WHO Technical Working Group

on creation of an oral cholera

vaccine stockpile

Meeting report
Geneva, 26–27 April 2012

Pandemic and Epidemic Diseases

Health Security and Environment

Acknowledgements
This meeting was a collaborative effort led by the Control of Epidemic Diseases (CED) Unit
in the Department of Pandemic and Epidemic Diseases (PED), of the Health Security and
Environment (HSE) cluster at World Health Organization (WHO) headquarters.

Significant input was provided throughout by members of the Technical Working Group, as
well as by colleagues working in the WHO Regional Offices and other departments at WHO
headquarters. CED gratefully acknowledges this collaboration as well as the significant
contribution of Dr Sarah Ramsay who served as the rapporteur of the meeting and wrote and
finalised the report.

© World Health Organization 2012

All rights reserved.

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not necessarily represent the decisions or the policies of the World Health Organization.

WHO/HSE/PED/2012.2
Meeting report of the WHO Technical
Working Group on creation of an oral
cholera vaccine stockpile
Geneva, 26–27 April 2012

Contents
Executive summary ............................................................................................................... 1

1. Introduction....................................................................................................................... 5

2. Meeting background, objectives, and process .................................................................... 5

3. Overarching principles ...................................................................................................... 7

4. Criteria for the OCV to be stockpiled ................................................................................ 7

5. Epidemiological criteria for OCV stockpile use ............................................................... 13

6. Global governance of the OCV stockpile ......................................................................... 17

7. Working mechanism of the OCV stockpile ...................................................................... 21

8. Procurement of OCV for a stockpile ................................................................................ 22

9. Evaluation and external review of OCV stockpile............................................................ 24

10. Next steps and timeline ................................................................................................. 25

11. References..................................................................................................................... 27

12. Annex I: List of participants .......................................................................................... 29

13. Annex II: Meeting agenda ............................................................................................. 33

Tables:
Table 1: Criteria for candidate stockpile oral cholera vaccines............................................. 11
Table 2: Epidemiological and demographic considerations for OCV stockpile deployment . 15
 1

Executive summary
The global burden of cholera is unknown, however it is estimated that there are 1.4–4.3
million cholera cases and 28 000–142 000 cholera deaths each year. Two large national
cholera epidemics in Zimbabwe and Haiti, which resulted in thousands of cases and deaths,
have focused the world’s attention in recent years on the need not only to control endemic
disease but also to put in place improved epidemic cholera preparedness and response
measures.

Effective cholera prevention and treatment regimens are well established, yet cholera remains
poorly controlled in both outbreak and endemic contexts. The occurrence of cholera today
reflects weaknesses of water and sanitation programmes, limitations of the surveillance
systems for the early detection and monitoring of epidemics, and lack of access to timely
health care for patients.

In view of this situation, the 64th World Health Assembly in 2011 called for an integrated,
comprehensive strategy of cholera prevention and control. WHA Resolution 64.15 included
the consideration of the use of oral cholera vaccines (OCV) “where appropriate, in
conjunction with other recommended prevention and control methods and not as a substitute
for such methods”. This consideration was taken forward at a September 2011 consultation,
which noted that an OCV stockpile for outbreak control could be initiated in the near future.

This Technical Working Group was convened to develop an OCV stockpile implementation
framework. Participants advised on: the criteria for choice of stockpiled vaccine and its
deployment; the appropriate size of an OCV stockpile; the managing partnership and
evaluation processes required; the decision-making procedure and operational issues; and the
financing mechanism.

Below are the key points that summarize the findings for each of the numbered sections of
the report.

1.1: Vaccination has a role in prevention and control of cholera outbreaks together with
timely treatment, access to potable water and adequate sanitation, and community
involvement, all of which must be supported by effective epidemiological surveillance.

2.1: The focus of this Working Group was to advise the creation of an OCV stockpile
specifically to respond to outbreaks, with the understanding that guidance on other cholera
 2

outbreak prevention and control measures already exists and the introduction of cholera
vaccines in routine immunization programmes should be dealt with separately.

2.2: Creation and use of the OCV stockpile should be guided by epidemiological, technical,
and operational evidence, some of which remains incomplete and must be consolidated as
experience is gained.

3.1: Establishment of an OCV stockpile should not detract attention from the key established
responses to cholera outbreaks:

• Detection, diagnosis, and treatment of cases with oral rehydration and antibiotic
treatment;

• Establishment of a safe water supply;

• Implementation of adequate waste disposal, sanitation, and hygiene; and

• Communication and social mobilization.

3.2: Creation of an initial, necessarily small, OCV stockpile and its use will not in itself
constitute sufficient preparedness for a large and/or sustained cholera epidemic.

4.1: The Working Group agreed on a matrix of criteria to guide the choice of vaccine(s) to be
stockpiled. OCV characteristics that should guide the development of new vaccines were also
outlined.

5.1: The Working Group agreed a set of epidemiological criteria that should inform a
decision to release stockpile vaccine in response to an outbreak.

5.2: The Working Group agreed that requests for use of OCV from the stockpile in
humanitarian emergencies could be considered if vaccine supply from standard sources is not
readily available. Emergency response funds should be used to replenish the vaccine used
from the stockpile.

6.1: The International Coordinating Group (ICG) decision-making body comprising MSF,
IFRC, UNICEF, and WHO that oversees the meningococcal and yellow fever vaccine
stockpiles should extend its mandate to include OCV. This body is charged with developing
its own terms of reference and will require funding to cover the added operational costs.
Criteria for any additional members were defined. The OCV ICG should be nested within a
 3

wider group of organizations (e.g. technical, commercial, civil society, funding) that can
inform the partnership on their specific areas of expertise.

6.2: Submission of a vaccine request may be made by any national or international

organization. On receipt of such a request, the ICG should make a decision within 48 hours.

6.3: The OCV stockpile vaccine should be targeted at epidemics in those countries where
cholera is going to cause a significant burden. Participants agreed that the OCV stockpile
vaccine should be targeted at epidemics in low-income countries.

7.1: The OCV stockpile should initially comprise two million doses per year.

7.2: Storage of stockpile vaccine should be the responsibility of the manufacturer. The
stockpile should be maintained on a rotating stock basis.

7.3: Initial donor contributions should be sought to fund vaccine procurement, country
preparedness, and planned operational costs for the first 2-3 years based on the extensive
experience of the ICG. A revolving fund should be established to assure longer-term financial
stability.

8.1: A Procurement Reference Group should be established by the UNICEF Supply Division
(UNICEF/SD) to advise on technical issues regarding vaccine and stockpile specifications. A
reserved rather than prepaid stockpile is preferred.

9.1: A rigorous system of short- and longer-term monitoring and evaluation should be
embedded within the OCV stockpile mechanism. WHO should establish a stockpile
evaluation group to define and implement the detailed monitoring required. As experience
and data accrue, the results of this evaluation should enable continuous improvement in the
structure and functioning of the stockpile.

The Working Group agreed next steps and a timeline for action during 2012, as outlined in
section 10. These are summarized below.

