Cholera

Cholera

Vaccine-Preventable Diseases 1
WHO Vaccine-Preventable Diseases Surveillance Standards
Surveillance Standards
 Cholera

This is a summary of the Global Task Force on Cholera Control's Interim Guidance on
Cholera Surveillance, available at http://www.who.int/cholera/task_force/GTFCC-
Guidance-cholera-surveillance.pdf?ua=1.

DISEASE AND VACCINE CHARACTERISTICS

Cholera is a diarrhoeal disease caused by toxigenic children < 5 years of age. Current estimates of cholera
serogroups of the bacterium Vibrio cholerae, which can cases range from 1.4 to 4 million, and estimated cholera
cause rapid dehydration and death. Cholera is closely deaths range from 21,000 to 143,000 (1). However,
associated with poverty, poor sanitation and lack of global burden of cholera is underestimated due to
clean drinking water. As such, the cholera burden is contributing factors such as low reporting, limited
concentrated in Africa and southern Asia, accounting epidemiological surveillance and lack of laboratory
for about 99% of worldwide cases. Cholera can be capacity.
endemic and cause epidemics. Cholera bacteria are
Two types of killed whole-cell oral cholera vaccines
spread by direct faecal-oral contamination or ingestion
are available: a monovalent (O1) vaccine with a
of contaminated water or food. The incubation period
recombinant B subunit of the cholera toxin, and a
is less than 24 hours to 5 days. Only up to 25% of
bivalent (O1 and O139) without the B subunit. The
infected persons become symptomatic; of these, 10–20%
vaccines are given as two- or three-dose regimens.
experience severe disease. Severe disease manifests as
Neither vaccine is recommended for infants. Cholera
acute, profuse watery diarrhoea (“rice water stools”),
vaccines are recommended in endemic settings, during
usually with vomiting. This leads to rapid dehydration,
cholera outbreaks and in humanitarian crises with risk
which can result in hypotensive shock, renal failure and
of cholera. WHO has maintained a stockpile of cholera
death within hours of onset.
vaccine since 2013 to be used in these situations, upon
The cholera case fatality rate should be below 1% request of the country. Cholera vaccines should always
where access to care with proper rehydration services be used in conjunction with other cholera prevention
(oral and/or intravenous) is available, but it may reach and control strategies (see Box 1).
5% in the most vulnerable settings. Cholera affects all
age groups, although half of the cholera deaths are in

BOX
Prevention of cholera through non-vaccine strategies
1
Vaccination is not the primary preventive strategy for cholera. The mainstay
of cholera prevention and control is access to clean potable water, adequate
sanitation, and promotion of good water, sanitation and hygiene (WASH)
practices. Other preventive efforts should include promotion of hand-washing
and safe food handling practices. Moreover, cholera can be effectively treated
with rehydration, and resources should be devoted to improving access to
effective care. Cholera vaccination can be complementary to these activities,
implemented in the short-to-medium term while access to primary prevention
through WASH and other control measures improves globally (2).

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WHO Vaccine-Preventable Diseases Surveillance Standards
 RATIONALE AND OBJECTIVES OF SURVEILLANCE

The objectives of cholera surveillance are to: hygiene education in the community, immunization
of at-risk population, and adequate and timely access
hh detect and characterize cholera outbreaks
to patient care
hh identify high-risk areas and vulnerable populations
to guide preventive and control measures, including hh monitor disease occurrence and epidemiology
better access to safe water and sanitation, health and hh estimate cholera disease burden.

TYPES OF SURVEILLANCE RECOMMENDED

MINIMAL SURVEILLANCE surveillance is facility-based; health facilities keep

Event-based surveillance is the minimal surveillance line lists of suspected cholera cases (see definition
standard (3) when the objective is to detect cholera of suspected cholera case below). Indicator-based
outbreaks. Event-based surveillance is not based on surveillance can take place solely in sentinel sites in
standard case definitions to detect cases, but rather on areas of risk, or could potentially take place nationwide.
unstructured descriptions, rumours and reports about Laboratory testing is done to confirm cholera on
any event that might indicate a cholera outbreak. suspected cases. This type of indicator-based surveillance
Sources of information include official sources can detect outbreaks as well as provide information
(Ministries of Health, institutes, agencies, international on cholera epidemiology and burden. While it is
organizations, etc.), formal sources (health facilities, recommended that case-based data be transmitted to
hospitals, laboratories, health care workers, community higher levels, lower levels can choose to aggregate the
health workers, non-governmental organizations, etc.) results and report the number of cases in their integrated
and informal sources (press, radio, TV, blogs, social aggregate diseases surveillance system, like Integrated
media, rumours from the community, reports, etc.). Disease and Surveillance Response (IDSR).
Follow up on reported events within 24 hours and take
Ideally, indicator-based and event-based cholera
appropriate measures to confirm or rule out a cholera
surveillance are integrated to most efficiently detect and
outbreak.
characterize cholera outbreaks and disease.

