Department of Infection Diseases
The Third Affiliated Hospital,
Sun Yat-sen University
Lai Jing
DEFINITION


Cholera was defined as Class A communicable diseases in the Law of the people’s
Republic of China for Prevention and
Control of Communicable Disease.
It’s also one of the quarantinable diseases as
stipulated by the International Health
Regulation (IHRs) .
DEFINITION



Cholera is an acute infection of intestinal
tract caused by Vibrio cholerae.
Clinical characteristics: a sudden onset of
severe watery diarrhea and vomiting, which
lead to dehydration even hypovolemic.
Appropriate fluid replacement is the key of
treatment and greatly reduces mortality.
ETIOLOGY Vibrio cholerae
Bacillus: curved, facultative anaerobic, gramnegative
motility with a single polar flagellum
the erratic movement
ETIOLOGY


Culture
 sensitive to low PH
 tolerant in alkaline condition
 alkaline peptone water : incubated in
stool sample or rectal swab
greater
sensitivity
Antigenic type
 flagellar H antigen
 somatic O antigen
ETIOLOGY

Classification
 V.
cholerae
V. cholerae O1*
non-O1 V. cholerae
(* agglutination in antisera the O1 group antigen)
 V.
cholerae O1
 O139
biotype classic
biotype EL Tor
strain: agglutinate in O group 139
specific antiserum
ETIOLOGY
 Serogroup


O1 and O139 strain cause
epidemic
Virulence: Cholera toxin (CT )
Resistance
sensitive to
 dryness
 heat
 sunlight
 common disinfectants
 acid, especially gastric acid
ETIOLOGY

When conditions in the environment such as
temperature, salinity and availability of
nutrients are suitable, V. cholerae can
survive for years in a free-living cycle
without the intervention of humans.
EPIDEMIOLOGY

A disease of antiquity
 the ancestral home of classic biotype : the
Ganges Delta of India
 subsequently spread to the world
 seven global pandemics: from 19th
century to date
 the biotype classic : the initial six
pandemics
EPIDEMIOLOGY
 biotype
EL Tor : recognized first at the
EL Tor quarantine station in the Persian
Gulf in 1911
 biotype EL Tor : 7th pandemic which
began in 1961
 V.cholerae O139: first designated in India
in late 1992
The distribution of cholera in the world
EPIDEMIOLOGY


Sources of infection
 patients
 subclinical patients? carriers?
Routes of transmission
large numbers of vibrios sources from the
voluminous liquid stools
 contaminated food
EPIDEMIOLOGY
 Contaminated
water (river, seawater, wells,
etc)
 flies: as media (contact
person to person)
the water-borne route
EPIDEMIOLOGY

Susceptibility of individuals
 generally susceptible
 more sensitive:
 individuals with low gastric production
 persons of blood group O
 children under 5 years
EPIDEMIOLOGY
 non-sustain
immunity from illness
 naturally acquired immunity :
V. cholerae O1 does not have cross-protect
against the O139 strain.
EPIDEMIOLOGY


Seasonality
 summer
 autumn
Endemic
 along the coast or the rivers
 regions lacking of safe water supplies

Cholera cases occured.

River overflowed the
villages and houses.

Drinking water was
contaminated.
peddlers
Most of cholera cases had
relation with contaminated food.
The nearest epidemic happened in HaiNan
providence in China.
Cholera in Zimbabwe

A new large cholera outbreaks have
happened in Zimbabwe since August 2008.

Cholera victims lie in a hospital ward in
Zimbabwe.


until the end of January 2009
 exceed 58, 000 cases: reported
 over 3, 000 people: died
The number of cholera deaths continues to
increase each day.

Cholera is closely linked to
 inadequate environmental management.
 lacking of sanitary water
 people drink contaminated water.

Recent interruptions to the water supplies,
together with overcrowding
PATHOGENESIS


Whether the disease develops or not
depends on:
the host’s non-specific immunity (gastric
acidity )
the amount of the bacteria ingested
Ingestion of V. cholerae
Resistant to gastric acid
Colonize small intestine
Illness occurs when viable organisms
reach the duodenum and jejunum.
PATHOGENESIS

Active motile vibros penetrate mucous
layers and attach to the brush border of the
intestinal epithelium where they secrete
cholera toxin (CT ).
Cholera toxin binds to intestinal cells
Chloride channels activated
Chloride ion-driven secretion, malabsorption of
sodium ion and water
Release large quantities of electrolytes &
bicarbonates
Fluid hypersecretion
Diarrhea
Dehydration
PATHOGENESIS

“Watery stool”:
 non-fecal
 enriched in water, potassium and
bicarbonate
 no plasma protein or formed elements of
the blood
 no cellular damage or inflammation
PATHOLOGY


The most prominent pathological findings:
dehydration in heart, liver, skin, etc
mild pathological changes in small intestine
CINICAL MANIFESTATIONS



Incubation: several hours ~ 7 days.
Clinical course of typical cases: three stages
 Stage of diarrhea and vomiting
 Stage of dehydration
 Stage of reaction and convalescence
All signs and symptoms drive from the fluid
losses.
CINICAL MANIFESTATIONS

Stage of diarrhea and vomiting
 sudden onset with severe diarrhea and
vomiting, several times to more than 10
times per day.
CINICAL MANIFESTATIONS
 Fluid
loss may be extreme, exceeding 1
liter per hour.
 rice-water stools: yellowish and watery or
clear with flecks of mucus
 no abdominal pain or tenesmus
 no fever in general
CINICAL MANIFESTATIONS