WHO will:

• Recruit ICG focal points for cholera stockpile from partner institutions and agree on
terms of reference (July).
 4

• Advocate for and seek financial support and prepare and submit proposals to: the
European Union, the Bill & Melinda Gates Foundation, GAVI, the United Kingdom
Department for International Development, and the United States Agency for
International Development (ongoing).

• Inform WHO Headquarters, Regional Offices, Member States, and partners about the
planned availability of OCV stockpile and disseminate epidemiological and
operational criteria (October).

• Convene OCV stockpile working group to define a template for deployment

evaluation (October).

• Liaise with SAGE Vaccination in Emergencies Working Group to ensure that the
consensus of this meeting is compatible with the development of the SAGE
Framework (June).

• Meet vaccine producers to discuss production capacity, vaccine presentation, storage

capacity, etc (September).

WHO and UNICEF/SD will:

• Develop a strategy that includes milestones for different procurement processes

(October).

• Convene a Procurement Reference Group to evaluate the bids. This will only be
possible once finance is in place.
 5

1. Introduction
A reduction in the contribution of cholera to the burden of disease in developing countries is
a priority for the global health community. In endemic countries, an estimated 1.4 billion
people are at risk and worldwide the reported number of cases and deaths has been increasing
since 2000. It is widely acknowledged that under-reporting and weak surveillance mean that
the true burden is unknown, however it is estimated that there are 1.4–4.3 million cholera
cases and 28 000–142 000 cholera deaths annually. In recent years, two large national cholera
epidemics in Zimbabwe and Haiti, which resulted in thousands of cases and deaths, focused
the world’s attention on the need not only to control endemic disease but also to put in place
improved epidemic cholera preparedness and response measures.

Cholera prevention and treatment regimens that do not include vaccination are well
established and mostly effective, yet cholera remains poorly controlled in both outbreak and
endemic contexts. The emergence and prolonged occurrence of cholera reflects the
weaknesses of water and sanitation programmes, the limitations of the surveillance systems
for the early detection and monitoring of epidemics, and the lack of access to timely health
care for patients.

In view of this situation, the 64th World Health Assembly in 2011 called for an integrated,
comprehensive strategy of cholera prevention and control.1 WHA resolution 64.15 included
the consideration of the use of cholera vaccines “where appropriate, in conjunction with other
recommended prevention and control methods and not as a substitute for such methods”. This
consideration was taken forward in September 2011 at a consultation convened by WHO and
organized jointly by the Initiative for Vaccine Research (IVR) and the Global Task Force on
Cholera Control, as part of a project funded by the Bill & Melinda Gates Foundation.

Key point 1.1: Vaccination has a role in prevention and control of cholera
outbreaks together with timely treatment, access to potable water and adequate
sanitation, and community involvement, all of which must be supported by
effective epidemiological surveillance.

2. Meeting background, objectives, and process

The September 2011 consultation emphasised the importance of developing an OCV action
plan as soon as possible.2 It outlined two approaches: (1) countries should consider vaccine
 6

introduction through their national immunization programmes to control endemic disease; (2)
for outbreak control, a stockpile could be initiated in the near future.

The current technical consultation concerned the second recommended approach, i.e. the
creation of an OCV stockpile intended for use in epidemic control. The Working Group
meeting’s objectives were built on the following agreed premises:

Key point 2.1: The focus of this Working Group was to advise the creation of an
OCV stockpile specifically to respond to outbreaks with the understanding that
guidance on other cholera outbreak prevention and control measures already
exists and the introduction of cholera vaccines in routine immunization
programmes should be dealt with separately.

Key point 2.2: Creation and use of the OCV stockpile should be guided by
epidemiological, technical, and operational evidence, some of which remains
incomplete and must be consolidated as experience is gained.

Accordingly, the Working Group was invited to address the following questions:

• What criteria should be applied to the choice of cholera vaccine(s) to be stockpiled?

• What criteria should be set for determining when to vaccinate against cholera in
outbreak situations and how can vaccination be best targeted?
• What should be the optimal size of a short-term cholera vaccine stockpile, based on
current production capacity?
• What collaborative partnership and mechanism of oversight should be set in motion to
ensure the appropriate use of the stockpile?
• What financing mechanism will guarantee the launch and sustainability of the
stockpile?
• What monitoring and evaluation mechanisms should be applied to ascertain that
experience is documented and knowledge gaps filled?

The Chair noted that not all the issues and questions above might be adequately debated and
answered by the meeting and that it might be necessary to refer or defer some inquiries,
provided that such additional investigation did not delay creation of the stockpile.
 7

The Chair invited participants and observers to introduce themselves and declare any interest
that may be perceived to be in conflict with the objectivity of their contribution. The Chair
outlined the process by which the meeting would be conducted. During the majority of the
meeting, which would be open to all members of the Working Group and observers,
discussions on key issues would take the form of suggestions only. Presentations at the
meeting (see Annex II) would stimulate discussion and debate. Development of consensus
points would be informed by these discussions but would take place separately in closed
sessions, from which participants with actual or perceived conflicts of interest would be
excluded. The participants assented to this procedure and, to avoid any perception of
potential conflict of interest, three invited participants agreed to absent themselves from
sessions during which consensus decisions would be made, see Annex I for details.

It was agreed that comments made by participants would not be attributed. It was noted that
one person would join a segment of the meeting by telephone.

3. Overarching principles
There were two recurring points of importance that the Working Group noted should be
emphasised as overarching principles.

Key point 3.1: Establishment of an OCV stockpile should not detract attention
from the key established responses to cholera outbreaks:
o Detection, diagnosis, and treatment of cases with oral rehydration and
antibiotic treatment;
o Establishment of a safe water supply;
o Implementation of adequate waste disposal and sanitation; and
o Communication and social mobilization.

Key point 3.2: Creation of an initial, necessarily small, OCV stockpile and its use
will not in itself constitute sufficient preparedness for a large and/or sustained
cholera epidemic.

4. Criteria for the OCV to be stockpiled

The Working Group was asked to advise on the characteristics that would be essential for the
vaccine selected to be held in the stockpile. Two OCVs are currently WHO-prequalified; both
 8

are whole-cell, killed vaccines and are marketed under the names Dukoral® and ShancholTM;
WHO is also aware of six cholera vaccines that are currently in development2 that might be
considered in the future for the stockpile.

For the creation of an immediate stockpile, both prequalified OCVs are under consideration.
There is no known direct comparison of the two vaccines’ efficacies published or in progress.
Their key attributes are briefly outlined below.

Dukoral® (Crucell Ltd)

Each dose of Dukoral® consists of recombinant cholera toxin B subunit and inactivated whole
cells of the classic and El Tor biotypes of Vibrio cholerae O1, serotypes Inaba and Ogawa.
Dukoral® has been prequalified by WHO since 2001. The vaccine needs to be administered
with buffer to neutralize stomach acid and protect the cholera toxin that requires 75–150 mL
of clean water for preparation. Dukoral® is given in 2 doses 1–6 weeks apart in people aged
≥6 years, with a single booster dose after 2 years. Three doses are required for children aged
2–5 years, with a booster dose every 6 months. The vaccine is not licensed for use in children
younger than 2 years.

