Cholera

Introduction
•Acute diarrhoeal disease
•Causative organism Vibrio cholerae Classical
El Tor
•Nowadays commonly due to El Tor biotype
•Majority of infections are mild or asymptomatic
•Case fatality as high as 30%-40% (unless rapid
replacement of fluid and electrolytes)
Typical cases:
• Onset of profuse, effortless, watery diarrhoea
followed by
• Rapid dehydration
• Muscular cramps
• Suppression of urine
Global Scenario
• In 2015 - 42 countries reported a total of
172,454 cases including 1304 deaths, resulting in
an overall case fatality ratio (CFR) of 0.8%.
• Afghanistan, the Democratic Republic of the
Congo (DRC), Haiti, Kenya, and the United
Republic of Tanzania accounted for 80% of all
cases.
• In 2014 - 190 549 cases

*Source: WER WHO 2016 and 2015

• In 2015 - 23 countries reported a total of
1304 cholera-related deaths; 937 deaths
occurred in Africa, 30 in Asia, and 337 in
the Americas.
• In 2015 a total of 80 cases of cholera was
reported by Nepal to WHO with 0 deaths
making it a case fatality rate of 0%.

*Source: WER WHO 2016 and 2015

Status in Nepal

*Source Annual Health Report 2072/73

Year No. of Cases No. of Deaths Case Fatality Rate
(CFR)
2015 80 0 0%

2014 933 2 0.21%

2012 34 0 0%

2011 12 0 0%
 Epidemiological features
•Both epidemic and endemic
•Epidemicity and endemicity depend on
1)Characteristics of agent
Ability to survive
Its virulence
Average no of organism required to cause
infection
2) Characteristics of the system
Number of susceptibles
Opportunities for transmission of infection
Epidemics

• Characteristically abrupt
• High potential to spread fast
• Self limiting in nature
• Reaches a peak and subsides as “force of infection” declines.
• Self limiting due to acquisition of temporary immunity and
due to occurrence of large number of sub clinical cases
Force of infection
• 2 components
1)Force of infection through water
2) Force of infection through contacts

• Elimination of contaminated water doesn’t immediately bring

outbreak to an end
• Rather a so called “Tail” of epidemics is produced. This is due
to continuation of transmission through contacts.
Endemics
• Doesn’t show stable endemicity like typhoid
• Shows seasonal fluctuation
• Seasonal variation differs between countries and even
regionsof same country.
• El Tor biotype has higher tendency to cause endemicity
– Causes higher infection to case ratio(i.e. inapparant infections and
mild cases)
 What is the fate of
vibrio cholerae in the
inter-epidemic
period???
• Three explanations:
(A) The existence of long term carriers
(B) The existence of diminished but continuous transmission
involving asymptomatic cases
(C) The persistence of the organism in free living form in the
environment
Epidemiological determinants
• Agent factors:
1.Agents
- Causative organism – Vibrio cholerae 0 group 1 or Vibrio
cholerae O1 and 0139.
- Also known as epidemic strains
- Vibrios that are biochemically similar to epidemic strains but
do not agglutinate in Vibrio cholerae 0 and 0139 antiserum
are referred as Non agglutinating (NAG) vibrios/ non cholera
vibrios/ non epidemic strains.
- Some NAG vibrios are pathogenic for humans (e.g. Vibrio
parahemolyticus) – have caused outbreaks of cholera like
diarrhoea
 Vibrio
cholerae 0
group 1

El tor Classical

Ogawa Inaba Hikojima

• Resistance :
- Killed within 30 minutes by heating at 56⁰C
- Within a few seconds by boiling
- Remain in ice for 4-6 weeks or longer
- Destroyed easily by cresol and bleaching powder
• Toxin production :
- Produces exotoxin (enterotoxin) in small intestine
- Diarrhoea through its effect on adenylate cyclase – cyclic
AMP system of mucosal cells.
• Reservoir of infection:
- Human are only known reservoir of cholera infection
- Cases range from unapparent infection to severe ones.
- About 75% people do not develop symptoms although
bacteria is present in faeces for 7-14 days.
- Among people who develop symptoms 20% develop acute
watery diarrhoea with severe dehydration.
- People with low immunity (malnourished and HIV) are at
greater risk if infected.
• Infective material: immediate sources are stools and
vomits of Case and carriers.
- In cases large numbers(i.e.107 -109 Vibrios /ml of
fluid)
- In carriers fewer numbers(i.e. 102-105 Vibrios
/gm of stool)
• Infective dose:
- Dose related
- infection when : number of vibrios ingested >
dose that is infective for the individual.
Host factors
• Age and sex : affects all age and both sex
• Gastric acidity: - Effective barrier
- Vibrio is destroyed in pH 5 or lower
- conditions reducing gastric acidity increase susceptibility
• Population mobility: Movement of population results in
increased risk of exposure to infection
• Economic status: incidence highest in lower economic group
• Immunity :
- infection followed by immunity to reinfection
- Specific IgA antibodies in lumen of intestine
- Duration and degree of immunity are not known
Environmental factors

