma is not uncommon.
Pediatric patients may have convulsions due ,in
part, to hypoglycemia because of diminished food
intake during the acute illness, exhaustion of
glycogen stores.
Acidosis in cholera is a result of bicarbonate loss in
stool and accumulation of lactate and inadequate
Respiratory compensation
Another significant difference from the adult
presentation is that children are often febrile.
32. Hypokalemia
Results from potassium loss in the stool,.
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 can also produce hypocalcemia by
decreasing the proportion of serum calcium that
is ionized.
33. Chvostek and Trousseau signs
The Chvostek sign (also
Weiss sign) is one of the
signs of tetany seen in
hypocalcemia.
It refers to an abnormal
reaction to the stimulation of
the facial nerve.
When the facial nerve is
tapped at the angle of the jaw
(i.e. masseter muscle), the
facial muscles on the same
side of the face will contract
momentarily due
hyperexcitability of nerves.
34. Trousseau signs
Tonic spasm of
muscles after the
hand jamming
neurovascular
forearm or shoulder
35. Other
:
O(l) blood group: The role played by O blood group
is less certain. The cause is unknown, but incidence
of infection appears to be twice as high in this
population.
Second infections complications rarely occur or are
mild.
Asymptomatic carriers: This may have a role in
transfer of disease in areas where the disease is not
endemic.
Although carriage usually is short-lived, a few
individuals may excrete the organisms for a
prolonged period.
37. Laboratory Studies
Diagnosis may be confirmed via
identification of V cholerae in the stool.
The organism may be detected directly
with dark-field microscopy examination of
fresh stool; chaotic motility is observed.
The serotype may be determined by
immobilization with Inaba-specific or
Ogawa-specific antiserum.
38. Laboratory isolation
Laboratory isolation
requires a selective
medium. V cholerae
grows as a flat, yellow
colony on thiosulfate-
citrate-bile salts-
sucrose agar or
taurocholate-tellurite-
gelatin agar.
More recently,
polymerase chain reaction
(PCR) has been used with
a high degree of sensitivity
and specificity
39. Hematological tests
.
Hematocrit, are elevated in
dehydrated patients because of
resulting hemoconcentration.
When patients are first observed,
they generally have a leucocytosis
without a left shift.
40. Serum electrolytes
Serum sodium is usually 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.
Bicarbonate concentration usually is less than 15
mmol/L in severely dehydrated patients and often is
nondetectable.
41. Renal profile
1.BUN and serum creatinine levels are elevated,
reflecting the decrease in glomerular filtration.
The extent of their elevation is dependent on the
degree and duration of dehydration.
2.Other biochemical tests
Blood glucose measurement and blood gases
and bicarbonate concentration are important
parameters to monitor and treatment as
required.
42. Medical Care instructions
The WHO's guidelines for the
management of cholera are the most
practical, easily understood, and applied in
clinical practice.
These guidelines can be used for the
treatment of any patient with diarrhea and
dehydration.
Diagnosis of cholera is not mandatory
before therapy.
43. Steps in the treatment of a patient with
suspected cholera
Step 1: Assess for dehydration. Assess the
degree of dehydration and categorize it into
severe dehydration, some dehydration, or no
signs of dehydration.
Step 2: Rehydrate the patient and monitor
frequently. Then reassess hydration status.
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.
44. Goal of the rehydration
The goal of the rehydration phase is to
restore normal hydration status, which
should take no more than 4 hours.
Set the rate of infusion in severely
dehydrated patients at 50-100 mL/kg/h.
Lactated Ringer solution is preferred over
isotonic sodium chloride solution because
saline does not correct metabolic acidosis
46. Severe dehydration
Administration intravenous (IV) fluid immediately to
replace fluid deficit with 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 .
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.
47. Rehydration regime
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
48. Monitoring
Reassess the patient after 3 hours (infants
after 6 h). If signs of severe dehydration
(rare) still exist, repeat the IV therapy
already given.
If signs of some dehydration are present,
continue oral rehydration
If no signs of dehydration exist, maintain
hydration by replacing ongoing fluid losses
49. Maintenance phase
The objective of the
maintenance phase is to
maintain normal
hydration status by
replacing ongoing
losses.
The oral route is
preferred, and the use of
oral rehydration solution
(ORS) at a rate of 500-
1000 mL/h is
recommended.
