Effectiveness of oral cholera vaccine in Haiti
Authors: Francisco J Luquero, David A Sack
Journal: The Lancet Global Health (2015)

Although killed, whole-cell oral cholera vaccines (OCVs) have been known to be efficacious since 1986,1Clemens JD Sack DA Harris JR et al.Field trial of oral cholera vaccines in Bangladesh.Lancet. 1986; 2: 124-127Summary PubMed Scopus (251) Google Scholar and the bivalent whole-cell vaccine Shanchol has been licensed in India since 2009,2Martin S Lopez AL Bellos A et al.Post-licensure deployment of oral cholera vaccines: a systematic review.Bull World Health Organ. 2014; 92: 881-893Crossref PubMed Scopus (53) Google Scholar OCV was not regarded as useful for controlling cholera outbreaks until recently.2Martin S Lopez AL Bellos A et al.Post-licensure deployment of oral cholera vaccines: a systematic review.Bull World Health Organ. 2014; 92: 881-893Crossref PubMed Scopus (53) Google Scholar Many public health officials questioned the use of OCV,3Chaignat CL What about cholera vaccines?.Expert Rev Vaccines. 2008; 7: 403-405Crossref PubMed Scopus (13) Google Scholar including concerns about its cost, the feasibility of undertaking large campaigns, the acceptability of OCV among vaccinated communities, and the possibility of diverting resources from other interventions. There was also uncertainty as to whether the vaccine, although known to be effective in endemic countries (eg, India or Bangladesh), would be effective in areas without a history of cholera, such as Haiti. When the cholera epidemic started in Haiti, Shanchol was not yet prequalified by WHO, and only a limited supply was available, so vaccination of large numbers of people was not realistic. Assuming effectiveness in Haiti, and if the vaccine had been available and had been used earlier, computer models suggest it could have averted many cases and deaths.4Sack DA How many cholera deaths can be averted in Haiti?.Lancet. 2011; 377: 1214-1216Summary Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 5Chao DL Halloran ME Longini Jr, IM Vaccination strategies for epidemic cholera in Haiti with implications for the developing world.Proc Natl Acad Sci USA. 2011; 108: 7081-7085Crossref PubMed Scopus (118) Google Scholar, 6Andrews JR Basu S Transmission dynamics and control of cholera in Haiti: an epidemic model.Lancet. 2011; 377: 1248-1255Summary Full Text Full Text PDF PubMed Scopus (143) Google ScholarAlthough cholera vaccine was not used in the first two main waves of the epidemic, pilot projects were done in 2012 to deliver Shanchol to about 100 000 people in urban and rural Haiti.7Ivers LC Teng JE Lascher J et al.Use of oral cholera vaccine in Haiti: a rural demonstration project.Am J Trop Med Hyg. 2013; 89: 617-624Crossref PubMed Scopus (64) Google Scholar, 8Rouzier V Severe K Juste MA et al.Cholera vaccination in urban Haiti.Am J Trop Med Hyg. 2013; 89: 671-681Crossref PubMed Scopus (46) Google Scholar Subsequently, the Ministry of Health undertook larger campaigns in 2013, and plan to implement additional OCV campaigns in the coming years. Furthermore, the Ministry of Health has included the use of OCV in its national strategy for elimination of cholera, along with a continuing effort to improve water and sanitation. The earlier reports7Ivers LC Teng JE Lascher J et al.Use of oral cholera vaccine in Haiti: a rural demonstration project.Am J Trop Med Hyg. 2013; 89: 617-624Crossref PubMed Scopus (64) Google Scholar, 8Rouzier V Severe K Juste MA et al.Cholera vaccination in urban Haiti.Am J Trop Med Hyg. 2013; 89: 671-681Crossref PubMed Scopus (46) Google Scholar showed that OCV was acceptable and that OCV campaigns were feasible in Haiti, but a new report by Louise Ivers and colleagues9Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar in The Lancet Global Health provides important new information, showing that the vaccine's effectiveness in Haiti is comparable to that found in endemic countries of Asia and Africa.10Luquero FJ Grout L Ciglenecki I et al.Use of Vibrio cholerae vaccine in an outbreak in Guinea.N Engl J Med. 2014; 370: 2111-2120Crossref PubMed Scopus (117) Google Scholar Of 47 people with cholera, 33 (70%) self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8–85). Conversely, there was no association between self-reported or verified vaccination and non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI −208 to 78 by self-report and −21%, −238 to 57 by verified vaccination).Similar efficacy and effectiveness of the two killed OCVs—Dukoral and Shanchol—has been documented. The two vaccines differ in that Dukoral is more expensive and is administered in a glass of buffer solution to preserve the B subunit component of the vaccine, which increases the logistic requirements for its use. By contrast, Shanchol, which has no B subunit, needs no buffer, is less costly, and consists of only 1·5 mL liquid, which can be consumed directly from a vial. Shanchol is now available through the OCV stockpile, which is supported partly by the Global Alliance for Vaccines and Immunization. It is being used primarily as a response to an outbreak, but it will probably also be used for groups at risk in endemic areas. Clearly, much work is needed to identify