• Transmission is readily possible in a community with

poor environmental sanitation
• Important factors are contaminated food and water
• Flies may carry V. cholerae but are not vectors of
proven importance
• Low standards of personal hygeine,lack of education
and poor quality of life.
Mode of transmission
Transmission occurs from man to man via
a) Faecally contaminated water
b) Contaminated food and drinks
c) Direct contact

Incubation period
From a few hours to 5 days, but commonly 1-2
days
 Carriers in cholera
• A cholera carrier is an apparently healthy
person who is excreting V. cholerae O1
(classical or El Tor) in stools.
• There are four types of cholera carriers:
a) Preclinical or Incubatory Carriers
b) Convalescent Carrier
c) Contact or Healthy Carrier
d) Chronic Carrier
Pathogenesis
• The cholera vibrio gets through the mucus which
overlies the intestinal epithelium. It secretes
mucinase which helps it move rapidly through the
mucus. Then it gets attached to the intestinal
epithelial cells with the help of adherence factors in
its surface.

• After this it produces enterotoxin which consists to

two parts the Light or L toxin and the Heavy or H
toxin. The L toxin combines with the gangliosides in
the epithelial cell membrane and this binds the
Vibrio to the cell membrane irreversibly
• The H toxin activates the Adenylyl Cyclase in the
intestinal epithelial cells. The activated Adenylyl
Cyclase causes a rise in 3,5-AMP also called as cAMP.
• This cAMP provides energy which drives the fluid and
electrolytes out of the cell to the intestinal lumen
• This fluid is isotonic and is secreted by all segments
of the small intestine. The increase in fluid is the
cause of diarrhoea.
• There is no evidence of V. cholera invading any tissue
nor the enterotoxin to cause any direct effect on any
organ other than the small intestine.
Clinical features:
A typical case of cholera shows 3 stages:

a) Stage of evacuation:
abrupt onset profuse painless watery diarrhoea
followed by vomiting. As many as 40 stools that
may have “rice water” appearance
b) Stage of collapse:
Occurs because of dehydration. The classical
signs are:
i) sunken eyes
ii) hollow cheeks
iii) scaphoid abdomen
iv) sub normal temperature
v) washerman’s hands and feet
vi) absent pulse
vii) unrecordable blood pressure
 viii) loss of skin elasticity
ix) shallow and quick respiration
x) decreased urine output that may
eventually cease
xi) restlessness, intense thirst and cramps

Death may occur at this stage due to dehydration and

acidosis
c) Stage of recovery:
If death does not occur, the patient begins to
show signs of clinical improvement. The blood
pressure begins to rise, the temperature returns to
normal and the urine secretion re-established. If
anuria persists, the patient may die of renal failure.

The classical form of severe cholera occurs in only

5-10 percent of cases. In the rest the disease tends
to be mild characterized by diarrhoea with or
without vomiting or marked dehydration. As a rule,
mild cases recover in 1-3 days
 Lab Diagnosis
WHO Standard case definition: A case of cholera
should be suspected when:
• in an area where the disease is not known to be
present, a patient aged 5 years or more develops
severe dehydration or dies from acute watery
diarrhoea;
• in an area where there is a cholera epidemic, a
patient aged 5 years or more develops acute watery
diarrhoea, with or without vomiting.
Laboratory methods of diagnosis are required to
confirm the diagnosis.

a) Collection of specimens:
The Sample should be collected before the
person is treated with antibiotics.
i) Stool: using rubber catheter or rectal swab

ii) Vomitus
b) Transportation
Stool collected should be transported in
sterilized 30ml capacity McCartney bottles
containing Alkaline peptone water or VR medium.
1ml of stool in 10 ml of transport media will
suffice.
Specimen collected by rectal swab should be
transported in alkaline peptone water or Cary-Blair
medium
c) Direct examination:
Dark field microscopy is used to view Vibrio
cholerae that evoke the image of shooting star in
dark sky.

Only a presumptive diagnosis can be made

because it is not reliable.
d) Culture:
About 0.5 to 1ml of specimen is inoculated
into Peptone Water Tellurite (PWT) medium for
enrichment and incubated for 4 to 6 hours at
37°C.
A loopful of the culture from the surface is
subcultured on Bile Salt Agar (BSA). After
overnight incubatiion the plates are screened
under oblique light illumination for vibrio
colonies.
Cultural characteristics:
Translucent, moist, raised, smooth and easily
emulsifiable colonies of about 1mm diameter is
seen.
The typical colonies are picked up and tested with:
i) gram stain and motility
ii) serological test: slide agglutination with anti
cholera diagnostic serum and with Inaba and Ogawa
antisera.
e) Biochemical tests: Cholera Red Reaction
Serologically positive colonies are
subcultured in one tube each of the sugar broths
(mannose, sucrose, arabinose) and a tube of
peptone water for the Cholera Red Reaction.
Production of acid in sucrose and mannose
but not arabinose is characteristic of V. cholerae
 Control of Cholera
“Guidelines for Cholera Control” by WHO