This vaccine and its precursor, which contained chemically purified rather than recombinant
cholera toxin B subunit, have been shown to be safe and protective. The earliest trial of
Dukoral® precursor in Bangladesh compared whole-cell vaccine or precursor Dukoral®
against placebo. At 6 months precursor Dukoral® exhibited 85% protective efficacy in all age
groups against V cholerae O1; whole cell vaccine alone was 58% protective.3 A subsequent
analysis of the data from this study indicated that a herd immunity effect occurred in areas
where vaccine coverage achieved levels of more than 50%.4

Use of Dukoral® in a non-endemic setting was assessed in a trial during an outbreak of

cholera in Peruvian military personnel. Several weeks after vaccination, the protective
efficacy against cholera in recipients of 2 doses of vaccine was 86%.5

Concerns that high rates of HIV infection might compromise the level of protection made
possible by cholera vaccination were addressed by a case-control study during an outbreak of
El Tor Ogawa cholera in urban Mozambique following a mass immunization campaign with
Dukoral®. The HIV seroprevalence in the study population was 20–30%. 72% of the 19 550
target population received 1 dose of vaccine and 57% received both doses. Per-protocol
 9

analysis indicated a protective efficacy of 84%. Intention-to-vaccinate analysis indicated a

vaccine effectiveness of 78%.6

Shanchol™ (Shantha Biotechnics)

Each dose of Shanchol™ contains inactivated V cholerae O1 cells representing the El Tor
and classical biotypes and the Inaba and Ogawa serotypes, as well as serogroup O139 cells.
WHO prequalification of the vaccine was granted in September 2011.

Shanchol™ is ready for use and does not require buffer. The vaccine is given in 2 doses 2
weeks apart in people aged ≥1 year. The vaccine is not licensed for use in children aged <1
year.

The vaccine was assessed in a cluster-randomized, controlled field trial that enrolled more
than 69 000 individuals aged 1 year and older living in urban slums of Kolkata, India.
Shanchol™ provided 67% protection against clinically significant V cholerae O1 cholera for
2 years.7 At further follow-up, the vaccinated population experienced 66% protection against
all episodes of cholera during the 3 years after vaccination, and 65% protection against
episodes occurring during the third year.8 Follow-up of the study population will continue to
5 years.

Discussion and rationale for advice

As a template for their deliberations, this Working Group used the criteria for vaccines for
use in cholera-affected countries set by the ad hoc Cholera Vaccine Working Group of the
Strategic Advisory Group of Experts (SAGE) on Immunization in 2009.9 The 2009 ad hoc
group recommended that cholera vaccines must, at a minimum, protect against both Ogawa
and Inaba serotypes of V cholerae O1 El Tor – and should provide at least 50% sustained
protection for 2 years in cholera-affected countries. The vaccines should be safe and usable in
people as young as 2 years old, as well as in pregnant women and HIV-infected and other
immunocompromised individuals.

The Working Group decided that it would be useful to modify the matrix produced by the
2009 ad hoc group to create two sets of criteria. The first set concerns the essential
characteristics of vaccine(s) that could be used immediately in a stockpile for emergency
response. The second group outlines the desirable characteristics of cholera stockpile
vaccine(s) of the future. With the first set, it was acknowledged that there was some difficulty
 10

in developing a priori criteria, since two prequalified vaccines exist and their characteristics
and relative strengths and weaknesses are well known in the cholera vaccine community.
Nevertheless, participants followed the Chair’s instruction that they should be guided not by
what is known to be available but by what is assessed to be essential.

In addressing formulation of the advice, the Working Group reviewed evidence on and
discussed the various issues including the following.

• Is the vaccine safe and effective in pregnant women?

• Does the vaccine protect against both Inaba and Ogawa serotypes?
• Does the vaccine need to be given with a buffer?
• Can the vaccine be administered without water or liquid other than the formulated
vaccine?
• Does the vaccine require a cold chain in the field?
• Can a single dose confer protection?
• How soon after immunization is protection evident?
• What is the shelf-life of the vaccine?
• What is the vaccine’s final shipping package weight and volume?
• Could health workers who administer oral polio vaccine also give the OCV?
• How is the vaccine packaged and presented, e.g. in single or multiple doses?

The Working Group concurred on the points summarized in Table 1. These criteria for
vaccine(s) for use in an immediate stockpile mainly mirror those provided by the 2009 ad hoc
group; differences are listed in the footnotes. The criteria for a stockpile vaccine for the
medium term reflect key areas for future OCV research and development that would simplify
and facilitate administration in the field.

Key point 4.1: The Working Group agreed on a matrix of criteria to guide the
choice of vaccine(s) to be stockpiled. OCV characteristics that should guide the
development of new vaccine were also outlined.
 11

Table 1: Criteria for candidate stockpile oral cholera vaccines

Candidate oral cholera vaccine requirements

For immediate For medium-term stockpile

a
stockpile

Confers protection against O1 El Tor (Inaba and O1 El Tor (Inaba and Ogawa)
Ogawa)

Number of doses required for 2 doses 1 dose

protection

Indication ages ≥2 years All age groups

Safety/tolerability profile Only mild, short-term Only mild, short-term side-

side-effects acceptable effects acceptable

Immunocompromised status No known risk of Safe and immunogenic for

(including HIV infection) whole-cell killed administration
contraindicated? vaccines in pregnant
women and
immunocompromised
individualsb

Time of onset of protection after 2–4 weeks < 2 weeks

full vaccination

Efficacy 6 monthsc after ≥50% ≥50%

vaccination

Minimum duration of sustained 1 year 1 year

protection

a
Criteria are the same as those listed for cholera vaccines proposed by the ad hoc Cholera Vaccine Working
Group of the Strategic Advisory group of Experts (SAGE) on Immunization, unless listed in these footnotes.
b
See Cholera Vaccines: WHO position paper. Weekly Epidemiological Record. 2010;85:117–128.
c
ad hoc Cholera Vaccine Working Group noted: 2 years.
 12

Candidate oral cholera vaccine requirements

For immediate For medium-term stockpile

a
stockpile

Ability to confer herd Desirable but not Desirable but not necessary
protection? necessary

Formulation Single formulation for Single formulation for all

all ages, including very ages, including very young
young children children

Buffer acceptable? Yes Yes

Can be administered with local Yes Yes

water (with or without
chlorination)?

Presentation and packaging Multi-vial packaging of Multi-vial packaging of

single-dose vialsd single-dose vials or multi-
dose vials

Cold chain requirements 2–8°C Heat stable

Minimum shelf life 2 years ≥3 years

Country registration Preferable but not Preferable but not necessary

necessary (authorization (authorization to use still
to use still needed) needed)

WHO prequalification Necessarye Necessary

d
ad hoc Cholera Vaccine Working Group noted: Multi-dose or single-dose packaging.
e
ad hoc Cholera Vaccine Working Group noted: Not if a specific country wants to use and is willing to pay for
the vaccine (prequalification required for donor funding and UN procurement).
 13

5. Epidemiological criteria for OCV stockpile use

In some cholera-endemic countries, targeted cholera vaccination is being considered as an
addition to the classical prevention and control measures of surveillance, case management,
and improving water, sanitation, and hygiene. The Working Group acknowledged that as
such activities progress, more evidence to help inform the use of vaccination as a
complementary cholera epidemic prevention and control measure will accrue.

