Assessing the Feasibility of Implementing Mass Vaccination Campaigns Using Oral Cholera Vaccination
Conrad Flaczyk Department of Bioresource Engineering, McGill University, Montreal, Canada
Dr. Jan Franklin Adamowski Department of Bioresource Engineering, McGill University, Montreal, Canada
The 2010 Haitian cholera epidemic exposed major weaknesses in the traditional approach to cholera remediation. As a result, the World Health Organization (WHO) revised its cholera-response guidelines in 2011 to recognize Oral Cholera Vaccination (OCV) as a viable cholera control mechanism. The WHO currently recommends that OCVs be administered in conjunction with existing interventions for cholera remediation. Although OCVs have satisfied clinical trials, few studies have investigated the feasibility of implementing mass OCV campaigns in endemic regions; there remains considerable debate about cost-effectiveness, logistical challenges, and acceptability of OCVs by local populations. The author of this article aims to assess the feasibility of implementing mass OCV campaigns in cholera-endemic regions. He outlines three recommendations for the successful implementation of such campaigns: (1) building local capacity and educating populations about cholera prevention techniques during OCV campaigns; (2) developing affordable vaccines, subsidized by international communities; and (3) using qualitative research methods to understand local socio-cultural variables before OCV campaigns.
Cholera continues to pose a significant public health burden for many regions of the world that have restricted access to basic sanitation infrastructure. Cholera is an acute and highly infectious diarrheal infection that is caused by the bacterium Vibrio cholerae.[1,2] The main symptoms of cholera infections are characterized by extensive watery diarrhea and vomiting. If left untreated, cholera infection can result in severe dehydration within a couple of hours, leading to shock and/or death in some cases.
According to the 2012 World Health Organization (WHO) Report on Cholera,  1.4 billion people worldwide are at risk of cholera infection. Moreover, the WHO reports that there are approximately 2.8 million cholera infections each year and approximately 91,000 deaths in cholera-endemic countries worldwide [3,4] The WHO also reports that since 2000, the absolute number of cholera incidence has been increasing worldwide, [2,3] in addition to the proportion of cholera infection worldwide. [2,3] Note that the 2010 Haitian cholera epidemic accounts for a significant proportion of cholera infections and death during that period. Between October 2010 and May 2013, Haiti reported over 600,000 cases of cholera infection and more than 8,000 deaths. 
In the light of the 2010 Haitian cholera epidemic, the World Health Assembly in 2011 declared that cholera is a global priority and called on the international community to re-evaluate its approach to cholera remediation.  Traditionally, cholera remediation efforts focused on the widespread provision of clean drinking water and basic sanitation infrastructures.  While these efforts are necessary to treating existing cholera infections, they are not sufficient in remediating acute cholera epidemics.  The 2010 Haitian cholera epidemic is one case that highlighted major limitations to the traditional approach. As a result, the WHO revised its cholera-remediation guidelines in 2011. 
Under the more recent guidelines, the WHO recognizes Oral Cholera Vaccination (OCV) as a viable cholera remediation strategy. At present, two OCVs are qualified and licensed by the WHO: Dukoral and Shanchol. [6,7] Clinical trials conducted in 2011 in Kolkata, India, found that Shanchol is 65% effective in preventing cholera infection five years after vaccination.  Both vaccines are administered as a two-dose regimen and both have been proven safe in the laboratory.  Today, the WHO recommends that OCVs be administered in cholera-endemic regions in conjunction with traditional interventions.
While OCVs have satisfied the WHO’s clinical trials, there remains considerable debate regarding the feasibility of implementing mass OCV campaigns in cholera-endemic regions of the world. [1,4,8] The main questions in this debate center around cost-effectiveness, logistical challenges, and acceptability of OCVs by local populations. [9,10] Few studies have considered the socio-cultural determinants that can influence the results of OCV campaigns. Consequently, this paper aims to fill that gap by reviewing the current knowledge on mass vaccination campaigns in developing regions.
Since OCVs have only been proposed in the last decade, real-world, practical experience with OCV campaigns is limited.  Much of the real-world experience with OCV campaigns comes from small-scale cholera interventions in Asia. [11-14] The first major study on a large-scale OCV campaign was published in 2013 by Ciglenecki and colleagues. It described the large-scale OCV campaign implemented in Guinea between April 2012 and June 2012. It was initiated to control an acute cholera epidemic in Guinea. A total of 312,650 doses of vaccine were administered and it was the first time that Shanchol vaccine was administered to control an acute cholera epidemic.  Overall, Ciglenecki and colleagues found that the campaign was generally well received by local populations. High vaccination coverage was achieved, despite the short preparation time. They found that feasibility, timeliness of implementation, and delivery costs, were similar to those of other mass vaccination campaigns. 
