Oral Cholera Vaccine stockpile for cholera emergency response

ICG 9/16/2013

1

Table of Contents 1. Background ...................................................................................................................................... 2

1.1. Global burden of cholera ......................................................................................................... 2

1.2. World Assembly resolution and WHO technical consultations ............................................... 2

2. Characteristics of currently prequalified OCV ................................................................................. 3

2.1. General information ................................................................................................................. 3

2.2. Key features and performance of WHO pre-qualified oral cholera vaccines .......................... 4

3. When to consider the use of OCV? WHO position paper ............................................................... 6

3.1. Vaccination and cholera control .............................................................................................. 6

3.2. Control of endemic cholera ..................................................................................................... 6

3.3. Control of cholera outbreaks ................................................................................................... 7

3.4. Surveillance .............................................................................................................................. 9

4. Previous experience on OCV in mass vaccination campaigns ....................................................... 10

5. Stockpile mechanism overview ..................................................................................................... 16

5.1. Objectives of OCV stockpile ................................................................................................... 16

5.2. Use of the stockpile ................................................................................................................ 17

5.3. Management and governance of the OCV stockpile for emergency response7 .................... 17

5.4. Application procedure to OCV in IGC stockpile ..................................................................... 18

5.5. Decision criteria for the release of OCV. ................................................................................ 20

5.6. Monitoring and evaluation of the OCV stockpile ................................................................... 23

6. References: .................................................................................................................................... 24

2

Background

Global burden of cholera

The real global burden of cholera is unknown. In cholera endemic countries, an estimated 1.4 billion

people are at risk of cholera each year1 and 2.8 million cholera cases (uncertainty range: 1.4–4.3) and 91

000 cholera deaths (uncertainty range 28,000 to 142,000) occur every year. Another 87 000 cases and

2500 deaths are expected in non-endemic countries annually.1

Slow progress in providing access to safe water and sanitation to underserved populations, limitations of

surveillance systems for early detection of cholera outbreaks, and lack of access to timely and appropriate

healthcare have contributed to this burden of disease.Other factors contributing to make cholera a public

health priority are the emergence in 1992 of new strains of V. cholerae more virulent and causing more

severe clinical manifestations2, the increased antimicrobial resistance, climate change and rapid and

unplanned urbanization.3Children under five bear the greatest burden of cholera and account for about

half of the estimated cholera deaths.4

Effective cholera prevention and treatment regimens are well established, yet cholera remains poorly

controlled in both outbreak and endemic contexts.

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.

World Assembly resolution and WHO technical consultations

Recognizing the importance of cholera as a continuing public health problem, the World Health

Assembly adopted Resolution 64.15 in May 2011.5 This resolution calls for implementation of an

integrated and comprehensive approach to cholera control, which may include 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.”

In September 2011, the World Health Organization (WHO) Secretariat organized a technical consultation

which recommended the creation of an OCV stockpile for outbreak control.6

In April 2012, the WHO convened a Technical Working Group (WG) to address the creation of an oral

cholera vaccine stockpile and to develop the implementation framework.

3

The WG agreed that the focus would be specifically to respond to outbreaks, as a means to complement

but not replace existing guidance on other critical cholera outbreak prevention and control measures.7

Characteristics of currently prequalified OCV

General information For the creation of an immediate stockpile, two OCVs are currently prequalified by WHO: Dukoral

® and

Shanchol™. There is no known comparison of the two vaccines up to now. Their key attributes are

briefly outlined below and summarized in table 1.

Overall, both WHO pre-qualified are oral killed whole-cell vaccines (WC) that provide sustained

protection of >50% for at least two years in endemic populations8-10

induce an immune response relatively

quickly (7-10 days after the 2nd

dose) and have a good safety profile.11

Shanchol™ has demonstrated

longer term protection in children less than six years of age, as compared to Dukoral,® and therefore does

not require booster dose after six months in this age group, as does Dukoral®.12

On the other hand,

Dukoral® has been shown to provide better short-term protection against cholera, particularly among

children 2-5 years old and also confers significant short-term protection against ETEC.