ENHANCED SURVEILLANCE
Indicator-based surveillance is the routine collection
of surveillance data on individual cases that meet
the suspected cholera case definition. For cholera,

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 Cholera

CASE DEFINITIONS AND FINAL CLASSIFICATION

SUSPECTED CASE DEFINITION FOR CASE FINDING area have cholera, with only periodic laboratory testing
In areas where a cholera outbreak has not been declared, to confirm that cholera transmission persists and thus
a suspected case is any patient aged ≥ 2 years who has the outbreak is ongoing.
acute watery diarrhoea and severe dehydration or died
Certain public health responses are triggered by a
from acute watery diarrhoea. (Acute watery diarrhoea is
cholera alert. A cholera alert is defined by the detection
characterized by three or more loose or watery, non-
of any of the following:
bloody stools within a 24-hour period.) In areas where
a cholera outbreak is declared, a suspected case is any hh two or more people ≥ 2 years of age linked by time
person presenting with or dying from acute watery and place (from the same area within one week of
diarrhoea. one another) with acute watery diarrhoea and severe
dehydration, or dying from acute watery diarrhoea
CONFIRMED CHOLERA CASE hh one death from severe acute watery diarrhoea in a
A confirmed cholera case is any suspected case in which person ≥ 5 years of age
Vibrio cholerae O1 or O139 is confirmed by culture or
polymerase chain reaction (PCR) test. In countries hh one case of acute watery diarrhoea testing positive
for cholera by rapid diagnostic test (RDT) in an area
where cholera is not present or has been eliminated,
that has not yet detected a confirmed case of cholera,
the case is confirmed if Vibrio cholerae O1 or O139 is
including those at risk for extension from a current
toxigenic. After a cholera outbreak has been identified,
outbreak.
assume that all cases of acute watery diarrhoea in the

CASE INVESTIGATION

Any cholera alert reported through event-based or placed under contact precautions (strict handwashing)
indicator-based surveillance should trigger a field to prevent spread of cholera. Countries can choose to
investigation to confirm or rule out the outbreak. Stool implement an active case search for other suspected
samples from suspected patients should be collected cholera cases in the community if resources allow. Early
for laboratory confirmation, which will then serve as in the course of an outbreak, case investigations can be
the basis for outbreak declaration. Ideally, a case’s stool done to identify risk factors and sources of transmission
is tested with a cholera RDT. If positive, the sample is like water sources or food, which might be amenable to
sent to a laboratory able to conduct confirmatory testing interventions.
(culture or PCR). If a patient is in a health facility,
the patient should be isolated from other patients and

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WHO Vaccine-Preventable Diseases Surveillance Standards
 SPECIMEN COLLECTION

Accurate and reliable test results depend on having a Other considerations for storage of stool samples for
sample that has been collected, stored and transported culture include the following:
correctly (4). The national reference laboratory should
hh avoid cold storage (2–8°C) of the samples, as it can
standardize methods for collection and transport of
greatly decrease the populations of Vibrio cholerae
stool samples. The methods should be documented and
available to staff or health care providers who collect, hh do not allow specimen to dry
package and ship samples.
hh add small amount of normal saline if necessary

SPECIMEN TYPES
hh transport in a well-marked, leak-proof container at
room temperature.
Faecal specimens (liquid stool or rectal swabs) are
used to diagnose cholera. Faecal specimens should be
collected in the early stage of the illness, when pathogens For culture, the sample must not be allowed to dry
are usually present in the stool in highest numbers out. However, for DNA detection by PCR, dry filter
(ideally within the first four days of illness), and before papers can be used for transport of faecal specimens.
antibiotic therapy has been started. Do not delay patient All specimens should be accompanied by a laboratory
rehydration treatment in order to take a specimen. request form containing at minimum the following
Specimens may be collected after rehydration has begun. information:

hh patient name or initials

STORAGE AND TRANSPORT
Place the specimen in a clean, appropriately labelled, hh age
leak-proof container and transport to the laboratory at hh place of residence
room temperature within two hours. If a container must
be cleaned, avoid the use of any solution that contains
hh date and time of collection
chlorine. If there will be more than a two-hour delay, hh symptoms
place a stool-soaked swab into Cary-Blair transport
hh date of onset of symptoms
medium. If kept sterile and properly sealed, Cary-Blair
transport medium is stable in storage for several months hh type of testing requested (culture, PCR or both).
and does not require refrigeration (before use and once
inoculated). If Cary-Blair transport medium is not
available and the specimen will not reach the laboratory
within two hours, another possible option is to preserve
and transport liquid stool samples on a filter paper
kept in a moist environment. To do so, dip a blotting
paper disc into the liquid stool and place in a screw-
cap microtube with two or three drops of normal saline
solution to stop the sample from drying out.