The Working Group reviewed the complexity in forecasting the severity of cholera epidemics
and the likely impacts of interventions. Cholera presents particular challenges to quantitative
modelling, which include lack of understanding of the vibrio biology, the respective roles of
person-to-person and environmental transmission, and the particular spatial heterogeneity of
cholera that makes it difficult to generalize insights from one location to another.

While acknowledging the difficulty in predicting cholera epidemics and forecasting the likely
impact of vaccination, the Working Group agreed that, pending more detailed empirical data,
the following points might be considered when assessing the projected severity of a newly
detected cholera outbreak.

• Severity is, in this context, defined by the anticipated morbidity, mortality and the
likelihood of spread of cholera from an affected area to a non-affected area.
• The impact of vaccination would depend on:
o Susceptibility of the population, i.e. the level of herd immunity that may have
been conferred by earlier exposure to cholera (i.e. from previous outbreaks or
from endemic situations) or by vaccination in a particular population.
o Vulnerability of the population, i.e. behavioural, social, and environmental
factors likely to impact on the risk of acquiring infection and engaging in risk
minimization (e.g. mobility; health-seeking behaviours and access to health
care; hygienic practices; and access to safer food, water, and sanitation).
o Risk of spatial extension, i.e. the projected likelihood of geographic spread
when susceptibility and vulnerability are taken into account.
• A cholera outbreak is defined at the level of a district, a town, a neighbourhood, or a
refugee or transient community settlement. Nationwide outbreaks consist of the
succession and addition of several epidemic waves evolving over time and place.
• Any given area, e.g. district, town, neighbourhood, or refugee/internally displaced
persons site, is considered endemic for cholera if cases or deaths have been reported
 14

and laboratory confirmed during 3 of the previous 5 years. Otherwise, it is considered

non endemic.
• Stockpile vaccine will be deployed only after the reporting of a culture-confirmed
cholera outbreak (with consideration for the number of specimens collected, type of
strain, and laboratory capacity) in any given area, if the impact of the vaccination
campaign is estimated to be potentially high.
• Stockpile vaccine will not be deployed if an OCV campaign has been conducted in
the previous 2 years in the same area (with consideration for the quality of the
campaign, the vaccine coverage, and any population movements).

Once an outbreak of cholera has been laboratory confirmed in a given area, a number of
indicators may be considered to estimate the potential impact of the vaccination campaign,
based on the susceptibility of the population, the overall vulnerability of the population
exposed, and the risk of spatial extension as defined above (Table 2). Since an OCV strategy
is likely to cover a broader geographical area than the district, town, or neighbourhood
originally affected, the indicators should be applied not only to the affected community but
also to surrounding areas where the outbreak could potentially spread. Ethical issues involved
in the fair distribution of vaccines should be considered in parallel with epidemiological
criteria.

Key point 5.1: The Working Group agreed a set of epidemiological criteria that
should inform a decision to release stockpile vaccine in response to an outbreak.
 15

Table 2: Epidemiological and demographic considerations for OCV

stockpile deployment

Criterion Indicator Decision Potential impact

threshold of vaccination
campaign

High Low

Susceptibility of Number of cases reported in No or few cases X

the population the affected area(s) during the reported
past 2–3 years
High number of X
cases reported

Attack rate of previous High attack rate X

outbreaks in the affected
Low attack rate X
area(s)a

Vulnerability of Case-fatality rate (CFR) of High CFR X

the population previous outbreaks in the
Low CFR X
affected area(s)b

Refugee camp, internally Yes X

displaced people, or slums
No X
present in the affected area(s)

Area(s) with important Yes X

population movements (border,
No X
market hub, etc)

Population density in affected High density X

area(s)
Low density X

Access to water, sanitation, Poor access X

hygiene, and health care?
Good access X
 16

Risk of spatial Time elapsed / maturity of the Few weeks X

extension outbreak since first case
Few months X
reportedc

Attack rate since the start of the Low attack rate X

current outbreak (i.e.
High attack rate X
cumulative cases)a

Proportion of health units in the Low proportion X

district reporting casesd
High proportion X

Time at which first cases were First cases notified X

notified during the epidemic early in the season
e
season
First cases notified X
late in the season

a
The calculation of attack rates will rely on the availability of population figures. In some instances, cholera
attack rates are overestimated because all cases of acute watery diarrhoea are included in the numerator. In
general, the quality of the data should be checked when using this indicator. According to Médecins Sans
Frontières (MSF) guidelines,10 the maximum expected attack rate (i.e. the “worst case scenario”) would be 5%
of the entire population in refugee settings and urban slums, and 2% in rural areas. These figures might however
be exceeded in completely naive population as occurred in 2010 in Haiti.
b
The CFR is likely to be underestimated if all cases of acute watery diarrhoea (and not only cases of cholera)
are included in the denominator. Only deaths occurring in health-care facilities are usually reported. In general,
the quality of the data should be checked when applying this indicator. According to WHO, CFR should remain
below 1% with proper treatment.11
c
The duration of cholera outbreaks within a given area present a high degree of variability. Examples include
Mozambique: range 1–25 weeks, mean 7.2 weeks;12 and Uganda: range 4–27 weeks.13
d
The localisation of the health units is used as a proxy indicator for the localisation of the cases to estimate the
current extension of the outbreak, since the exact addresses of cases would most likely be unavailable at national
level. Countries applying for stockpile vaccines should actively seek reliable information about cases of acute
watery diarrhoea from all health units in the affected district(s).
e
In some areas, cholera outbreaks occur on a regular basis, every year or so, usually during the rainy season.
 17

The Working Group emphasized that the indicators presented in Table 2 should be used only
as advice to inform decision-making and should be considered together with a thorough
awareness of the operational capacity of the country to complete a mass vaccination
campaign. None should be considered sufficient to make a final decision. Deployment of
vaccines from the OCV stockpile should follow analysis of not only the indicators presented
in the table but also assessment of programmatic factors such as the local capacity to organize
a campaign and the prevailing security conditions.

The WHO Strategic Advisory Group of Experts on Immunization (SAGE) has created a
Working Group to develop a framework for public health decision-making for vaccination in
humanitarian emergencies.14 The SAGE Working Group is developing a similar matrix of
issues to consider when assessing the need for an emergency vaccine response, which
includes implementation capacities, local context factors, and ethical aspects. This matrix was
used by the Working Group to frame their discussions. Participants noted the alliance
between their work and that of the SAGE Working Group and recognized the merits of
sustained, close collaboration in the future.