In terms of logistics and handling, both vaccines have a two-dose regimen between 1 and 6 weeks apart.

(3 doses for Dukoral in children aged 2–5 years) and require a cold chain.

4

Key features and performance of WHO pre-qualified oral cholera vaccines

Table 1.Characteristics of WHO pre-qualified oral cholera vaccines.

Characteristics Oral cholera vaccines

Trade name Dukoral® Shanchol™

Type of vaccine Killed whole cell vaccine V.cholerae

O1 serogroup + recombinant B

subunit of cholera toxin (WC/rBS)

Killed bivalent (O1 and O139

serogroups ) whole-cell vaccine

suspension. (BivWC)

Presentation (or

packaging)

3 ml single dose vials and 5.6 g of

effervescent granules of sodium

bicarbonate buffer in a sachet

1.5ml single dose vials (in 3 ml glass

vial with aluminium cap)

Age From 2 years of age From 1 year of age

Administration

course or (Dosing)

- Adults and children 6 years and

older: 2 doses given orally 1-6

weeks apart. - Booster dose after 2

years.

- Children 2-5 years:

3 doses given orally 1-6 weeks

apart. Booster dose after 6

months.

- Fasting required 1 hour before

and after vaccination.

- 2 doses given orally 2 weeks apart.

- A period of +3 days is accepted for

second dose.

- No official recommendation on

booster yet.

5

Buffer Dilution in 150ml of water (75ml

for children 2-5 years) mixed with

buffer

- No buffer needed

- Water may be offered following

ingestion of the vaccine, but is not

required.

Protection/efficacy Earliest onset of protection 7 days

after 2nd dose.

- Earliest onset of protection 7-10

days after 2nd dose.

- 67% protection for at least 2 years

in all ages

Adverse effects

/contraindications

-No major adverse effects

reported.

-Currently not recommended for

use in pregnancy (no specific

studies performed)

-Administration may be considered

after benefit- risk evaluation.

-Can be given to HIV-infected

persons.

- No major adverse effects reported.

- Currently not recommended in

pregnancy (limited data )

- Currently not recommended in

HIV/AIDS or other immuno-

compromised states (No clinical data)

- Administration may be considered

after benefit- risk evaluation.

Shelf life, storage

and cold chain

- 3 year shelf life at 2-8° C.

- Stable for 1 month at 37 ° C . 2

weeks at < 27 ° C

- Do not freeze

- No VVM.

- Packed volume per dose: 136cm3

(in 2-dose pack; also available in

single and 20-dose pack)

- 30 months shelf life at 2-8° C

- Do not freeze

- VVM of type 14.

- Stable for 14 days at 37oC

- Packed volume per dose in 35-dose

pack:16.8cm3 (140 mm x105 mm x40

mm)

Manufacturer Crucell, (Sweden) Shantha Biotechnics, (Hyderabad,

India) Sanofi Company

6

Current production

capacity (2012)

2 million doses per year 2 million doses per year

Countries licensed

(June 2013)

Licensed in 60 countries India, Nepal, Malaysia, Philippines,

Ivory Coast

Year first licensed 1991 2009

Date of WHO

prequalification

25 Oct 2001 29 Sep 2011

Estimated prices per

dose (2013)

~ $ 4.7-9.4 per dose $1.85

When to consider the use of OCV? WHO position paper 24

Vaccination and cholera control Cholera control should be a priority in areas where the disease is endemic.

Given the availability of 2 oral cholera vaccines and data on their efficacy, field effectiveness, feasibility

and acceptance in cholera-affected populations, immunization with these vaccines should be used in

conjunction with other prevention and control strategies in areas where the disease is endemic and should

be considered in areas at risk for outbreaks.

Vaccination should not disrupt the provision of other high-priority health interventions to control or

prevent cholera outbreaks. Vaccines provide a short-term effect that can be implemented to bring about an

immediate response while the longer term interventions of improving water and sanitation, which involve

large investments, are put into place.

