4.7 Vaccination strategies

4.7.1 General considerations for oral cholera vaccine (OCV) use

Vaccination against cholera is carried out in three contexts:

• In response to cholera outbreaks (reactive vaccination);
• During humanitarian emergencies when the risk of an outbreak is high (pre-emptive vaccination);
• In endemic areas, prior to the cholera season (preventive vaccination).

 

The decision to vaccinate will rely on a risk assessment (risk of an outbreak or outbreak extension, or high morbidity in the event of an outbreak), and an estimation of the feasibility of a vaccination campaign a Citation a. The WHO provides a tool for assessing risk and feasibility: Oral cholera vaccines in mass immunization campaigns: guidance for planning and use. 2010, Annex 1.
http://whqlibdoc.who.int/publications/2010/9789241500432_eng.pdf  .

 

Vaccinating entire populations is not feasible and not necessary unless the population is small and the risk of exposure is uniformly high. Priority should be given to areas with a history of, currently experiencing, or at risk of high attack and case fatality rates.

 

When a target population has been identified, everyone 12 months of age and over should be vaccinated. The use of OCV in pregnant women should be discussed with health authorities. The WHO recommends the vaccination of pregnant women as the benefits greatly outweigh the risks [1] Citation 1. World Health Organization. Cholera vaccines: WHO position paper. Weekly Epidemiological Record 2010; 85:117-128. ^, [2] Citation 2. World Health Organization. Technical Note: Evidence of the risks and benefits of vaccinating pregnant women with WHO pre-qualified cholera vaccines during mass campaigns, 13 January 2016. 
http://www.who.int/cholera/vaccines/Risk_Benefits_vaccinating_pregnant_women_Technical_Note_13Jan2016.pdf .

 

Check with health authorities that the cholera vaccination campaign will not take place within 2 weeks of a mass vaccination campaign against poliomyelitis. More information is needed on coadministration of OCV with oral polio vaccine.

 

Vaccination should be preceded by a community information and awareness raising campaign, directed at the target population, paying specific attention to groups usually underrepresented in vaccination campaigns such as adult males.

4.7.2 Vaccination in response to an outbreak

Evaluation of the potential impact of reactive vaccination

The potential impact of vaccination should be estimated by using the demographic and epidemiologic criteria established by the International Coordinating Group (ICG) on vaccine provision (Table 4.1).

 

Table 4.1 - Considerations for OCV stockpile deployment during an on-going epidemic (adapted from the WHO [3] Citation 3. World Health Organization. Guidance on how to access the Oral Cholera Vaccine (OCV) from the ICG emergency stockpile, Geneva, 2013.
http://www.who.int/cholera/vaccines/Guidance_accessing_OCV_stockpile.pdf?ua=1 )

 

Criteria	Indicators	Decision threshold	Potential impact of vaccination campaign
			High	Low
Susceptibility of the population in the affected area(s)	Number of cases reported during the past 2-3 years	No or few cases (a) Citation a. Less natural immunity through recent exposure.	X
		High number of cases		X
	Attack rate (AR) of previous outbreaks	High AR	X
		Low AR		X
Vulnerability of the population in the affected area(s)	Case-fatality rate (CFR) of previous outbreaks	High CFR	X
		Low CFR		X
	Refugee camp, internally displaced people, or slums	Yes	X
		No		X
	Area(s) with large movements of population (border, market hub, etc.)	Yes	X
		No		X
	Population density	High density	X
		Low density		X
	Access to water, sanitation, hygiene, and curative care	Poor access	X
		Good access		X
Risk of spatial extension	Time elapsed since first case reported	Few weeks	X
		Few months		X
	Attack rate since the start of the current outbreak (cumulative cases)	Low attack rate (b) Citation b. More susceptible people may benefit from vaccination.	X
		High attack rate		X
	Proportion of health units in the district reporting cases	Low proportion	X
		High proportion		X
	Time at which first cases were notified during the epidemic season	Early in the season	X
		Late in the season		X

If the assessment indicates that a campaign is likely to achieve a reasonable reduction in morbidity and mortality and if this campaign is feasible (Section 4.7.3), the next step is to decide who to vaccinate. Two groups may be targeted for a vaccination campaign: the population currently affected by cholera and the population highly vulnerable to an expansion of the outbreak. These two groups are not necessarily mutually exclusive.

Selection of the target population(s)

Several factors will influence the choice of the target population(s) for vaccination:

 

• Risk of mortality

The main factor in guiding selection of a target population for vaccination is the risk of cholera mortality (whether in the currently affected or at-risk populations), particularly when there is less vaccine available than required. Analysis of current and historic data may indicate that vaccination of an unaffected population which is at high risk of a severe epidemic and high mortality is potentially more beneficial than vaccination of a currently affected population that is at less risk of poor outcome.

 

• Phase of the outbreak

As an outbreak evolves, the proportion of people in the affected population who remain susceptible and at risk of exposure will decrease, as will the proportion benefitting from reactive vaccination.