The Working Group noted that the primary purpose of the stockpile is for outbreak response.
However, there may be instances when OCV supply (from the market or other sources) for
vaccination in humanitarian emergency settings is not readily available. The Working Group
agreed that, in such situations, OCV could be considered for release from the stockpile to
enable prompt and timely action, and should then be replenished as soon as possible using
emergency response funds.

Key point 5.2: The Working Group agreed that requests for use of OCV from
the stockpile in humanitarian emergencies could be considered if vaccine supply
from standard sources is not readily available. Emergency response funds
should be used to replenish the vaccine used from the stockpile.

6. Global governance of the OCV stockpile

Participants discussed the background to the creation of the two existing stockpiles for
meningococcal and yellow fever vaccines, and whether they would serve as a viable model
for the OCV stockpile. In 1996, Africa experienced the largest recorded outbreak of epidemic
meningitis in history, with more than 200 000 cases and 20 000 deaths. The emergency
response fully exhausted international vaccine reserves. In 1997, an International
 18

Coordinating Group (ICG) to oversee a vaccine stockpile was created with an initial
US$1 million donation from WHO. The aim was “to assure a well-coordinated and equitable
distribution of meningococcal vaccines and related material during meningitis epidemics”.
The yellow fever vaccine stockpile was created in 2001 in response to an outbreak in Côte
d’Ivoire, with an initial stock of 2 million doses.

The ICG decision-making body is composed of representatives from Médecins sans

Frontières (MSF), the International Federation of the Red Cross and Red Crescent Societies
(IFRC), UNICEF, and WHO. Additional expertise and technical advice might be sought on a
case-by-case base from a range of partners including the Agence de Médecine Preventive in
Paris, Epicentre in Paris, and WHO Collaborating Centres. Vaccine manufacturers, vaccine
equipment providers, and financial donor institutions are also engaged in ICG operations. A
meeting with participation of key stakeholders is organized annually.

The overarching goal of the ICG is to ensure timely and targeted deployment such that
vaccine can be used as an effective outbreak response where it is most needed. The ICG
manages the global stock and liaison with manufacturers ensures that emergency supplies are
available at the global level. The ICG decision-making body uses, and promotes the need for,
epidemiological and operational criteria for vaccine release. Standard operating procedures
are followed, which are transparent and allow lessons to be learned and activities to be
improved.

Since the inception of the ICG, much progress has been made on refining the procurement
and deployment of vaccines for meningitis and yellow fever. Work has been done at the
country level to improve the quality of requests to the ICG, guidelines and forms have been
revised and improved, and direct support has been given to countries, including evaluations
of epidemic detection and response. The ICG mechanism has also contributed to
improvements in surveillance and laboratory confirmation as countries must demonstrate an
ongoing epidemic in order to access the ICG stockpile.

On average, 10–35 vaccine requests are received and assessed within a 3-month meningitis
epidemic season. The day-to-day running and executive coordination is done by the ICG
decision-making group, which makes a decision on each request within 48 hours. Vaccine is
delivered to the requesting country within seven days of a positive response. More than 50
million doses of meningococcal vaccines have been deployed via the stockpile since 1997, all
for outbreak response. Ninety million doses of yellow fever vaccines have been released for
both outbreak and preventive use since 2001.
 19

Initial funding shortfalls limited the ICG’s ability to respond to outbreaks but GAVI
financing for both stockpiles is now secured until 2013. A revolving fund mechanism was
established in 2010 for both stockpiles – in which donors or countries will reimburse the fund
for vaccines used – in order to sustain the stockpiles once GAVI funding ends. Since this
mechanism was put in place, US$ 4 million has been reimbursed, with 94% fund recovery in
2011.

The Working Group members agreed that there was a clear rationale for employing a similar
structure for oversight the OCV stockpile. Representatives of the four members of the ICG
decision-making group indicated their organizations’ readiness, in principle, to extend their
mandate to the governance of the OCV stockpile.

The Working Group agreed that this decision-making group would be charged with
developing its own terms of reference. Participants underscored the need to be aware of the
sensitivity about cholera reporting and for discretion regarding stockpile request procedures,
such as to encourage countries to meet their reporting requirements under the International
Health Regulations (2005).15

The Working Group acknowledged that other international bodies might wish to join the
OCV ICG decision-making group. Participants therefore agreed that any members beyond
MSF, IFRC, UNICEF, and WHO must fulfil the criteria below. Applications should be made
via the ICG Secretariat at WHO and applicants must:

• Be an international agency or organization.

• Have no conflict of interest, i.e. must not be involved in cholera vaccine manufacture,
perform consultancies for and/or receive funding from such manufacturers, be
involved in research for development of cholera vaccines, or expect profits of any
kind from membership.
• Demonstrate involvement in cholera prevention and control interventions.
• Be committed to be available for emergency consultation at any time, at least through
electronic means.
• Undertake to act with discretion with respect to data received for decision-making
purposes, given the sensitivities of cholera data to national interests.

The Working Group agreed that the decision-making body should be supported by a wider,
consultative, assembly of partners allied with cholera prevention and control. A key objective
of this ICG partnership should be to stimulate coordination of international efforts in
 20

preparing for and responding to epidemics, especially through enhanced synergy between the
use of OCV and other cholera control measures. The Working Group emphasized that such
collaboration and synchronization is essential, since there are many different organizations
and projects within the global cholera-response community, thus a risk of duplication of
efforts exists.

In addition, the partnership should contribute to rapid access to vaccines by countries

experiencing cholera epidemics and promote optimal use of cholera vaccines during
epidemics, especially when stocks are limited.

Key point 6.1: The International Coordinating Group (ICG) decision-making

body comprising MSF, IFRC, UNICEF, and WHO that oversees the
meningococcal and yellow fever vaccine stockpiles should extend its mandate to
include OCV. This body is charged with developing its own terms of reference
and will require funding to cover the added operational costs. Criteria for any
additional members were defined. The OCV ICG should be nested within a
wider group of organizations (e.g. technical, commercial, civil society, funding)
that can inform the partnership on their specific areas of expertise.

Given the work done by the existing ICG in recent years to refine the mechanism for
application and decision-making, the Working Group agreed that the OCV ICG should mirror
this procedure. Thus, a request for stockpile vaccine deployment may be submitted by any
national or international organization, such as a Ministry of Health or nongovernmental
organization. A decision must be made on any such request within 48 hours (2 working
days). Decisions should be made by use of pre-established epidemiological criteria. Each of
the four organizations in the decision-making group has one vote. Decisions should be
reached by consensus, usually by e-mail. If there is disagreement, a teleconference should be
convened immediately so that consensus might be reached. If disagreement persists, the
decision should be made by majority. The decision types available should be: (1) approval;
(2) partial approval (e.g. where less vaccine than requested is approved); (3) more
information needed; or (4) rejection.

Key point 6.2: The Working Group agreed that submission of a vaccine request
may be made by any national or international organization. On receipt of such a
request, the ICG should make a decision within 48 hours.
 21

Key point 6.3: The OCV stockpile vaccine should be targeted at epidemics in
those countries where cholera is going to cause a significant burden.
Participants agreed that the OCV stockpile vaccine should be targeted at
epidemics in low-income countries.