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LABORATORY TESTING

The objectives of the laboratory diagnosis of cholera False negatives using RDTs or culture can occur if
include confirming alerts and declaring outbreaks, specimens are collected:
monitoring antibiotic susceptibility, characterizing the
hh in receptacles containing chlorine residues
circulating strains, identifying changes in the virulence,
supporting epidemiologic investigations and declaring hh after initiating antibiotic therapy
the end of an outbreak.
hh in case of poor sampling or handling practices of the
Stool culture is the gold standard for testing for Vibrio specimen, such as a long delay.
cholerae but requires selective media; thiosulfate- Stool may be tested for other enteric pathogens, but the
citrate-bile salts agar (TCBS) is ideal for isolation requirements of transport and testing will differ from the
and identification. Cholera isolation is important requirements for cholera testing and should be planned
for characterization of antibiotic susceptibility and for accordingly.
subtyping, usually done through the use of antisera.
At least one laboratory in the country should be
PCR can be used in place of culture to detect toxigenic operational and capable of isolating and identifying
Vibrio cholerae. However, while it is sensitive and specific Vibrio cholerae by culture or PCR if available and testing
for this bacteria, it cannot provide information on for antibiotic susceptibility. The designated reference
antibiotic susceptibility. laboratory should be able to provide transport media
Cholera RDTs such as dipsticks are based on and reagents, train technicians and monitor the quality
immunochromatographic tests and are intended for use of examinations. While there is no global laboratory
at primary health care sites for the following purposes: network for cholera, there are WHO collaborating
centres and regional reference labs that can provide
hh surveillance support in laboratory diagnostics for cholera. Establish
hh early outbreak detection collaboration with these international laboratories that
can perform quality assurance, provide training and
hh tool for initial alerts
conduct molecular testing for characterization and
hh outbreak monitoring, including potential new foci genotyping of circulating Vibrio cholerae strains.
and seasonal peaks in highly endemic areas.

Cholera RDTs do not replace stool culture or PCR to

confirm cholera and should not be used for individual
diagnosis. However, culture confirmation is rarely
accessible in peripheral healthcare facilities where most
of the cholera patients present. The use of cholera RDTs
can improve the reliability of cholera alerts by permitting
the triage of specimens while waiting for culture or
PCR confirmation (5). Given the high sensitivity of
RDTs, countries can choose to send stool samples for
confirmatory testing from only those patients who
screen positive on the RDT. Culture results should be
available within a maximum of two to four days after the
specimen arrives at the laboratory.

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WHO Vaccine-Preventable Diseases Surveillance Standards
 DATA COLLECTION, REPORTING AND USE

RECOMMENDED DATA ELEMENTS REPORTING REQUIREMENTS AND

Each health facility should create and regularly RECOMMENDATIONS
update a line list register of cases that contains at least In a previously unaffected area or area with no recent
demographic, clinical and laboratory information for reported cases, any cholera alert should be immediately
each case, as follows: reported (within 24 hours) to the next higher level
health authorities (provincial or national), so they can
hh Unique case identifier conduct field investigations to confirm and declare the
hh Age in years or age in months outbreak.

hh Sex In an area where a cholera outbreak is declared, report

the number of cases and deaths – both registered at the
hh Place of residence to the smallest administrative area
health facility and occurring in the community – daily or
(GPS is ideal)
weekly to monitor the disease incidence, mortality, case
hh Signs and symptoms fatality ratio and any prevention or case management
hh Date of symptom onset interventions.

hh Hospitalization status In an area where cholera disease is endemic, the number

of cases and deaths – both registered at the health
hh Level of dehydration (none, some, severe) or facility and occurring in the community – must be
treatment plan (A, B, C) (6)
reported weekly (or monthly if the number of cases is
hh Outcome (survived or died) low) in order to estimate basic surveillance indicators
(incidence rate, case fatality ratio and attack rates) and
hh Laboratory results
describe the situation in terms of time, place and person.
If cholera surveillance is part of IDSR, follow the IDSR
The following additional case-based data may also be reporting schedule.
collected:
Reporting for cholera can be either case-based or
hh Risk factors aggregate based on the resources in the country. WHO
does not require that cholera cases be reported through
hh Activity or profession
International Health Regulations (IHR) unless a
hh Displaced or living in camps cholera outbreak is deemed a public health emergency
hh Cholera vaccination status, including date vaccinated of international concern. Cholera cases are not routinely
and type of vaccine collected through the WHO/UNICEF Joint Reporting
Form ( JRF).
hh Pregnancy status