Ideally, then, vaccination of an affected population should occur in the early phase of the outbreak, when the number of cases is still rising. However, experience to date has demonstrated that rapidly achieving vaccine-induced immunity in a population early in an outbreak is challenging. Prompt decision-making, vaccine acquisition, and campaign implementation considerably reduces the delay.

Vaccinating late in the epidemic would likely add little to the preventive measures already being implemented in water, sanitation and hygiene. In this context, vaccinating populations still at risk of outbreak extension is preferable. Vaccination of the affected population near or after the peak can be the right strategy in the following scenarios:

• Severe epidemic with attack rate and/or mortality rate clearly above the norm;
• Epidemic likely to be prolonged (i.e. starting prior to the typical season);
• Prolonged epidemic, presenting ongoing risk of outbreak extension to other vulnerable populations

 

• Access to treatment and clean water/sanitation/hygiene

Morbidity and mortality will likely be low if the health system and partners are able to provide treatment facilities, clean water and improve sanitation and hygiene within a reasonable time frame. Greater benefit may be realized by vaccinating populations which will not have such support, whether currently affected or not.

 

• Population movement

Vaccinating non-affected populations may be a priority when there is a large influx of people coming from an area with a cholera outbreak.

 

There are no completed field studies which show strong evidence for prioritizing one target population over another. Currently, these recommendations are made based on observations of cholera epidemics and the relatively limited experience of vaccinating in the outbreak setting. In the end, the guidance here is only a subset of the considerations that local and national health authorities may use in a final decision on the strategy of vaccination.

4.7.3 Vaccination in humanitarian emergencies b Citation b. For more information, see Vaccination in acute humanitarian emergencies: a framework for decision making. Geneva, Switzerland: World Health Organization; 2017.
http://apps.who.int/iris/bitstream/10665/255575/1/WHO-IVB-17.03-eng.pdf

 

Vaccination is aimed at protecting a vulnerable population when the key elements of cholera control are lacking and unlikely to be established at sufficient scale within a reasonable time frame.
However, vaccination does not lessen the need for protection against water-borne diseases and should not replace provision of clean water and proper sanitation.

 

The decision to vaccinate will be based on an analysis of:
1. The actual risk of cholera based on the current and historical epidemiological situation;
2. The capacity to control a possible outbreak and provide adequate care to prevent high mortality;
3. The feasibility of, and the capacity to organize, a vaccination campaign.

1. Actual risk of an outbreak

The risk of a cholera outbreak in humanitarian emergencies is high when several of the following risk factors are combined.

 

Table 4.2 - Risk factors for cholera outbreak in a humanitarian emergency

 

For example:

• In a non-endemic area, the risk is high if sanitation and water conditions have seriously deteriorated and cholera is present in a neighbouring country.
• In an area where cholera occurs regularly, the risk is high if a large number of people move to an unorganized, overcrowded refugee camp or slum.

2. Capacity to control a possible outbreak and/or limit cholera mortality

Outbreak and/or mortality control is difficult to achieve if some of the following factors are present.

 

Table 4.3 - Main challenges for adequate cholera control

 

 

3. The feasibility of and the capacity to organize a vaccination campaign

Challenges for organizing an OCV vaccination campaign in humanitarian emergencies − and also in response to an outbreak − include:

• Limited global stock of OVC with respect to the number of people who might benefit from vaccination.
• Long time interval between the decision to vaccinate until the completion of the second round:
  • 1 week to complete ICG proposal with required context, epidemiologic, and demographic information and receive the initial ICG response (48 hours maximum after receiving complete request);
  • 1 to 2 weeks for transportation of OCV and clearance through customs and completion of campaign organization: cold chain, transport, staff recruitment and training, information campaign, site set up, etc.;
  • 4 weeks for the vaccination campaign itself with 2 rounds (plus a 3rd catch-up round in some cases) with a minimum interval of two weeks between the rounds;
  • 1 week to obtain long-lasting immunity following the second dose.
• Other high priority public health interventions limiting resource capacity for OCV campaign.
• Difficulty to achieve adequate coverage with a two-dose regimen in a highly mobile population.
• Large capacity of cold chain required for OCV.

 

However, if a single-dose strategy is used (Section 4.7.5), twice as many people can be vaccinated even with a limited stock of vaccines and the time required for vaccinating is significantly shortened.

4.7.4 Preventive vaccination in endemic settings

OCV is useful for populations for whom cholera is a significant persistent public health matter. The principal targets for vaccination are populations at high risk, as determined by analysis of historical data. If vaccine availability is limited, only specific sub-populations at highest risk of symptomatic disease and poor outcome (pre-school or school children, pregnant women, those with HIV-infection and the elderly) can be targeted [4] Citation 4. Weekly epidemiological record/Relevé épidémiologique hebdomadaire. 26 MARCH 2010, 85^th YEAR / 26 MARS 2010, No. 13, 2010, 85, 117–128.
http://www.who.int/wer/2010/wer8513.pdf .