Stage of dehydration
 acidosis (loss of sodium bicarbonate )
 muscle cramps
 circulatory failure and renal failure
( hypovolumia )
 dehydration:
thirst
hoarse voice; exteme
depletion-sunken eyes
scaphoid abdomen
poor skin turgor
loss of skin elasticity
Table 1 Clinical findings according to degree of
dehydration
Finding
Mild
Dehydration
Moderate
Dehydration
Severe
Dehydration
Loss of fluid*
<5%
5%~10%
>10%
Mentation
Alert
Restless
Drowsy or comatose
Radial pulse rate
Normal
Rapid
Very rapid
Stystolic blood
pressure
Skin elasticity
Normal
Low
Very low
Retracts
rapidly
Normal
Retracts
slowly
Sunken
Retracts very slowly
Normal
Scant
oliguria
Eyes
Urine
prouduction
Very sunken
CINICAL MANIFESTATIONS

Stage of reaction and convalescence:
 recover from the disease if dehydration
corrected promptly.
 pyretic reaction
CINICAL MANIFESTATIONS
In rare instances cholera sicca shock and
death occur before diarrhea appears.
COMPLICATIONS

Acute renal failure

Acute pulmonary edema
DIAGNOSIS


Tentative diagnosis: clinical manifestations
and epidemiologic data
 Patient develops or dies from severe
watery diarrhea and dehydration in an
area where cholera is not endemic.
 Patient develops acute watery diarrhea in
an area where there is an epidemic or
cholera is endemic.
Definitive diagnosis: the isolation of the
V.cholerae from stool, vomit or rectal swab
DIFFERENTIAL
DIAGNOSIS


Bacterial food poisonings
Gastroenteritis
 enterotoxigenic E. coli
 enteropathogenic E. coli
 shigellosis
LABORATORY FINDINGS

Stool examinations
stool routine test: mucus and WBC
 dark-field microscopic examination:
darting motility of vibrios in fresh wet
preparations

LABORATORY FINDINGS
 stool
hanging drop examinations and
motility inhibition test:
The bacteria can be discerned by
immobilization with its serotype
antiserum.
 culture：alkaline peptone water or
thiosulfate-citrate-bile salt-sucrose (TCBS)
agar
Opaque flat yellow colonies form on TCBS
agar in 18 hours at 37℃.
LABORATORY FINDINGS


Blood examinations
 increased RBC, hemoglobin and WBC
 normal or decreased serum sodium,
serum potassium, increased BUN
 decreased CO2CP
Urine test: RBC, WBC, albumin, casts.
LABORATORY FINDINGS


Specific antibody in immobilization test :
epidemiological studies
Several other methods:
 latex agglutination
 enzyme immunoassay
 polymerase chain reaction (PCR)
TREATMENT

Isolation:
 6 days after the symptoms disappear
 before 3 negative stools cultures taken
once every other day
TREATMENT

Fluid replacement

The goal: restore the fluid losses
 start
as soon as diarrhea begins
 two phases: rehydration phase
maintenance phase
 two routes: intravenous fluids, oral fluids
TREATMENT
 Intravenous
fluids
 severe or moderate cases
or in shock
 the main principles: early, rapid and
enough
infuse of salt solution according to the
reaction to the treatment
 correct of the metabolic acidosis
 give potassium if patients without oliguria

Table 2 The volume of intravenous fluids in
first 24 hours
Volume of
infusion
Mild
Moderate
Severe
Dehydration Dehydration Dehydration
adult（ml） 3000～4000 4000～8000 8000～12000
child
120～150
（ml/kg）
salt solution 60～80
（ml/kg）
150～200
200～250
80～100
100～120
(5: 4: 1 solution: NaCl 5g, NaHCO3 4g, KCl 1g and
50% GS 20 ml in per liter of water. )
TREATMENT

Oral fluids
 mild cases
 severe cases in
which the patient’s condition has
improved after giving intravenous fluids
TREATMENT
 Oral
rehydration solution (ORS):
 NaCl 3.5, NaHCO3 2.5, KCl 1.5 and
GS 20 in grams per liter of water per
liter water
 The volume in the initial 6 hours: adult
750ml/h; child 15~20ml/kg
 The total volume is decided as the
degree of dehydration and ongoing
fluid loss.
TREATMENT

Antibiotics:
 reduce
the duration of diarrhea
 decrease excretion of the V. cholerae
 norfloxacin, doxycycline, berberine or
SMZ-TMP

Treatment of complications
 acute
renal failure
 acute pulmonary edema
PREVENTION

Control of sources of infection
 The diarrhea clinic need be established.
 Case must be reported to CDC within 6
hours in towns or within 12 hours in
villages.
 all patients: strictly isolated in wards
PROGNOSIS



Without treatment, mortality approaches 60
per cent of those affected.
Management
The clinical type
PROGNOSIS

The mortality is always in greater among
 the aged and young children
 the intemperate and those poorly
nourished
 treatment is not vigorous in the early
stage of the disease
PREVENTION
 close

contacts
 medical
surveillance for 5
days
 take SMZ-TMP
or norfloxacin for
2 days
all carriers
 detection and
treatment
PREVENTION

Interruption of the routes of transmission
 correct the water supply and sewage
system as a matter of urgency
PREVENTION
 provision
of facilities for sanitary
disposal of human waste
 education on good personal hygiene
 a wide variety of disinfectants are
effective: bleaching power, soap
 adhering to proper food safety
practices
PREVENTION

Increase the immunity of individuals
 Vaccination: different vaccine strains

Once an outbreak has started, WHO does not
recommend oral cholera vaccine or parenteral
cholera vaccine.
 The
vaccine’s limited efficacy is at least
partially due to its failure to induce a local
immune response at the intestinal mucosal
surface.