how best to use the vaccine in a manner that maximises its cost-effectiveness.11Troeger C Sack DA Chao DL Evaluation of targeted mass cholera vaccination strategies in Bangladesh: a demonstration of a new cost-effectiveness calculator.Am J Trop Med Hyg. 2014; 91: 1181-1189Crossref PubMed Scopus (20) Google ScholarSome of the limitations of this study are related to the small sample size, which is a common problem in cholera effectiveness studies and which limits the ability to discern differences among subgroups. In this study, the point estimates differed in some subgroup comparisons (eg, age group and time since vaccine administration), but the sample was not powered to identify whether these differences were real. Ivers and colleagues9Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar were also not able to assess the potential for herd protection, which was found in other studies.12Ali M Emch M von Seidlein L et al.Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis.Lancet. 2005; 366: 44-49Summary Full Text Full Text PDF PubMed Scopus (252) Google Scholar, 13Ali M Sur D You YA et al.Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India.Clin Infect Dis. 2013; 56: 1123-1131Crossref PubMed Scopus (54) Google Scholar Although OCV protects vaccinated individuals, it also lowers the risk for unvaccinated neighbours if vaccine coverage is sufficiently high. Modelling work predicted that 50% coverage could avoid transmission in endemic areas.14Longini Jr, IM Nizam A Ali M Yunus M Shenvi N Clemens JD Controlling endemic cholera with oral vaccines.PLoS Med. 2007; 4: e336Crossref PubMed Scopus (152) Google Scholar Thus, further studies are needed to better understand how to maximise the effect of herd protection.Because the vaccine is in short supply and because providing two doses is logistically more complex and costly than providing only one dose, there is interest in the use of a single dose, which allows vaccination for twice as many people with the same amount of vaccine. Studies are underway to assess the efficacy of a single dose and to compare the cost-effectiveness of a single-dose versus a two-dose regimen. Even if a single dose yields a lower level of effectiveness, it may still prevent more cases in a population than a two-dose strategy because the target population can be expanded, especially in outbreak settings. The field effectiveness of and the situations in which a single-dose strategy is appropriate still need to be identified.Some additional constraints of the vaccine should be mentioned. The vaccine is registered to be kept cold, but the cold chain requirement adds to the logistics and cost of the campaign. The main antigen of Shanchol is a lipopolysaccharide, which is thermostable; hence, Shanchol has a vaccine vial monitor (VVM) category 14 (ie, if the vaccine is kept at 37°C, the colour endpoint at which discarding the vaccine is advised will be reached after 14 days). Extension to VVM category 30 would improve flexibility and reduce costs for campaigns.Following previous practice, Ivers and colleagues9Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar excluded pregnant women. Unfortunately, there is no coherence between the position of WHO, which recommends OCV for pregnant women because of their increased risk of complications and death when infected by cholera, and the package inserts, which stress the scarcity of safety data during pregnancy. Shanchol is a killed oral vaccine and is therefore expected to be safe, but additional data are needed to reassure regulators with regard to use during pregnancy.Finally, will OCV eliminate cholera from Haiti? By itself, this seems unlikely, but when combined with improved water and sanitation, health education, and high-quality treatment, OCV can play a major part in reducing this infection to low levels and quicker than if OCV is not included in the plan.The findings in this Article confirm that Shanchol is effective to protect individuals against cholera in endemic, epidemic, and intermediate contexts, and it complements previous work done by this group, which proved that OCV campaigns are feasible, well accepted, and can help to improve hygiene, water, and sanitation practices in vaccinated communities if they are well organised.15Aibana O Franke MF Teng JE Hilaire J Raymond M Ivers LC Cholera vaccination campaign contributes to improved knowledge regarding cholera and improved practice relevant to waterborne disease in rural Haiti.PLoS Negl Trop Dis. 2013; 7: e2576Crossref PubMed Scopus (25) Google Scholar These research studies should serve to reassure and help the Ministry of Health of Haiti and ministries of health of other countries to make the most effective and efficient use of OCV, with the aim of eliminating cholera.DAS is the principal investigator of the Delivering Oral Cholera Vaccine Effectively (DOVE) project. The DOVE project provided financial support to undertake the effectiveness study in Haiti. FJL declares no competing interests. Although killed, whole-cell oral cholera vaccines (OCVs) have been known to be efficacious since 1986,1Clemens JD Sack DA Harris JR et al.Field trial of oral cholera vaccines in Bangladesh.Lancet. 