Although all age groups are vulnerable to cholera, where resources are limited immunization should be

targeted at high-risk children aged ≥1 year (Shanchol™ or mORCVAX) or ≥2 years (Dukoral®). (For

vaccine schedules and administration, see recommendations made by the manufacturers).

Control of endemic cholera The following definition for endemic cholera has been suggested: “the occurrence of faecal culture-

confirmed cholera diarrhoea in a population in at least 3 of the past 5 years”.25

Even in endemic settings

there may be surges in cholera incidence for which intensive public health interventions are required.

While such surges might be termed endemic, in public health terms they are often treated as epidemic

cholera.

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In cholera-endemic countries, vaccinating the entire population is not warranted. Rather, vaccination

should be targeted at high-risk areas and population groups.

The primary targets for cholera vaccination in many endemic areas are preschool-aged and school-aged

children.

Other groups that are especially vulnerable to severe disease and for which the vaccines are not

contraindicated may also be targeted, such as pregnant women and HIV-infected individuals. Countries

should also consider vaccinating older age groups if funding is available.

Periodic mass vaccination campaigns are probably the most practical option for delivering cholera

vaccines.

Schools, health-care facilities, religious institutions and other community settings may be appropriate

venues for vaccination campaigns. Incorporating cholera vaccination into routine vaccination schedules

may be an alternative or complementary strategy to mass vaccination campaigns, for example to reach

young children between campaigns.

Since the documented duration of significant protection for the oral cholera vaccine is 2 years, it is

recommended that initial vaccination with 2 doses be followed by a booster dose every second year. Once

data on the longer-term efficacy of any oral cholera vaccine become available, the recommended interval

between initial and booster vaccination may be extended.

Control of cholera outbreaks The mainstays of control measures to be implemented during ongoing epidemics should remain (i)

providing appropriate treatment to people with cholera, (ii) implementing interventions to improve water

and sanitation and (iii) mobilizing communities.

Pre-emptive vaccination should be considered by local health authorities to help prevent potential

outbreaks or the spread of current outbreaks to new areas. Finalizing of predictive risk-assessment tools to

help countries determine when pre-emptive cholera vaccination might be used is needed urgently; these

tools should be made available and field-tested as soon as possible.

Given the recent large and prolonged outbreaks of cholera (for example, in Angola and Zimbabwe),

reactive vaccination could be considered by local health authorities as an additional control measure,

depending on the local infrastructure and following a thorough investigation of the current and historical

epidemiological situation, and clear identification of geographical areas to be targeted.

The 3-step decision-making tool developed for crisis situations26

should guide health authorities in their

decisions on whether or not to use cholera vaccine during complex emergencies:

8

9

Fig 1 Decision-making tree for Oral cholera vaccine use in complex emergencies.26

Source: Oral cholera vaccine use in complex emergencies: what next? WHO Meeting Report 2005 http://www.who.int/cholera/publications/cholera_vaccines_emergencies_2005.pdf

Considering the lack of experience with implementing reactive vaccination against cholera, the feasibility

and impact of vaccination in halting ongoing outbreaks should be documented and widely disseminated.

Vaccination should cover as many people as possible who are eligible to receive the vaccine (for

example, children aged ≥1 years or ≥2 years, depending on the vaccine), and should be conducted as

quickly as possible.

Surveillance It is strongly recommended that surveillance for microbiologically confirmed cases of cholera be

instituted and integrated into already existing surveillance systems or networks to measure the burden of

disease and monitor the seasonality and the impact of vaccination and other interventions in high-risk

populations.