Sample data collection tools can be found elsewhere,

such as the Interim Guidance Document on Cholera
Surveillance (3). If reporting is aggregate, transmit the
following data to higher levels: age (< 5 years of age;
≥ 5 years of age), district, month and year of onset and
outcome.

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 Cholera

RECOMMENDED DATA ANALYSES See the Interim Guidance Document on Cholera

The following data analysis should be completed: Surveillance (3) for details on how to calculate the
incidence, attack rates and case-fatality ratios.
hh the aggregated number of confirmed cholera cases
and deaths – both registered at the health facility
and occurring in the community – by age group USING DATA FOR DECISION-MAKING

(< 5 years of age; ≥ 5 years of age) Analysis should be used to monitor facility-level
performance (striving for a low case fatality ratio), as
hh incidence and attack rates, overall and stratified by well as to monitor trends, identify populations at risk
age group and location
and initiate or adjust response interventions.
hh case fatality ratios by age group and by facility
hh proportion of cases that have received vaccine
(if vaccine introduced in area of outbreak).

SURVEILLANCE PERFORMANCE INDICATORS

Regular monitoring of surveillance indicators might surveillance indicators to monitor are listed in the
identify specific areas of the surveillance and reporting table below, and may be modified based on the type of
system that need improvement. Some suggested surveillance conducted.

TABLE
Recommended surveillance performance indicators
1
HOW TO CALCULATE
SURVEILLANCE
INDICATOR TARGET (NUMERATOR / COMMENTS
ATTRIBUTE
DENOMINATOR)

Percentage of ≥ 80% # sites reporting cholera

designated sites data / # designated
COMPLETENESS
reporting cholera reporting sites for cholera
OF REPORTING
data, even in the surveillance x 100 (for
absence of cases given time period)

Percentage of ≥ 80% # of surveillance At each level reports should be

surveillance units units in the country received on or before the requested
reporting cholera reporting cholera data date.
TIMELINESS OF
data to the by the deadline / # of
REPORTING
national level on surveillance units in the
time even in the country x 100
absence of cases

Percentage of ≥ 80% # of cholera alerts for

all cholera alerts which an investigation is
TIMELINESS OF
that have had initiated within 48 hours
INVESTIGATION
an investigation of notification / # of
(OF ALERTS)
initiated within 48 suspected cholera alerts
hours of notification x 100

Percentage of ≥ 80% # of specimens with results

TIMELINESS
specimens with reported within 4 days of
OF REPORTING
results reported specimen receipt / # of
LABORATORY
within 4 days of specimens received x 100
RESULTS
receipt of specimen

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WHO Vaccine-Preventable Diseases Surveillance Standards
 CLINICAL CASE MANAGEMENT

Effective treatment for cholera exists and should be susceptibility profile should be provided to clinicians to
initiated as soon as possible. The mainstay of cholera guide case management and treatment of patients who
treatment is rehydration. Treatment depends on severity require antibiotics. Patients should be isolated from
of illness and level of dehydration. Severe cases need other patients and placed under contact precautions
intravenous rehydration and antibiotics. Milder cases to prevent spread. Further details can be found in
can be treated with an oral rehydration solution; zinc Cholera Outbreak (7) at http://www.who.int/cholera/
supplementation should also be given to children < 5 publications/final%20outbreak%20booklet%20260105-
years of age. Information regarding the antimicrobial OMS.pdf.

CONTACT TRACING AND MANAGEMENT

Contact tracing is not currently a strategy recommended as part of cholera control.