More recently, Kar et al.  conducted a study accessing the feasibility of using Shanchol vaccine in a mass vaccination campaign, while relying almost exclusively on local public-health infrastructures. They found that mass vaccination campaigns using Shanchol are viable, however, require detailed micro-planning. The authors suggest that before implementing a mass vaccination campaign using Shanchol, it is necessary to implement social mobilization activities to engage local stakeholders. For instance, the authors recommend that a detailed micro-plan be developed in consultation with local health volunteers and community leaders.  This was achieved by meeting with public health officials and making site visits before the campaign. The authors suggest that cost is a major barrier to the successful implementation of OCV campaigns. They therefore argue that the costs of a campaign must significantly be reduced through planning.
Socio-cultural determinants must also be considered before implementing mass OCV campaigns. Emerging literature on the topic suggests that the success of such campaigns largely depends on the unique socio-cultural determinants of the populations. Almost unanimously, higher education was associated with an increased willingness to participate in remediation treatments.  Merten et al.  studied the effects of education on the local population’s willingness to pay for OCVs. They found that level of education influenced vaccine acceptance at all price levels. Not surprisingly, they found that higher educated populations were willing to pay a price premium for OCVs. Nevertheless, at the highest price levels, “material insecurity” was more predictive than education.
According to Merten et al.,  the price of the vaccine is the most important determinant of program participation in cholera-endemic regions. Consequently, they investigated local perceptions of acute diarrhea illness and anticipated vaccine acceptance in two sites within the Democratic Republic of Congo. 360 randomly selected adults were interviewed through a semi-structured questionnaire. Anticipated vaccine acceptance at ‘no cost’ was approximately 97%. At lower costs (free - $5 USD), anticipated vaccine acceptance is relatively high at more than 80% acceptance. These findings suggest that mass OCV campaigns are viable when the vaccine is relatively affordable. 
'program participation in Kolkata, India, was lowest on Thursdays'
In another study by Merten et al. , community acceptance of OVC campaigns was assessed. The authors argued that while price is the most important determinant of program participation, several other contextual determinants can influence the success of the campaign. These contextual determinants must be deeply understood before initiating the campaign. For instance, Kar et al.  found that program participation in Kolkata, India, was lowest on Thursdays. They attribute this to the Hindu culture, which prohibits eating meat on Thursdays. Through semi-structured interviews, the implementation team found that some local participants feared that vaccines contain animal by-products.
Several studies have investigated the role of vaccination campaigns in educating local populations and building capacity. In recent a study, Aibana et al.  examined the effectiveness of including an educational component in OCV campaigns. The authors conducted surveys before and after an OCV campaign in rural Haiti to assess the impacts of the campaign on the wider community. The authors documented a substantial increase in the rate of sanitary practices used in the community, such increased hand-washing, the cooking of foods, and decreased drinking of untreated water. Similarly, Beau De Rochars et al.  found major improvements in the frequency of water treatment practices in Haiti following a mass OCV campaign with an education component. The frequently of water treatment increased from 31% to 74% after the OCV campaign.
CASE STUDY: GUINEA
Guinea regularly experiences cholera endemics during its rainy season in July.6 In February 2012, an early cholera outbreak, coupled with the ongoing cholera endemic in neighboring Sierra Leone, hinted that a possible cholera epidemic was approaching.  Consequently, the Ministry of Health of Guinea, in partnership with Doctors Without Borders, decided to implement a mass OCV campaign. The aim of this campaign was to control the spread of cholera infection by pre-treating high risk populations.
This case-study highlights the potential effectiveness of mass OCV campaigns. The Ministry of Health of Guinea implemented two mass OVC campaigns. The first campaign was situated in the Boffa District, located on the north-west coast of Guinea. The second campaign was situated in the Forecariah District, located on the south-west coast of Guinea. In total, 320,000 OCV doses were administered. These administrations occurred in two sessions, which were spaced over two to three weeks. In both the Boffa and Forecariah Districts, weekly numbers of reported cholera cases were significantly lower than in the country of Guinea overall. 