10

Previous experience of OCV use in mass vaccination campaigns (Excluding randomized clinical trials)

Mass vaccination campaigns using oral cholera vaccines have been documented on 12 occasions over the

last 15 years, either pre-emptively in endemic settings (n=3) or in post-crisis situations (n=4), or

reactively as part of the response to a cholera outbreak (n=5). Vaccine effectiveness observed after

vaccination campaigns was between 78% and 84% after the second dose at 5-6 months

In cholera endemic settings, Vietnam has included an OCV component in its strategy to control cholera

since 1998 and has by far the largest experience of using OCVs as a public health tool. Zanzibar took a

similar decision in 2012 after piloting the project on a small scale. The other pre-emptive uses of OCVs

that have been documented so far were essentially demonstration or pilot projects aimed at testing the

feasibility of mass campaigns (Mozambique). When used in the context of complex emergencies, no

cholera outbreak was reported following pre-emptive vaccination campaigns.

Reactive mass vaccination campaigns with OCVs in response to outbreaks have been organized up to 1

year after the report of the first cases of cholera. Although their impact remains difficult to evaluate for

the time being, vaccine effectiveness was high when evaluated and cholera cases were absent or

decreased in most vaccinated areas. Where reported, acceptance of OCVs by the communities targeted for

vaccination was good, in both endemic and epidemic settings. The most commonly reported constraints

are logistic and mention the important volume of the vaccines and the corresponding cold room storage

capacities, and the handling of buffer / water during delivery. With 2 exceptions, reported from very

specific contexts, the cost of delivery varies between $0.5 and $2.5 per fully immunized person.

Cost effectiveness studies were conducted in several endemic countries and concluded that cholera

vaccination would be “cost effective” particularly when targeting children27

or when herd protection is

taken into account.28

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Table 2 Historical summary of mass vaccination campaigns using oral cholera vaccines (excluding randomized clinical trials)

Location/dates Situation Target

population

Vaccine

used

No. persons

vaccinated

Vaccine

coverage

Costs per fully

immunized

Vaccine effectiveness

(VE) and potential impact

Pre-emptive mass vaccination campaigns in endemic settings

Vietnam (1998

to present)29,30

Endemic area.

Yearly

campaigns used

pre-emptively

before the peak

cholera season to

control endemic

cholera in high-

risk areas and

also used pre-

emptively during

floods

Children 1-15

years old, and

residents of all

ages during

floods

ORC-Vax®

Vietnamese

killed OCV

>20 million

doses

delivered

From 75% to

95%, for 2

doses

depending on

years and

place

Vaccine

price/dose: $0.4

VE of 50% at 3 to 5 years

12

Location/dates Situation Target

population

Vaccine

used

No. persons

vaccinated

Vaccine

coverage

Costs per fully

immunized

Vaccine effectiveness

(VE) and potential impact

Beira,

Mozambique

(2003/04)31,32

Endemic area

with frequent

outbreaks

Campaign before

rainy season.

>2 years old

residents

(n=19,550)

Non-pregnant

Dukoral® > 98,000

doses

delivered

53,700

received 1

dose; 44,000

received 2

doses

(including

many outside

the targeted

area)

54% fully

immunized in

targeted area

$2.1per fully

immunized

(vaccine

shipment and

delivery).

Vaccine

donated

VE between 78% and 84%

for two doses over a five-

month period

Zanzibar

(2009) 33-35

Endemic area

with frequent

outbreaks

>2 years old

among 48,178

inhabitants

Non-pregnant

Dukoral® 23,921

persons

received 2

doses

50% fully

immunized

$25.3 per fully

immunized

($20.0 for the

vaccines + $5.3

for delivery)

VE of 79% 15 months after

the campaign for recipients

of 2 doses

Evidence of herd protection

Pre-emptive use in post-crisis situations

Uganda

(1997)36,37

Stable refugee

setting

Around 44,000

refugees in 6

Dukoral® >35,000 for

1st dose;

83% for 1st

dose; 76% for

$0.53 per fully

immunized for

No cases reported from the

vaccinated settlements

13

Location/dates Situation Target

population

Vaccine

used

No. persons

vaccinated

Vaccine

coverage

Costs per fully

immunized

Vaccine effectiveness

(VE) and potential impact

camps 27,600 for 2nd

dose

2nd

dose

delivery.