7. Working mechanism of the OCV stockpile

The Working Group referred to various aspects of the mechanism of the ICG for the
meningitis and yellow fever stockpiles, stock management, storage, applications
procurement, shipping, and financing. Members felt that the most pragmatic approach was to
examine the current ICG’s working mechanism and replicate this process for the OCV
stockpile, with modifications relevant to a cholera outbreak response where appropriate.

Decisions on the size of the stockpile were informed by realistic forecasts of what might be
achievable in the short term with either or both of the candidate prequalified vaccines. An
initial stockpile of two million doses per year was advised by the Working Group. This size
might, and indeed should, change as the stockpile and vaccine development and production
capacities evolve and financing grows.

Key point 7.1: The Working Group agreed that the OCV stockpile should
initially comprise two million doses per year.

Participants agreed that a 5-year projected stockpile timeframe would be sufficient in the first
instance, with a mid-term evaluation. Stock management should mirror experience with the
meningococcal and yellow fever vaccine stockpiles, whereby stocks are held by the
manufacturers. This arrangement facilitates rapid delivery via established air connections,
optimizes the vaccine shelf-life, and simplifies the overall management of the stockpile
logistics.

The Working Group agreed that, as with the existing stockpiles, country receipt of OCV
should be within 7 days of approval of a request. Whether this target should apply to all the
vaccine required (i.e. 2 doses for each individual targeted) or to only the first dose of a
regimen, the Working Group noted that this goal would depend on the vaccine/manufacturer
selected, as well as such variables as geographical remoteness of the target population and
need to be flexible and opportunistic with availability of flights, likelihood of the acceptance
of vaccines by the target communities, capacity of the national cold-chain, and other logistic
factors.
 22

A key concern was how to ensure that deployed OCV will be used appropriately, given that
anticipated stock will be low and demand high. While the Working Group agreed that no
binding advice could or should be made at this stage, it emphasized that monitoring and
evaluating the efficiency and effectiveness of the stockpile should inform development of
such procedures as the scheme is rolled-out.

With regard to financing, the Working Group agreed that the most prudent option would be to
seek initial donor funding to finance the first 2–3 years of the stockpile. Such funding would
be used to finance procurement of two million OCV doses per year and operating costs to
strengthen surveillance and preparedness to mount epidemic vaccination campaigns at the
country level. As with the existing meningococcal and yellow fever vaccine stockpiles, a
revolving fund mechanism should be established such that financial stability is maintained
once initial donor funding has expired.

Key point 7.2: The Working Group agreed the storage of stockpile vaccine
should be the responsibility of the manufacturer. The stockpile should be
maintained on a rotating stock basis.

Key point 7.3: Initial donor contributions should be sought to fund vaccine
procurement, country preparedness, and planned operational costs for the first
2-3 years based on the extensive experience of the ICG. A revolving fund should
be established to assure longer-term financial stability.

8. Procurement of OCV for a stockpile

UNICEF Supply Division (UNICEF/SD) acts as the procurement agency for the existing ICG
for meningococcal and yellow fever vaccines. The Working Group agreed that, although
other procurement organizations exist, it would be prudent for UNICEF/SD to act in this
capacity for the OCV stockpile. UNICEF/SD’s procurement strategies are focused on
achieving vaccine security – the sustained, uninterrupted supply of affordable, quality
vaccines – while acknowledging the different forces in individual markets. UNICEF abides
by seven procurement principles, which were invoked following the supply crisis in the
traditional vaccine markets:

• There should be procurement from multiple suppliers for each vaccine presentation.
• Procurement should be from manufacturers in both developing and industrialized
countries.
 23

• The price paid should be affordable to governments and donors and should reasonably
cover manufacturers’ minimum requirements.
• UNICEF should provide manufacturers with accurate and long-term forecasts;
manufacturers should provide UNICEF with accurate and long-term production plans.
• Since UNICEF is a public buyer, provision of grants is not the most effective method
of increasing capacity.
• Manufacturers should have the option of quoting tiered pricing.
• A healthy vaccine industry is vital to ensuring uninterrupted and sustainable supply.

The Working Group agreed that UNICEF/SD should establish a Procurement Reference
Group to advise on technical issues regarding OCV and stockpile specifications and to
evaluate tender applications. The membership, terms of reference, and decision-making
process for this group should be defined jointly by UNICEF and WHO.

Participants agreed that the initial tender issued by UNICEF/SD should be for the
establishment of a 3-year supply of vaccine. Should that arrangement not be possible within
the OCV market, the initial supply could be set at 1 year, with an option of extension to 3
years. The Working Group agreed that a tender for a 5-year supply agreement would not be
advisable.

Members of the Working Group agreed that a reserved rather than pre-paid stockpile would
be preferable. A reserved stockpile would have the advantages that there would be no risk of
unused purchased vaccine and availability of supply would be assured. As with the
meningococcal and yellow fever vaccine stockpiles, once the ICG has approved the release of
vaccine, UNICEF/SD would issue a procurement order to instruct the manufacturer(s) to ship
the vaccine to the country where the outbreak is located. Payment of the vaccine is made 30
days after the issuance of the procurement order.

Key point 8.1: The Working Group agreed that a Procurement Reference Group
should be established by UNICEF/SD to advise on technical issues regarding
vaccine and stockpile specifications. A reserved rather than prepaid stockpile is
preferred.
 24

9. Evaluation and external review of OCV stockpile

The Working Group agreed that clear mechanisms should be put in place for 1) evaluation of
outbreak response and 2) monitoring and evaluation of the functioning of the ICG. As a first
principle, the OCV ICG should mirror the oversight of the meningococcal and yellow fever
stockpiles, with annual meetings of all the extended ICG partners. In addition, the group
underscored that a rigorous system of short- and longer-term monitoring and evaluation
should be embedded within the OCV stockpile mechanism. The Working Group noted that
successful assessment of a stockpile vaccination campaign would require reinforcement of
surveillance systems in most locations where an epidemic is likely to arise.

Participants agreed that WHO should establish a stockpile evaluation group to define and
implement the detailed monitoring required. As experience and data accrue, the results of this
evaluation should enable continuous improvement in the structure and functioning of the
stockpile. The evaluation group should report to all relevant stakeholders, including stockpile
decision-makers, past and potential requesting countries or organizations, donors, and
technical partners. While the evaluation group will define the data to be collected and
assessed, the Working Group suggested the following baseline activities, evaluations, and
indicators.