The relative success of this OCV campaign can be used as a case-study for future cholera remediation efforts. Ciglenecki et al.  attribute the success of this campaign to the low-cost of vaccine administration and to the stakeholder mobilization efforts carried out before the start of the campaign. During the campaign, the cost per dose of vaccine was $2.89 USD, which included $1.85 for the vaccine itself and approximately $1.00 USD for delivery and implementation. As a result of the relatively low treatment cost, program participation was high at nearly 90%.
In terms of capacity building and stakeholder engagement, this case-study serves as an excellent model for a bottom-up approach to mass vaccinations. Prior to the start of the OCV campaign in Guinea, both of the targeted districts were visited by health promoters, who provided the local populations with information about the vaccination. Interestingly, the health promoters were selected in earlier stakeholder mobilization efforts and they were influential leaders in their community.  Together with Doctors Without Borders representatives, the community leaders went door-to-door in an effort to raise awareness for the OCV campaign and answer individual questions.
There remains considerable debate in the literature on whether the implementation of mass OCV campaigns is feasible in cholera-endemic regions. While the literature may be divided on the advantages and disadvantages of mass OCV campaigns, there is an overwhelming agreement that cholera epidemics must be studied in context. Although OCVs may pass clinical trials, this does not necessarily imply that the vaccinations will be effective in practice. As studied by Mazzeo and Chierici,  each social environment is characterized by a complex system of values, beliefs and knowledge. They warn against top-down remediation practices that are removed from context. The first recommendation in this paper is the need to draw on qualitative research methods when developing international remediation strategies. Qualitative research methods enable researchers to develop a fuller understanding of the institutions and processes for promoting social change and improving the health of local populations. [8,16] This is particularly important during cholera epidemics because they are often characterized by a rapid onset and swift progression. For this reason, the need to mobilize people and resources quickly and efficiently is critical to an effective remediation strategy.
Smith examined the challenges to developing partnerships between civil society and international organizations for development.  He argues that the greatest challenges to forming these partnerships are differences in how each group envisions the process and goals for development. Still, these challenges are not insurmountable. [17,18] The Guinea case-study is one example of how international organizations and NGOs can work to engage local populations. Doctors Without Borders partnered with local community leaders to raise awareness for cholera vaccination, promoting basic sanitation practices. At the heart of this initiative was the thorough use of qualitative research techniques.  In their study, Ciglenecki and colleagues relied on snowball sampling methodologies to find community leaders before implementing a campaign. Snowball sampling is a qualitative research technique that relies on referrals to locate relevant stakeholders. Understanding the needs and concerns of stakeholders allows health promoters to align their objectives with those of the target populations.
Secondly, there is an urgent need for OCV funding. As described by Ciglenecki et al., the single greatest predictor of program participation is the cost of the treatment. A difference of one or two dollars can have a major impact on local participation.  OCVs present a unique challenge for donor organizations. Since cholera is characterized by a rapid onset and swift progression, it is essential to have a stockpile of vaccines for the timely implementation of mass campaigns.  International donor organizations must have sufficient resources to generate these vaccines. In the literature, the most viable approach to reducing the cost of remediation is developing a single-dose vaccine. At present, the WHO is working on developing a single-dose oral cholera vaccine. In practice, this could reduce the treatment costs by more than half, in addition to operating and administration costs. Though, further research is needed to explore this option.
Finally, this paper recommends that OCV campaigns be implemented to serve a capacity building function in cholera-endemic regions. The literature overwhelmingly agrees that mass OCV campaigns have the potential to link knowledge with practice. Vaccination campaigns are excellent tools for educating, raising awareness, and building capacity among local populations because they serve to aggregate the population in times of crisis. In developing countries, this is critical for remediation. It enables health care providers to distribute essentials resources like water and food, and it also allows them to train and educate the population on basic sanitation. An effective OCV campaign must combine the traditional approach to cholera remediation, which includes the distribution of clean water resources, hand sanitizers, antiseptics and other sanitation infrastructures, with the administration of preventative vaccines and capacity building programs.
The 2010 Haitian cholera epidemic exposed major weaknesses in the traditional approach to cholera remediation. As a consequence, the international community set out to find a viable remediation treatment for endemic cholera infection. Today, the WHO recommends that oral cholera vaccinations be administered to control cholera infection in conjunction with traditional interventions.