1986; 2: 124-127Summary PubMed Scopus (251) Google Scholar and the bivalent whole-cell vaccine Shanchol has been licensed in India since 2009,2Martin S Lopez AL Bellos A et al.Post-licensure deployment of oral cholera vaccines: a systematic review.Bull World Health Organ. 2014; 92: 881-893Crossref PubMed Scopus (53) Google Scholar OCV was not regarded as useful for controlling cholera outbreaks until recently.2Martin S Lopez AL Bellos A et al.Post-licensure deployment of oral cholera vaccines: a systematic review.Bull World Health Organ. 2014; 92: 881-893Crossref PubMed Scopus (53) Google Scholar Many public health officials questioned the use of OCV,3Chaignat CL What about cholera vaccines?.Expert Rev Vaccines. 2008; 7: 403-405Crossref PubMed Scopus (13) Google Scholar including concerns about its cost, the feasibility of undertaking large campaigns, the acceptability of OCV among vaccinated communities, and the possibility of diverting resources from other interventions. There was also uncertainty as to whether the vaccine, although known to be effective in endemic countries (eg, India or Bangladesh), would be effective in areas without a history of cholera, such as Haiti. When the cholera epidemic started in Haiti, Shanchol was not yet prequalified by WHO, and only a limited supply was available, so vaccination of large numbers of people was not realistic. Assuming effectiveness in Haiti, and if the vaccine had been available and had been used earlier, computer models suggest it could have averted many cases and deaths.4Sack DA How many cholera deaths can be averted in Haiti?.Lancet. 2011; 377: 1214-1216Summary Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 5Chao DL Halloran ME Longini Jr, IM Vaccination strategies for epidemic cholera in Haiti with implications for the developing world.Proc Natl Acad Sci USA. 2011; 108: 7081-7085Crossref PubMed Scopus (118) Google Scholar, 6Andrews JR Basu S Transmission dynamics and control of cholera in Haiti: an epidemic model.Lancet. 2011; 377: 1248-1255Summary Full Text Full Text PDF PubMed Scopus (143) Google Scholar Although cholera vaccine was not used in the first two main waves of the epidemic, pilot projects were done in 2012 to deliver Shanchol to about 100 000 people in urban and rural Haiti.7Ivers LC Teng JE Lascher J et al.Use of oral cholera vaccine in Haiti: a rural demonstration project.Am J Trop Med Hyg. 2013; 89: 617-624Crossref PubMed Scopus (64) Google Scholar, 8Rouzier V Severe K Juste MA et al.Cholera vaccination in urban Haiti.Am J Trop Med Hyg. 2013; 89: 671-681Crossref PubMed Scopus (46) Google Scholar Subsequently, the Ministry of Health undertook larger campaigns in 2013, and plan to implement additional OCV campaigns in the coming years. Furthermore, the Ministry of Health has included the use of OCV in its national strategy for elimination of cholera, along with a continuing effort to improve water and sanitation. The earlier reports7Ivers LC Teng JE Lascher J et al.Use of oral cholera vaccine in Haiti: a rural demonstration project.Am J Trop Med Hyg. 2013; 89: 617-624Crossref PubMed Scopus (64) Google Scholar, 8Rouzier V Severe K Juste MA et al.Cholera vaccination in urban Haiti.Am J Trop Med Hyg. 2013; 89: 671-681Crossref PubMed Scopus (46) Google Scholar showed that OCV was acceptable and that OCV campaigns were feasible in Haiti, but a new report by Louise Ivers and colleagues9Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar in The Lancet Global Health provides important new information, showing that the vaccine's effectiveness in Haiti is comparable to that found in endemic countries of Asia and Africa.10Luquero FJ Grout L Ciglenecki I et al.Use of Vibrio cholerae vaccine in an outbreak in Guinea.N Engl J Med. 2014; 370: 2111-2120Crossref PubMed Scopus (117) Google Scholar Of 47 people with cholera, 33 (70%) self-reported vaccination versus 167 (89%) of 188 controls (vaccine effectiveness 63%, 95% CI 8–85). Conversely, there was no association between self-reported or verified vaccination and non-cholera diarrhoea (vaccine effectiveness 18%, 95% CI −208 to 78 by self-report and −21%, −238 to 57 by verified vaccination). Similar efficacy and effectiveness of the two killed OCVs—Dukoral and Shanchol—has been documented. The two vaccines differ in that Dukoral is more expensive and is administered in a glass of buffer solution to preserve the B subunit component of the vaccine, which increases the logistic requirements for its use. By contrast, Shanchol, which has no B subunit, needs no buffer, is less costly, and consists of only 1·5 mL liquid, which can be consumed directly from a vial. Shanchol is now available through the OCV stockpile, which is supported partly by the Global Alliance for Vaccines and Immunization. It is being used primarily as a response to an outbreak, but it will probably also be used for groups at risk in endemic areas. Clearly, much work is needed to identify how best to use the vaccine in a manner that maximises its cost-effectiveness.11Troeger C Sack DA Chao DL Evaluation of targeted mass cholera vaccination strategies in Bangladesh: a demonstration of a new cost-effectiveness calculator.Am J Trop Med Hyg. 2014; 91: 1181-1189Crossref PubMed Scopus (20) Google Scholar Some of the limitations of this study are related to the small sample size, which is a common problem in cholera effectiveness studies and which limits the ability to discern differences among subgroups. In this study, the point estimates differed in some subgroup comparisons (eg, age group and time since vaccine administration), but the sample was not powered to identify whether these differences were real. Ivers and colleagues9Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar were also not able to assess the potential for herd protection, which was found in other studies.12Ali M Emch M von Seidlein L et al.Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis.Lancet. 2005; 366: 44-49Summary Full Text Full Text PDF PubMed Scopus (252) Google Scholar, 13Ali M Sur D You YA et al.Herd protection by a bivalent killed whole-cell oral cholera vaccine in the slums of Kolkata, India.Clin Infect Dis. 2013; 56: 1123-1131Crossref PubMed Scopus (54) Google Scholar Although OCV protects vaccinated individuals, it also lowers the risk for unvaccinated neighbours if vaccine coverage is sufficiently high. Modelling work predicted that 50% coverage could avoid transmission in endemic areas.14Longini Jr, IM Nizam A Ali M Yunus M Shenvi N Clemens JD Controlling endemic cholera with oral vaccines.PLoS Med. 2007; 4: e336Crossref PubMed Scopus (152) Google Scholar Thus, further studies are needed to better understand how to maximise the effect of herd protection. Because the vaccine is in short supply and because providing two doses is logistically more complex and costly than providing only one dose, there is interest in the use of a single dose, which allows vaccination for twice as many people with the same amount of vaccine. Studies are underway to assess the efficacy of a single dose and to compare the cost-effectiveness of a single-dose versus a two-dose regimen. Even if a single dose yields a lower level of effectiveness, it may still prevent more cases in a population than a two-dose strategy because the target population can be expanded, especially in outbreak settings. The field effectiveness of and the situations in which a single-dose strategy is appropriate still need to be identified. Some additional constraints of the vaccine should be mentioned. The vaccine is registered to be kept cold, but the cold chain requirement adds to the logistics and cost of the campaign. The main antigen of Shanchol is a lipopolysaccharide, which is thermostable; hence, Shanchol has a vaccine vial monitor (VVM) category 14 (ie, if the vaccine is kept at 37°C, the colour endpoint at which discarding the vaccine is advised will be reached after 14 days). Extension to VVM category 30 would improve flexibility and reduce costs for campaigns. Following previous practice, Ivers and colleagues9Ivers LC Hilaire IJ Teng JE et al.Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysis.Lancet Glob Health. 2015; 3: e162-e168Summary Full Text Full Text PDF PubMed Scopus (59) Google Scholar excluded pregnant women. Unfortunately, there is no coherence between the position of WHO, which recommends OCV for pregnant women because of their increased risk of complications and death when infected by cholera, and the package inserts, which stress the scarcity of safety data during pregnancy. Shanchol is a killed oral vaccine and is therefore expected to be safe, but additional data are needed to reassure regulators with regard to use during pregnancy. Finally, will OCV eliminate cholera from Haiti? By itself, this seems unlikely, but when combined with improved water and sanitation, health education, and high-quality treatment, OCV can play a major part in reducing this infection to low levels and quicker than if OCV is not included in the plan. The findings in this Article confirm that Shanchol is effective to protect individuals against cholera in endemic, epidemic, and intermediate contexts, and it complements previous work done by this group, which proved that OCV campaigns are feasible, well accepted, and can help to improve hygiene, water, and sanitation practices in vaccinated communities if they are well organised.15Aibana O Franke MF Teng JE Hilaire J Raymond M Ivers LC Cholera vaccination campaign contributes to improved knowledge regarding cholera and improved practice relevant to waterborne disease in rural Haiti.PLoS Negl Trop Dis. 2013; 7: e2576Crossref PubMed Scopus (25) Google Scholar These research studies should serve to reassure and help the Ministry of Health of Haiti and ministries of health of other countries to make the most effective and efficient use of OCV, with the aim of eliminating cholera. DAS is the principal investigator of the Delivering Oral Cholera Vaccine Effectively (DOVE) project. The DOVE project provided financial support to undertake the effectiveness study in Haiti. FJL declares no competing interests. Effectiveness of reactive oral cholera vaccination in rural Haiti: a case-control study and bias-indicator analysisBivalent whole-cell oral cholera vaccine effectively protected against cholera in Haiti from 4 months to 24 months after vaccination. Vaccination is an important component of efforts to control cholera epidemics. Full-Text PDF Open Access