50. Some dehydration
Administer ORS solution according to the amount recommended in Table 3.
Table 3. Approximate Amount of ORS Solution to Administer in the First 4 Hours
]
Age* <4
mo
4-11
mo
12-
23
mo
2-4 y 5-14
y
³ 15 y
Weight <5
kg
5-
7.9
kg
8-
10.9
kg
11-
15.9
kg
16-
29.9
kg
³ 30
kg
ORS
solution in
mL
200-
400
400-
600
600-
800
800-
1200
1200-
2200
2200-
4000
•Use the patient's age only when weight is unknown.
51. Patients who are first observed with no signs of dehydration
can be treated at home.
No signs of dehydration
Age Amount of Solution After Each Loose Stool
<24 mo 50-100 mL
2-9 y 100-200 mL
>10 years As much as is wanted
52. Note!
Most patients absorb enough ORS
solution to achieve rehydration, even when
they are vomiting. Vomiting usually
subsides within 2-3 hours, as rehydration
is achieved.
. Regular urinary output (ie, every 3-4 h) is
a good sign that enough fluid is being
given
53. Cholera cots
In areas where cholera is endemic,
cholera-cots have been used to assess
the volume of ongoing stool losses.
A cholera cot is a cot covered by a plastic
sheet with a hole in the center to allow to
collect the stool in a calibrated bucket.
54. Diet
Resume feeding with a normal diet when
vomiting has stopped.
Continue breastfeeding infants and young
children.
Malnutrition after infection is not a major
problem, as observed after infection with
Shigella species or rotavirus diarrhea.
55. Medication
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.
56. The mane rules
If the patient is severely dehydrated and older
than 2 years, administer an antibiotic.
Initiate the antibiotic after the patient has been
rehydrated (usually in 4-6 h) and vomiting has
stopped.
No advantage exists to using parenteral
antibiotics, which are expensive.
No other drugs should be used in the treatment
of cholera
57. Antibiotic Single
Dose (PO)
Multiple Dose (PO)
Doxycycli
ne†
7 mg/kg;
not to
exceed
300
mg/dose‡
2 mg/kg bid on day 1; then 2 mg/kg qd on
days 2 and 3; not to exceed 100 mg/dose
Tetracycli
ne†
25 mg/kg;
not to
exceed 1
g/dose‡
40 mg/kg/d divided qid for 3 d; not to exceed 2
g/d
Furazolido
ne
7 mg/kg;
not to
exceed
300
mg/dose
5 mg/kg/d divided qid for 3 d; not to exceed
400 mg/d
58. Trimethoprim
and
sulfamethoxaz
ole
Not
evaluated
<2 months: Contraindicated
>2 months: 5-10 mg/kg/d (based on trimethoprim
component) divided bid for 3 d; not to exceed 320 mg/d
trimethoprim and 1.6 g/d of sulfamethoxazole
Ciprofloxacin§ 30 mg/kg;
not to
exceed 1
g/dose‡
30 mg/kg/d divided q12h for 3 d; not to exceed 2 g/d
Ampicillin Not
evaluated
50 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Erythromycin Not
evaluated
40 mg/kg/d erythromycin base divided tid for 3 d; not to
exceed 1 g/d
59. Complications of therapy and
prognosis
Overhydration with parenteral fluid therapy
presents with the earliest sign of puffiness of
eyelids. If not recognized at this stage, it may
lead to pulmonary edema
Prognosis
Before the development of effective regimens for
replacing fluids and electrolyte losses, the
mortality rate in severe disease was more than
50%.
Mortality rates are lowest where intravenous
therapy is available.
60. Prevention
Early identification and case management
Rapid identification of cases in children and adults
and prompt treatment will limit further spread of the
disease.
Surveillance systems
Surveillance systems can provide an early alert to
outbreaks, which should lead to a coordinated
response and efforts.
Multisectoral approach .
A multisectoral and coordinated approach is
paramount to efficiently control a cholera outbreak.
Key sectors to be involved are health, water and
sanitation, fishery and agriculture, and education.
61. Prevention
Personal hygiene, food preparation, and health
education
Vaccines
Parenteral vaccines have been discontinued
because of their poor efficacy.
WHO has identified 3 oral vaccines, which are
available in some countries but are used mainly by
travelers.
Efforts are underway to identify further use of these
vaccines in endemic and epidemic situations