Vaccine

donated

during a cholera outbreak

in the district one year after

the campaign

Darfur, Sudan

(2004)38,26

Stable refugee

setting

>2 years old

among >53,000

IDPs in 2

camps

Dukoral® 47,302 IDPs

received 2

doses

87% fully

immunized

$7.1 per fully

immunized,

including $0.7

for delivery

N/A

No outbreak reported

Aceh, Indonesia

(2005) 38,39

Complex

emergency

following

tsunami

≈79,000 IDPs

living in camps

in 3 areas

Dukoral®

54,627

received 2

doses

69% fully

immunized

$17.6 per fully

immunized,

including $8.2

for delivery

N/A

No outbreak reported

Haiti (2012)40

Post-earthquake

and nationwide

cholera outbreak

≈70,000

residents of 2

rural areas > 1

year old.

Shanchol™ 41,193

received 2

doses

76.7% and

62.4% fully

immunized

$3.33 per dose

administered

including $2.13

for vaccine and

$1.20 for

delivery

N/A

Reactive campaigns during cholera outbreaks

Micronesia Ongoing > 2 years old Orochol® N/A 47% of target $1.23 per VE of 79%

14

Location/dates Situation Target

population

Vaccine

used

No. persons

vaccinated

Vaccine

coverage

Costs per fully

immunized

Vaccine effectiveness

(VE) and potential impact

(2000)41

outbreak on the

island since 5

months

among 34,486

residents non-

pregnant

single-dose

live-

attenuated

CVD 103-

HgR vaccine

(not

marketed

anymore)

population person

vaccinated for

delivery

Decrease of cholera attack

rate

Not spread to surrounding

islands

Mayotte

(2000)42-44

Ongoing

outbreak in the

archipelago

since 1 year

Sporadic cases

on the island

since 9 months

>2 years old

among 175,000

residents and

illegal migrants

Dukoral®

93,000

persons

vaccinated

64% 26.9€ per

person

vaccinated (all

included), i.e.

about $24.5 in

2000

Only sporadic cases

reported after the campaign

Marshall islands

(2000)45

Ongoing

outbreak on the

island since < 1

month

Vulnerable

groups among

9345

inhabitants

Orochol®

N/A 32% total

population

N/A Outbreak ended during the

month following the

campaign and did not

spread to surrounding

islands

15

Location/dates Situation Target

population

Vaccine

used

No. persons

vaccinated

Vaccine

coverage

Costs per fully

immunized

Vaccine effectiveness

(VE) and potential impact

Hanoi, Vietnam

(2008)46

Ongoing

outbreak in an

urban setting

since 3 months

462,570

residents of 2

hard hit districts

age >=10 years,

non-pregnant

ORC-Vax®

Vietnamese

killed OCV

N/A 80% for at

least one dose

N/A VE of 76% for at least one

dose 3 to 4 months after the

campaign.

New wave of the outbreak

reported 3 months after the

campaign

Guinea Conakry

(2012) 47

Ongoing

outbreak in a

rural setting

since 3 months

>1 year old

among

≈200,000

residents of 2

rural districts.

Non-pregnant

Shanchol®

Controlled

Temperature

Chain (CTC)

strategy was

used on the

day of

vaccination.

172,544 for

1st dose,

143,706 for

2nd dose

76% fully

immunized,

>90% with at

least one dose

$7.4 per fully

immunized

($4.9 for the

vaccines + $2.5

for airfreight

and delivery

Cost per dose of

vaccine

delivered $2.89

incluisng £1.85

for the vaccine

and $1 for

direct costs

VE of 84% for 2 doses

6 months after vaccination

(Data analysis ongoing

Luquero F)

Cases remained low in

vaccinated districts during

rainy season compared to

other parts of Guinea

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Stockpile mechanism overview

The OCV stockpile has been created on the principle that vaccines have a role in the prevention and

control of cholera outbreaks when used in conjunction with accessible healthcare and improvements in

water and sanitation. It has also been established with the understanding that the stockpile will have a

limited number of doses relative to the need for vaccine and that the use of OCV through the stockpile

will not significantly alter global cholera disease trends. However, evidence generated through

stockpile OCV use may help indicate the vaccine’s potential to control outbreaks and to impact

disease trends when used on a larger scale.