SURVEILLANCE, INVESTIGATION AND RESPONSE

IN OUTBREAK SETTINGS

DEFINITION OF AN OUTBREAK to increase the probability of identifying the outbreak

A cholera outbreak is defined by the occurrence of at as a true alert. If the RDT is negative, cholera can be
least one confirmed case of cholera and evidence of local ruled out. If at least one sample tests positive by culture
transmission (3). Outbreaks can also occur in areas with or PCR by the reference laboratory, then declare the
sustained year-round transmission. These outbreaks are outbreak and immediately implement control measures
defined by an unexpected increase in the magnitude or in the affected area. Once Vibrio cholerae is confirmed
timing of suspected cases over two consecutive weeks, by the laboratory and the outbreak is declared, there is
with some cases being confirmed by the laboratory. no need to confirm all suspected cases. All individuals
Investigate and respond to such increases appropriately with acute watery diarrhoea should be registered and
through additional outbreak response and control reported as suspected cholera cases. For each new district
measures. or region affected by the outbreak, confirm the outbreak
with laboratory confirmation by culture or PCR of
CHANGES TO SURVEILLANCE DURING AN suspected cases.
OUTBREAK
Do periodical sampling and testing on suspected cases
If the existing cholera surveillance is case-based, shift
to monitor the outbreak, determine the antibiotic
to aggregate reporting during an outbreak. Not all acute
susceptibility profile and carry out continuous
watery diarrhoea cases need laboratory confirmation in
monitoring of strains. If you are using RDTs, prioritize
the setting of an outbreak.
RDT-positive samples for transport to the laboratory.
RDT-negative samples may also be sent if no positive
LABORATORY TESTING IN THE SETTING OF AN
samples are available. The number of samples collected
OUTBREAK
and tested depends on the laboratory capacity and
Rapid confirmation of cholera is important in the setting
the extent of the outbreak. Ideally, a minimum of five
of a potential outbreak. If RDTs are available, send
samples from suspected cases per week per health
the RDT positive samples to the reference laboratory

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 Cholera

facility should be sent for laboratory confirmation and quality, and promoting hygiene conditions and practices
antimicrobial susceptibility testing. Ideally, pre-select (7). Good hygiene practices include hand-washing, safe
samples based on RDT results. When there is a large preparation of food, safe burials, and improved sanitation
or nationwide outbreak or when lab capacity is limited, and excreta disposal.
consider designating a number of Cholera Treatment
Consider the use of oral cholera vaccine as part of
Centres, which represent different demographic and
a reactive campaign. The use of the vaccine should
geographic populations, for collection and shipment
complement other control strategies, such as WASH
of samples for testing. When the number of suspected
and community mobilization. Cholera vaccination can
cases in the epidemic area significantly declines and
help prevent the spread of current outbreaks to new
all samples from all cases of acute watery diarrhoea
areas (7). Make a decision to implement vaccination
test negative by RDT, culture or PCR for at least two
only after a thorough investigation of the current and
weeks, the outbreak can be considered ended. About
historical epidemiological situation. Clearly identify the
20 stool samples should be tested negative to declare
targeted geographical areas and populations, and assess
the outbreak over (7), at which point the laboratory
the feasibility of organizing a vaccination campaign
can resume testing of suspected case as part of routine
given the local infrastructure and other factors. Mass
surveillance.
vaccination with a single dose for short-term protection
Of note, the first few suspected cases appearing in a new is the preferred strategy for reactive campaigns during
district should be culture confirmed to detect outbreak outbreaks to help control the outbreak until long-term
extension. WASH can be established (2). If the risk of cholera
persists, an additional vaccination may be needed to
PUBLIC HEALTH RESPONSE ensure longer-term protection.
Implement control measures rapidly as soon as there is
indication of a cholera outbreak, even before laboratory SPECIAL ASPECTS OF INVESTIGATION
confirmation. Cholera control measures are aimed at In the beginning of an outbreak, a field epidemiological
reducing mortality and the spread of the disease. These and environmental investigation on the first cases can
measures include setting up cholera treatment units and be useful to explore the risk factors and exposures to
oral rehydration points, ensuring early detection and identify the source of contamination. When available,
transfer of severe cases, training health professionals, spatial data collection using GPS will support
applying standard case-management protocols, the outbreak investigation and help describe the
strengthening epidemiological and laboratory capacity geographical pattern. If possible, record inhabited areas,
for surveillance, ensuring access to water in quantity and water sources and any other relevant features.

SPECIAL CONSIDERATIONS FOR CHOLERA SURVEILLANCE

SURVEILLANCE IN EMERGENCY SETTINGS ENVIRONMENTAL TESTING

Because of the increased risk of cholera outbreaks Given that cholera is primarily a waterborne disease,
in humanitarian and complex emergencies, consider monitoring the presence of Vibrio cholerae in specific
establishing prospective cholera surveillance to environmental water sources may identify sources or
detect outbreaks early. If a risk assessment in such vehicles of infection and aid with the early detection of
settings shows an increased risk of cholera, consider cholera transmission in some areas (3).
vaccination with oral cholera vaccine as an additional
preparedness measure for outbreak prevention when
local infrastructure allows, even if there is not a current
outbreak.

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 REFERENCES

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ADDITIONAL REFERENCES
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