1) Verification of Diagnosis
-Investigation of all cases of diarrhoea for cholera
-Bacteriological diagnosis of cholera
 Control of Cholera
2) Notification
-Notify the local health authority
-Cholera is notifiable to WHO within 24 hours of
occurrence
-Number of cases and deaths reported daily and weekly
-Area is declared free of cholera when twice the
incubation period (10 days) elapsed since the death,
recovery or isolation of last case

3) Early case finding

-Aggressive search for cases in the community
 Control of cholera
4) Establishment of treatment centres

5)Rehydration therapy
-Mildly dehydrated patients (90%)- ORS at home
-Severely dehydrated- iv fluids at hospital or treatment centre

6) Adjuncts to therapy
-Antibiotics given after vomiting stopped
-Fluoroquinolone, Tetracycline, Azithromycine, Ampicillin
-No other medications
 Control of Cholera
7) Epidemiological investigations
-To define the extent of outbreak and identify modes of
transmission
-Effective and specific control measures can be applied
 Control of Cholera
8) Sanitation measures
Water Control
-

Boiling, Chlorination

- Excreta disposal
Provision of sanitary latrines
Handwashing with soap after defecation

-Food sanitation
Cooked hot food
Cleaning and drying of utensil after use
Housefly is a indicator of level of sanitation
 Control of Cholera
-Disinfection
Disinfection of patient’s clothes and personal items, latrine
Disinfectant with RW coefficient>5 like Cresol

9) Chemoprophylaxis
- Chemoprophylaxis of close household contacts
- Mass chemoprophylaxis not advised
- Tetracycline or Doxycycline
 Control of cholera
10) Vaccination
Oral Vaccines: Dukoral and Sanchol and mORCVAX

a) Dukoral
Monovalent
Based on formalin and heat killed whole cells of V. cholerae O1
plus recombinant cholera toxin B subunit
3 ml single dose vial with bicarbonate buffer
 Control of Cholera
Schedule and administration of Dukoral
Primary immunisation : 2 oral doses given >7 days but <6 weeks
Booster dose: After 2 years

For children 2-5 years: 3 doses >7 days but <6 weeks apart
Booster dose: 6 months

b) Sanchol and mORCVAX

2 liquid doses 14 days apart
Booster dose: 2 years
Based on serogroups O1 and O139
 Control Of Cholera
11) Health Education
ORS
Early reporting and prompt treatment
Food hygiene
Sanitary latrine and handwashing
Cooked hot foods and safe water
 Cholera control in nepal
• EDCD (Epidemiology and Disease Control
divison)
-Surveillance of Cholera among other
communicable diseases

EWARS: Early warning and reporting system

 EWARS
• Hospital based sentinel surveillance system
• 81 hospitals in 75 districts
• Weekly reporting of detailed line list of cases and
deaths (including 0) of 6 priority diseases
including cholera
• Immediate reporting (ASAP,<24 hours) of one
confirmed case of cholera
• EWARS news bulletin produced every Sunday
• Rapid response team for outbreaks
• EDCD
-Active surveillance in case of outbreak
- Water quality monitoring and surveillance
- Communicable disease research program

• WASH (Water, Sanitation and Hygeine)

 Cholera control in nepal
• Control of Diarrhoeal Disease
-Under CB-IMNCI
-Covers all 75 districts
-Includes children under 5 years
-Use of ORS and zinc in all cases of childhood diarrhoea
Ending Preventable Child Deaths from
Pneumonia and Diarrhea by 2025
The integrated Global Action Plan for Pneumonia and
Diarrhea(GAPPD)
 Specific Goals for 2025: Reduction in
< 5 year children
 Mortality from pneumonia to < 3 per 1000
live births.
 Incidence of severe pneumonia by 75%
compared to 2010 levels ()
 Incidence of severe diarrhea by 75%
compared to 2010 levels ()
 Global number of children stunted by 40%
compared to 2010 levels ()
 Coverage Targets: By the end of 2025

 90% full-dose coverage of each relevant

vaccine (with 80% coverage in each district)
 90% access to appropriate pneumonia and
diarrhea case management (with 80%
coverage in each district)
 At least 50% coverage of exclusive breast-
feeding during the first 6 months of life
 Virtual elimination of pediatric HIV
Coverage Targets: By the end of 2030

Universal Access in health care

facilities and home to-
 Basic drinking water
 Adequate sanitation (2030/2040)
 Hand washing facilities
 Clean and safe energy technologies
 Core Objectives
 To reduce the morbidity, mortality and
disability among newborns, infants and
children aged <5 yrs.
 To improve the nutritional status of children