Given the limited global supply of licensed, WHO-prequalified cholera vaccines, a global stockpile is

likely to improve the timely access of OCV for countries that may benefit from its use. Moreover,

increased OCV use may lead to a larger global vaccine supply through more consistent and predictable

demand for vaccine.

Objectives of OCV stockpile

The use of the vaccine in emergency response situations is expected to help reduce cholera morbidity

and mortality in epidemic situations and alleviate the disease burden on at-risk populations.

While vaccines provide a short-term effect as an immediate intervention to a potential cholera

outbreak, expanding access to improved drinking-water sources and sanitation constitutes a longer-

term solution for most waterborne diseases, including cholera.

The use of OCV from the stockpile should not detract attention from the key established responses to

cholera outbreaks, which are: detection, diagnosis, and treatment of cases with oral rehydration and

antibiotic treatment; establishment of a safe water supply; and implementation of adequate waste

disposal and sanitation.

The main objective of the OCV stockpile is to ensure the timely and targeted deployment of

OCV such that vaccine can be used as an effective outbreak response where it is most needed.

17

Use of the stockpile

The main use of this stockpile will be for outbreak response, either in the form of reactive

campaigns in areas experiencing an active outbreak or pre-emptive vaccination campaigns

among populations at elevated risk for cholera due to outbreaks in adjacent areas or at

heightened vulnerability due to humanitarian crisis.

Reactive vaccination occurs after the start of an outbreak and aims to limit the extent of the outbreak

in communities at imminent risk (i.e., neighbouring communities - across borders, or linked by river

systems or water and sanitation systems), provided the local infrastructure allows it, and an in-depth

analysis of past cholera data and identification of a defined target area have been performed.48,49

“An outbreak of cholera at the national level commonly consists of a succession of several outbreaks

as it spreads through the country or across borders. Vaccinating communities in areas at imminent risk

during such a succession would have greater impact than in areas where the transmission has already

been active for several weeks or months. Many of the individuals in a community where there is active

transmission may have already been infected with cholera even if they are asymptomatic. In fact, an

estimated 80 per cent of infected individuals will be asymptomatic but still shed the bacteria. This

reactive strategy is particularly important in areas where response mechanisms cannot deliver typical

cholera control measures” 49

Pre-emptive vaccination of populations takes place before likely upsurges in cholera transmission or

outbreaks. It may be considered, based on risk assessment and epidemiological data, to limit the spread

of outbreaks to new areas at risk.

Ideally pre-emptive and reactive vaccination, during an outbreak response, should cover as many

people as possible who are eligible, and should occur as quickly as possible.

Management and governance of the OCV stockpile for emergency response7

The International Coordinating Group (ICG) comprising Médecins Sans Frontières (MSF), the

International Federation of Red Cross and Red Crescent Societies (IFRC), the United Nations

Children’s Fund (UNICEF), and WHO will be the decision-making body for deployment of OCV

through the stockpile. This group also coordinates vaccine release from the international Yellow Fever

and Meningococcal vaccine stockpiles.

18

Additional expertise and technical advice might be sought on a case-by-case base from a range of

partners. A meeting with participation of key stakeholders is organized annually.

The ICG manages the global stock, liaison with manufacturers and 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. The

ICG mechanism has also contributed to reinforce surveillance and laboratory confirmation since

countries must demonstrate an ongoing epidemic to access the ICG stockpile.

The OCV stockpile initially comprises two million doses of vaccine per year for an initial period of 2-

3 years (2013 – 2015). Start-up funding for the stockpile will be provided by donors. A revolving fund

will be established as with other ICG stockpiles, to assure longer-term financial stability.

Collected funds will support the procurement of vaccine, country preparedness and planned

operational costs for the use of the OCV stockpile vaccination campaign and evaluation of the

stockpile mechanism initial period of 3 years.