OCVs are newly developed vaccines and there remains considerable debate about their feasibility in mass campaigns. recent implementations of mass OCV campaigns exhibited tremendous success in controlling the spread of cholera infection. More work needs to be done to access the feasibility of implementing mass OCV campaigns in cholera-endemic regions of the world. Future efforts will necessitate the application of qualitative research methods to develop fuller understandings of contextual constraints and researchers will require support to develop more cost-effective, single-dose vaccines.
1. Aibana O, Franke MF, Teng JE, Hilaire J, Raymond M, Ivers LC. Cholera campaign contributes to improved knowledge regarding cholera and improved practice relevant to waterborne disease in rural Haiti. PLoS Negl Trop Dis. 2013; 7: e2576.
2. Merten, S, Schaetti C, Manianga C, Lapika B, Chaignat CL, Hutubessy R, Weiss MG. Local Perceptions of cholera and anticipated vaccine acceptance in katanga province, Democratic Republic of Congo. BMC Public Health. 2013; 13: 52-60.
3. World Health Organization. Cholera, 2011. Weekly Epidemiology 2012; 289–304.
4. Kar SK, Sah B, Patnaik B, Kim YH, Kerketta AS, Shin S, Rath SB, Ali M, Mogasale V, Khuntia HK, et al. Mass vaccination with a new, less expensive oral cholera vaccine using public health infrastructure in India: the Odisha model. PLoS Negl Trop Dis. 2014; 8: e2629.
5. Ministère de la Santé Publique et de la Population: Haiti 2013 MSPP daily reports on the progress of cholera in Haiti. 2013. Accessed 01 April 2014. http://www.mspp.gouv.ht/site/index.php.
6. Ciglenecki I, Sakoba K, Luquero F, Heile M, Grais R, Verhoustraeten F, Legros D. Feasibility of Mass Vaccination Campaign with Oral Cholera Vaccines in Response to an Outbreak in Guinea. PLoS Medicine 2013; 10: e1001512.
7. Sundaram N, Schaetti C, Chaignat CL, Hutubessy R, Nyambedha EO, Mbonga LA, Weiss MG. Socio-cultural determinants of anticipated acceptance of an oral cholera vaccine in Western Kenya. Epidemiol Infect. 2013; 141: 639-650.
8. Mazzeo J, Chierici, R. Social foundations for a communications-based public health cholera campaign in Borgne, Haiti. Human Organization. 2013; 72: 312-322.
9. Date K, Hyde T, Mintz E, Vicari A, Danovaro-Holliday MC. Considerations for oral cholera vaccine use during outbreak after earthquake in Haiti, 2010–2011. Emerging Infectious Disease. 2011; 17: 2105.
10. Cumberland S. An old enemy returns. Bull World Health Organization. 2009; 87: 85-86.
11. Anh DD, Lopez AL, Thiem VD, Grahek SL, Duong TN. Use of oral cholera vaccines in an outbreak in Vietnam: A case control study. PLoS Negl Tropical Disease. 2011; 5: e1006.
12. Calain P, Chaine JP, Johnson E, Hawley ML, O’Leary M. Can oral cholera vaccination play a role in controlling a cholera outbreak? Vaccine. 2004; 22: 2444–51.
13. De Brettes A, de Carsalade GY, Petinelli F, Benoit Cattin T, Coulaud X. Le cholera a Mayotte. Bulletin Epidemiologique Hebdomadaire. 2001; 8: 33–35.
14. Beatty ME, Jack T, Sivapalasingam S, Yao SS, Paul I. An Outbreak of Vibrio cholerae O1 infections on Ebeye Island, Republic of the Marshall Islands, associated with use of an adequately chlorinated water source. Clin Inf Dis. 2004; 38: 1–9.
15. Merten S, Schaetti C, Manianga C, Lapika B, Hutubessy R, Chaignat CL, Weiss M. Sociocultural determinants of anticipated vaccine acceptance for acute watery diarrhea in early childhood in Katanga Province, Democratic Republic of Congo. The American Journal of Tropical Medicine and Hygiene. 2014; 83: 419-425.
16. Beau De Rochars VE, Tipret J, Patrick M, Jacobson L, Barbour KE. Knowledge, attitudes, and practices related to treatment and prevention of cholera, Haiti, 2010. Emerging Infectious Disease. 2011; 17(11): 2158–2161.
17. Smith, Jennie M: When the Hands are Many: Community Organization and Social Change in Rural Haiti. Ithaca, N.Y.: Cornell University Press. 2001.
18. Schuller, Mark: Killing with kindness: Haiti, international aid, and NGOs. New Brunswick, N.J.: Rutgers University Press. 2012.