 

Vaccination of populations living in locations known for the propagation of epidemics may serve to prevent more regional spread and the need to vaccinate more widely. These populations are those living close to natural reservoirs of cholera (lakes, etc.) and transportation or trade centers.
Vaccination should be planned at a time of year where there is little or no cholera transmission.
Re-vaccination might be required after vaccine immunity decreases if definitive measures to improve access to safe water and sanitation have not been implemented.

4.7.5 Single dose strategy

In epidemic and humanitarian emergency contexts, the priority is to provide rapid protection to as much of the at-risk population as possible. With a vaccine given in 2 doses at least 2 weeks apart, and that is in limited supply with respect to needs, a single dose strategy has been employed.

 

Systemic immune response studies have shown that OCV stimulates a strong response after one week with the first dose in a significant majority of individuals in an endemic setting [5] Citation 5. Saha A, Chowdhury MI, Khanam F, et al. Safety and immunogenicity study of a killed bivalent (O1 and O139) whole-cell oral cholera vaccine Shanchol, in Bangladeshi adults and children as young as 1 year of age, Vaccine 29 (2011), 8285-92. ^, [6] Citation 6. Kanungo S, Paisley A, Lopez AL, et al. Immune responses following one and two doses of the reformulated, bivalent, killed, whole-cell, oral cholera vaccine among adults and children in Kolkata, India: A randomized, placebo-controlled trial, Vaccine (2009), Nov 16;27(49):6887-93. ^, [7] Citation 7. Kanungo S, Desai SN, Nandy RK, et al. Flexibility of Oral Cholera Vaccine Dosing—A Randomized Controlled Trial Measuring Immune Responses Following Alternative Vaccination Schedules in a Cholera Hyper-Endemic Zone. PLoS Negl Trop Dis (2015), 9(3): e0003574.
http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003574 .

 

In a clinical trial, a single dose protocol demonstrated significant protection (compared to placebo) over a short period (6 months), principally against severe cholera in the adult population [8] Citation 8. Qadri F, Wierzba TF, Ali M, et. al., Efficacy of a Single-Dose, Inactivated Oral Cholera Vaccine in Bangladesh, NEJM 2016, 374(18), 1723-32.
http://www.nejm.org/doi/full/10.1056/NEJMoa1510330 . A case-control study performed following a single dose reactive vaccination campaign confirmed substantial short term protection [9] Citation 9. Andrew S Azman, Lucy A Parker, John Rumunu et al. Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study. The Lancet Global health. Volume 4, No. 11, e856–e863, November 2016.
http://www.thelancet.com/journals/langlo/article/PIIS2214-109X%2816%2930211-X/fulltext .

 

Thus, a vaccination with a single dose is possible when long term protection is not the immediate priority. Twice as many people can be vaccinated with the same quantity of vaccines thus herd protection is enhanced when coverage is high. However, in a context requiring long-term protection the two-dose regimen is preferable.

 

For practical points for oral cholera vaccination campaign, see Appendix 10.

4.7.6 Vaccination campaign strategies

Vaccination can be accomplished by fixed teams, mobile teams, and door-to-door. Depending on the context, a mix of the three may be necessary.

 

A rapid time frame is desirable for each round when vaccinating in response to an outbreak. A catch-up round may be implemented to vaccinate those who have missed the first or second dose.

Fixed sites

Fixed sites are appropriate when an entire village or city is targeted. The size and number of the teams depend on the number of people expected per day. The first day of the round is often when the most people will attend.

Mobile teams

Mobile teams can be used when small populations are targeted and the number of expected people can be vaccinated within a few hours (e.g. children in schools) or to target people unable to get to the fixed vaccination points during the day (e.g., men at the workplace).

Door-to-door

Door-to-door vaccination may be appropriate where there is local experience with this approach (e.g. polio).
This strategy may be particularly useful when vaccinating a specific sub-population (i.e. a neighbourhood at particularly high risk) without needing to vaccinate an entire city.
Knowing the number of residents or households within the target area is helpful. Keeping track of those absent during each round facilitates targeting during catch-up rounds.
With this approach, people unable to walk to the fixed vaccination points (e.g. the elderly or disabled) can be vaccinated as well.

4.7.7 Post vaccination assessment

After any vaccination campaign, two types of studies should be performed. These studies should be planned from the beginning and conducted by specialized study teams.

• A vaccination coverage survey, as calculating the proportion of people vaccinated among the total target population (administrative coverage) does not permit an accurate determination of vaccine coverage.
• A vaccine effectiveness study, to determine how the vaccine protects against cholera in the specific context and population (e.g., background immunity, HIV prevalence). Effectiveness studies require that cholera transmission occurs during the planned period of study. This may not always be the case, particularly for vaccination in humanitarian emergencies.