After an intermediate evaluation, an extension could be made up to 5 years with additional

investments and/or with funds generated through the revolving fund mechanism.

Application procedure to OCV in IGC stockpile

Vaccine requests may be made by any national or international organization, and the ICG will provide

a decision of approval or denial of vaccine release within 48 hours of request receipt, depending on

whether additional information is required. Vaccine and supplies then will be deployed if approved

(Fig 2).

The minimum situational requirements for a request to be considered are:

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. Diagnosis of

cholera is confirmed by isolating V. cholerae O1 or O139 from faeces through laboratory testing.

To ensure the quality of samples, Cary Blair transport medium should be used for transport and

storage of rectal swabs.

19

An OCV campaign has NOT 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).

20

Figure 2- Request process and roles of ICG and partners

Decision criteria for the release of OCV

Once an outbreak of cholera has been laboratory confirmed in a given area, a number of indicators

may be considered to estimate the projected severity of the cholera outbreak and the potential

impact of the vaccination campaign.

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: (table 3)

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

21

(e.g. mobility; health-seeking behaviours; 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.

The list of indicators presented in Table 3 will be used to inform decision-making but none should

be considered sufficient to make a final decision.

Deployment of vaccines from the OCV stockpile will also take into consideration programmatic

factors such as the local capacity to organize a campaign and the prevailing security

conditions.

Table 3: Epidemiological and demographic considerations for OCV stockpile deployment7

Criterion Indicator Decision threshold Potential

impact of

vaccination

campaign

High Low

Susceptibility of

the population

Number of cases reported in the

affected area(s) during the past 2–

3 years

No or few cases

reported

X

High number of cases

reported

X

Attack rate of previous outbreaks

in the affected area(s)1

High attack rate X

Low attack rate X

Vulnerability of

the population

Case-fatality rate (CFR) of

previous outbreaks in the affected

area(s)2

High CFR X

Low CFR X

1 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)50 guidelines, 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. 2 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.51

22

Refugee camp, internally

displaced people, or slums present

in the affected area(s)

Yes X

No X

Area(s) with important population

movements (border, market hub,

etc.)

Yes X

No X

Population density in the affected

area(s)

High density X

Low density X

Access to water, sanitation, and

hygiene

Poor access X

Good access X

Risk of spatial

extension

Time elapsed / maturity of the

outbreak since first case reported3

Few weeks X

Few months X

Attack rate since the start of the

current outbreak (i.e. cumulative

cases)1

Low attack rate X

High attack rate X

Proportion of health units in the

district reporting cases4

Low proportion X

High proportion X

Time at which first cases were

notified during the epidemic

season5

First cases notified

early in the season

X

First cases notified late

in the season

X

3 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 weeks52 4 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). 5 In some areas, cholera outbreaks occur on a regular basis, every year or so, usually during the rainy season

23

Monitoring and evaluation of the OCV stockpile

While there is evidence that the use of OCV in pre-emptive and preventive campaigns will have a

positive impact on reducing mortality and morbidity, there is currently insufficient evidence to

determine the role of the vaccine in outbreak response.

Given the limited global supply of OCV compared with the potential need, it will be crucial to

document the impact of the stockpile on cholera prevention and control plans and on disease burden,

both locally and globally.

Documenting both the decision and outcomes of use or non-use of OCV will also be vital to

developing evidence-based guidance and strengthening recommendations for future OCV use.

To address this need a rigorous system for monitoring and evaluating should be embedded within the

OCV stockpile mechanism.53

Findings will be reported to all relevant stakeholders, including stockpile decision-makers, past and

potential requesting countries or organizations, donors, and technical partners.

As one of the objectives of the 3 years period stockpile is to gather the evidence of the impact of

vaccination on cholera epidemics, countries requesting access to OCV-ICG stockpile will be requested

to implement and/or provide the necessary data for M&E purpose. Specific M&E protocols will be

available for their implementation.

24

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