• The timeliness and transparency of the ICG decision-making body’s approval process
should be monitored.
• Where approval is granted, wholly or partially, the timeliness of deployment should
be evaluated.
• Evaluation of an OCV stockpile deployment should be done by the collection and
assessment of data that include:

o Number of cases of cholera (clinical and laboratory confirmed) in the vaccinated

area
o Population acceptability of the vaccination campaign
o Vaccine coverage per round and per age group
o Drop-out rate between the first and second round (and third, if applicable) and off-
target vaccinated populations
o Vaccine effectiveness in population receiving 1 dose and in those receiving 2
doses (and 3 doses, if applicable); such studies will take some time to complete
o Overall duration and cost of campaign: actual versus projected
o Material resources required
 25

o Human resources required, including training and supervision

o Logistics and infrastructure issues: transport, impact of the OCV campaign on
Expanded Programme of Immunization and cold-chain infrastructure
o Vaccine wastage

• Where the vaccine request is refused, the impact of this decision should be evaluated.
Suggested indicators to monitor include the duration of the outbreak and weekly
number of cases, plus the availability, functioning, and impact of treatment and non-
vaccine prevention measures within the outbreak area as well as ability of the local
authority to procure vaccine from alternative sources.
• In the longer term, an evaluation of the worldwide effect of the existence of the OCV
stockpile will be required. Assessments should be made of the efficiency and impact
of the stockpile and its effects on total OCV demand and use, manufacturing capacity,
and global cholera trends.
• More detailed analysis of the utility of the stockpile should be done in selected areas
to assess: vaccine effectiveness; local disease trends; impact on water, sanitation, and
hygiene activities; cost-effectiveness; and acceptability.

Key point 9.1: The Working Group agreed that a rigorous system of short- and
longer-term monitoring and evaluation should be embedded within the OCV
stockpile mechanism. WHO should establish a stockpile evaluation group to
define and implement the detailed monitoring required. As experience and data
accrue, the results of this evaluation should enable continuous improvement in
the structure and functioning of the stockpile.

10. Next steps and timeline

The Working Group agreed next steps and a timeline for action during 2012. These are
summarized below. WHO will:

• Recruit ICG focal points for cholera stockpile from partner institutions and agree
terms of reference agreed (July).
• Advocate for and seek financial support and prepare and submit proposals to: the
European Union, the Bill & Melinda Gates Foundation, GAVI, the United Kingdom
 26

Department for International Development, and the United States Agency for
International Development (ongoing).
• Inform WHO Headquarters, Regional Offices, Member States, and partners about the
planned availability of OCV stockpile and disseminate of epidemiological and
operational criteria (October).
• Convene OCV stockpile working group to define a template for deployment
evaluation (October).
• Liaise with SAGE Vaccination in Emergencies Working Group to ensure that the
consensus of this meeting is compatible with the development of the SAGE
Framework (June).
• Meet vaccine producers to discuss production capacity, vaccine presentation, storage
capacity, etc (September).
WHO and UNICEF/SD will:
• Develop a procurement strategy that includes milestones for different tender processes
(October).
• Convene a Procurement Reference Group to evaluate the bids. This will only be
possible once finance is in place.
 27

11. References
1. 64th World Health Assembly. Cholera: mechanism for control and prevention resolution,
24 May 2011. WHA 64.15. 2011. Available from:
http://www.who.int/cholera/technical/resolution/en/index.html, accessed 21 May 2012.

2. WHO Consultation on oral cholera vaccine (OCV) stockpile strategic framework: potential
objectives and possible policy options. 18-20 September 2011, Geneva, Switzerland . 2012.
Available from: http://whqlibdoc.who.int/hq/2012/WHO_IVB_12.05_eng.pdf, accessed 5
May 2012.

3. Clemens JD, Sack DA, Harris JR, Chakraborty J, Khan MR, Stanton BF et al. Field trial of
oral cholera vaccines in Bangladesh. Lancet. 1986;2(8499):124–27.

4. Ali M, Emch M, von Seidlein L, Yunus M, Sack DA, Rao M et al. Herd immunity
conferred by killed oral cholera vaccines in Bangladesh: a reanalysis. Lancet.
2005;366(9479):44–49.

5. Sanchez JL, Vasquez B, Begue RE, Meza R, Castellares G, Cabezas C et al. Protective
efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military
recruits. Lancet. 1994;344(8932):1273–76.

6. Lucas MES, Deen JL, von Seidlein L, Wang XY, Ampuero J, Puri M et al. Effectiveness
of mass oral cholera vaccination in Beira, Mozambique. N Engl J Med. 2005;352(8):757–67.

7. Sur D, Lopez AL, Kanungo S, Paisley A, Manna B, Ali M et al. Efficacy and safety of a
modified killed-whole-cell oral cholera vaccine in India: an interim analysis of a cluster-
randomised, double-blind, placebo-controlled trial. Lancet. 2009;374(9702):1694–702.

8. Sur D, Kanungo S, Sah B, Manna B, Ali M, Paisley AM et al. Efficacy of a low-cost,

inactivated whole-cell oral cholera vaccine: results from 3 years of follow-up of a
randomized, controlled trial. PLoS Neglected Tropical Diseases. 2011;5(10):e1289.

9. ad hoc Strategic Advisory group of Experts (SAGE) Cholera Vaccine Working Group.
Background paper on the integration of oral cholera vaccines into global cholera control
programmes. 2009. Available from:
http://www.who.int/immunization/sage/1_Background_Paper_Cholera_Vaccines_FINALdraf
t_13_oct_v2.pdf, accessed 21 May 2012.

10. Cholera guidelines, second edition. 2004. Available from:

http://www.bvsde.paho.org/texcom/cd045364/choleraguide.pdf, accessed 22 May 2012.

11. Cholera. Fact sheet no. 107. 2011. Available from:

http://www.who.int/mediacentre/factsheets/fs107/en/index.html, accessed 21 May 2012.

12. Oral presentation at Annual Regional Conference on Immunization (ARCI). Windhoek,

Namibia, 8–12 December 2011.

13. An investment case for the accelerated introduction of oral cholera vaccines. 2012.
Available from: http://www.ivi.int/publication/IVI_Global_cholera_case.pdf, accessed 21
May 2012.
 28

14. SAGE Working Group on Vaccination in Humanitarian Emergencies. Available from:

http://www.who.int/immunization/sage/sage_wg_hum_emergencies_jun11/en/index.html,
accessed 5 May 2012.

15. International Health Regulations (2005). 2008. Available from:

http://whqlibdoc.who.int/publications/2008/9789241580410_eng.pdf, accessed 21 May 2012.
 29

12. Annex I: List of participants

Technical Working Group: Oral Cholera Vaccine Stockpile

26–27 April 2012

Ms Ana Balmes
Contracts Manager
Vaccine Center
UNICEF Supply Division
Copenhagen, Denmark

Dr Francesco Checchi
Faculty of Infectious and Tropical Diseases
London School of Hygiene and Tropical Medicine
United Kingdom

Dr John Clemens #
Professor of Epidemiology
Department of Epidemiology
UCLA School of Public Health
Center for Health Sciences
Los Angeles, USA

Dr Alejandro Cravioto
Executive Director
International Centre for Diarrhoeal Disease Research (ICDDR'B)
Dhaka, Bangladesh

Dr Yonatan Grad
Center for Communicable Disease Dynamics
Harvard School of Public Health
Harvard University
Boston, USA

Dr Rebecca Grais
Epidemiologist
Epicentre MSF
Paris, France

Dr Myriam Henkens
Médecins Sans Frontières
International Office
Brussels, Belgium

Dr Dominique Legros
Independent Consultant
Switzerland
 30

Dr Myron M. Levine #
Grollman Distinguished Professor and Director
University of Maryland School of Medicine
Center for Vaccine Development
Baltimore, USA

Mr Ian Lewis
Contracts Specialist
Vaccine Centre
UNICEF Supply Division
Copenhagen, Denmark

Dr Francisco Luquero
Epidemiologist
Epicentre MSF
Paris, France

Dr Rebecca Martin*
Director, Global Immunization Division
Center for Global Health
Centers for Disease Control and prevention
Atlanta, USA

Dr Martin Mengle
Project Coordinator - Africhol
African Cholera Surveillance Network
Agence de Médecine Préventive
s/c Institut Pasteur
Paris, France

Dr Eric Mintz
Team Lead, Global WASH Epidemiology
Division of Foodborne, Waterborne, and Environmental Disease
Centers for Disease Control and Prevention (CDC)
Atlanta, USA

Dr Heather Papowitz
Senior Advisor Health-Emergencies
UNICEF - Health Section
New York, USA

Dr Sarah Ramsay
Independent Consultant
United Kingdom

Dr Panu Saaristo
Senior Officer, Emergency Health Coordinator
Water, Sanitation and Emergency Health Unit
Health Department
International Federation of Red Cross and Red Crescent Societies
Geneva, Switzerland
 31

Prof Daniel Tarantola (Chairperson)

Visiting Professorial Fellow
School of Public Health and Community Medicine
Faculty of Medicine
The University of New South Wales
Sydney, Australia

Dr Tom Wierzba #
International Vaccine Institute
Seoul, The Republic of Korea

Dr Catherine Yen
Medical Epidemiologist
Global Immunization Division
Strengthening Immunization Systems Branch
Centers for Disease Control and Prevention (CDC)
Atlanta, USA

WORLD HEALTH ORGANIZATION

REGIONAL OFFICES

Dr Benido Impouma AFRO

Dr Andrea Vicari AMRO/PAHO
Dr Hassan El M. Bushra EMRO
Dr Brent Burkholder SEARO

HEADQUARTERS

Mr Jean-Christophe Azé HSE/GCR

Dr Claire-Lise Chaignat HSE/PED/CED
Mr Alejandro Costa HSE/PED/CED
Mr Patrick A. Drury HSE/GCR
Dr Philippe Duclos FWC/IVB
Ms Katya Fernandez HSE/PED/CED
Dr Keiji Fukuda HSE/PED
Mrs Alexandra Hill HSE/PED/CED
Dr Raymond Hutubessy FWC/IVR/IMR
Dr Stephen Martin HSE/PED/CED
Dr Pem Namgyal FWC/IVR/IMR
Dr William Perea HSE/PED/CED
 32

# The following participants, for reasons of interest in the subject matter of the meeting,
agreed to absent themselves from the sessions at which the meeting recommendations were
developed. Their participation was thus strictly limited to the sessions dealing with the
general exchange of information and views.

Dr J. Clemens: The research unit at the International Vaccine Institute, Seoul, Korea (of
which Dr Clemens was Director from 1999 to 2010) developed to licensure the oral cholera
vaccine ShancholTM. As part of this development, his unit received a significant in-kind
donation of vaccine for the conduct of vaccine trials.

Dr M. M. Levine: Dr Levine has provided advice to and received reimbursement of travel

expenses from companies with an interest in oral cholera vaccine. In addition, Dr Levine is
co-inventor of an oral cholera vaccine candidate which is being developed in collaboration
with a vaccine manufacturer.

Dr Tom Wierzba: Dr Wierzba is a member of the Executive Leadership Team of the

International Vaccine Institute, Seoul, Korea which has been closely involved with the
development of an oral cholera vaccine.
 33

13. Annex II: Meeting agenda

Chair: Professor Daniel Tarantola

Day One: Thursday, 26 April 2012

Objectives
1. Reach consensus on criteria for inclusion of cholera vaccines in stockpile
2. Reach consensus on epidemiological criteria, indicators for predictability of o/b severity:
3. Agree on principles of stockpile intervention evaluation

TIME DURATION SESSION TITLE FACILITATOR

(minutes)
8:30 - 8:45 15 Participant registration

8:45 - 9:00 15 Introduction, opening remarks Keiji Fukuda

Overview of scope of meeting, expected results Daniel Tarantola

9:00 - 9:20 20 Overview WHO prequalified cholera vaccines Mike Levine

9:20 – 9:30 10 Overview of OCV criteria for stockpile inclusion Dominique Legros

9:30 - 10:00 30 Discussion : vaccine criteria for inclusion in

stockpile

10:00 - 10:15 15 Summary: suggestions stockpile vaccine criteria

10:15 – 10:30 15 COFFEE BREAK

10:30 – 10:50 20 Epidemiological criteria for use of OCV R. Freeman-Grais

stockpile

10:50 – 11:10 20 Cholera modelling: Challenges of quantitative Yonatan Grad

analysis and prediction of the impact of
interventions

11:10 – 11:30 20 Epidemiological definitions, suggested criteria Dominique Legros

11:30 – 12:30 80 Discussion

12:30 – 13:30 60 LUNCH

13:30 – 15:15 120 Continued discussion epidemiological criteria

15:15 – 15:30 15 Summary: suggested epidemiological criteria

15:30 – 15:45 15 COFFEE BREAK

15:45 – 16:30 45 Evaluation/external review of OCV stockpile in Catherine Yen

epidemic response and validation of criteria

16:30 – 18:00 90 Closed session: Recommendations on vaccine,

epidemiological criteria + evaluation
 34

Day Two: Friday, 27 April 2012

Objectives:
1. Agree on stockpile mechanisms (partnerships, decision making, financial, size, storage,
rotation, shipment and procurement)
2. Agree on next steps for implementation

TIME DURATION SESSION TITLE FACILITATOR

(minutes)

8:45 – 9:00 15 Debrief of Day 1, overview of Day 2 Daniel Tarantola

9:00 – 9:30 30 Partnership. Alejandro Costa

Katya Fernandez
Review mechanisms for Meningitis, Yellow
Fever, ICG Decision making process Financing
mechanisms. GAVI + other donors. Revolving
fund. Donation versus reimbursement

9:30 – 10:30 30 Vaccine procurement, tendering process, Ana Balmes

timelines, prepaid versus reserved stock.
Ian Lewis
OCV stockpile: Size, timeframe, storage, stock
rotation, shipment time, logistics

10:30 – 10:45 15 COFFEE BREAK

10:45 – 11:15 30 Stockpile Discussion: suggested partnership

11:15 – 11:45 30 Stockpile discussion: suggested decision

making process and mechanisms for
deployment

11:45 – 12:15 30 Stockpile discussion: suggested financial

mechanisms

12:15 – 13:00 45 LUNCH

13:00 – 13:30 30 Stockpile discussion: suggested procurement

mechanisms

13:30 – 15:30 120 Closed session: recommendations and next

steps

15:30 TEA + MEETING CLOSES