Oral cholera vaccines: exploring the farrago of evidence
Authors: Suman Kanungo, Pranab Chatterjee
Journal: The Lancet Infectious Diseases (2017)

The development of a cheap and effective oral cholera vaccine (OCV) is a remarkable achievement in the field of cholera prevention. A meta-analysis on the efficacy and effectiveness of OCVs by Qifang Bi and colleagues1Bi Q Ferreras E Pezzoli L et al.Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysis.Lancet Infect Dis. 2017; (published online July 17.)http://dx.doi.org/10.1016/S1473-3099(17)30359-6PubMed Google Scholar updates the estimates of the 2011 Cochrane review.2Sinclair D Abba K Zaman K Qadri F Graves PM Oral vaccines for preventing cholera.Cochrane Database Syst Rev. 2011; 3 (CD008603.)Google Scholar Their analysis includes additional studies published since 2011, yet provides estimates that are almost the same. The debate about the low efficacy of OCVs in children aged younger than 5 years has continued to dominate the policy discourse in endemic countries such as India, where children are the main target of immunisation programmes. Older estimates identified children younger than 5 years to be at a disproportionately higher risk of cholera than other age groups;3Ali M Lopez AL You YA et al.The global burden of cholera.Bull World Health Organ. 2012; 90 (18A): 209Crossref PubMed Scopus (322) Google Scholar however, updated estimates have shown that making robust assertions in the absence of accurate age-specific morbidity and mortality data is difficult.4Ali M Nelson AR Lopez AL Sack DA Updated global burden of cholera in endemic countries.PLoS Negl Trop Dis. 2015; 9: e0003832Crossref Scopus (569) Google Scholar This uncertainty has further contributed to a policy-level hesitancy in adopting OCVs for widespread use in endemic countries. Crucially, more accurate estimates of cholera burden should be established to enable programmatic implementation of OCVs, and the reasons for poor immune responses to OCVs in children need to be understood. Furthermore, we propose that the extent of herd protection offered by OCVs should be established, especially in children, if a targeted vaccination policy covering all age groups is endorsed for highly endemic hotspots.5Dimitrov DT Troeger C Halloran ME Longini IM Chao DL Comparative effectiveness of different strategies of oral cholera vaccination in Bangladesh: a modeling study.PLoS Negl Trop Dis. 2014; 8: e3343Crossref PubMed Scopus (21) Google Scholar Water, sanitation, and hygiene (WaSH) interventions are considered to be the best method of cholera control, but gaps have been shown in the knowledge about which interventions work best.6Taylor DL Kahawita TM Cairncross S Ensink JH The impact of water, sanitation and hygiene interventions to control cholera: a systematic review.PLoS One. 2015; 10: e0135676Google Scholar In our experience, in-house contamination of water remains a major problem, which sometimes persists despite efficient programmatic implementation of WaSH strategies.7Palit A Batabyal P Kanungo S Sur D In-house contamination of potable water in urban slum of Kolkata, India: a possible transmission route of diarrhea.Water Sci Technol. 2012; 66: 299-303Crossref PubMed Scopus (31) Google Scholar Trials in India have shown similar problems, and a rural sanitation programme failed to show evidence of prevention of diarrhoea and soil-transmitted helminth infections or reduction in faecal contamination of water sources.8Clasen T Boisson S Routray P et al.Effectiveness of a rural sanitation programme on diarrhoea, soil-transmitted helminth infection, and child malnutrition in Odisha, India: a cluster-randomised trial.Lancet Glob Heal. 2014; 2: e645-e653Summary Full Text Full Text PDF PubMed Scopus (333) Google Scholar, 9Odagiri M Schriewer A Daniels ME et al.Human fecal and pathogen exposure pathways in rural Indian villages and the effect of increased latrine coverage.Water Res. 2016; 100: 232-244Crossref PubMed Scopus (73) Google Scholar, 10Schriewer A Odagiri M Wuertz S et al.Human and animal fecal contamination of community water sources, stored drinking water and hands in rural India measured with validated microbial source tracking assays.Am J Trop Med Hyg. 2015; 93: 509-516Crossref PubMed Scopus (76) Google Scholar Modelling studies have suggested that in areas with poor sanitation, isolated efforts for water quality improvement are likely to be met with low success.11Eisenberg JN Scott JC Porco T Integrating disease control strategies: balancing water sanitation and hygiene interventions to reduce diarrheal disease burden.Am J Public Health. 2007; 97: 846-852Crossref PubMed Scopus (96) Google Scholar Further, considering the high endemicity of cholera in low-income and middle-income countries (LMICs), single-pathway interventions are likely to be inadequate in the control of diarrhoeal diseases, and cholera in particular because of environmental persistence of vibrios, which might not be eradicated even with stringent implementation of such interventions.11Eisenberg JN Scott JC Porco T Integrating disease control strategies: balancing water sanitation and hygiene interventions to reduce diarrheal disease burden.Am J Public Health. 2007; 97: 846-852Crossref PubMed Scopus (96) Google Scholar Besides, deploying adequate WaSH interventions takes time because it involves significant investment in infrastructural improvements and behavioural changes. Keeping these issues in mind, cheap and effective OCVs emerge as a viable option to keep cholera at bay, reducing morbidity and mortality, while the definitive WaSH interventions are identified and rolled out. The successful expansion of the Swachh Bharat (Clean India) mission in India provides a governance-driven model of sanitation and hygiene promotion that can be replicated in other LMICs; however, its effectiveness in reducing numbers of cases and deaths from cholera or diarrhoeal diseases needs to be systematically studied. Although cholera outbreaks in areas of political and civil unrest are a major concern, strategies to mitigate the risks have been poorly studied. Mortality and morbidity from cholera in complex emergencies remains high. A systematic review showed that the evidence on the effectiveness of WaSH interventions in times of humanitarian crises is scarce and of poor quality.12Ramesh A Blanchet K Ensink JH Roberts B Evidence on the effectiveness of water, sanitation, and hygiene (WASH) interventions on health outcomes in humanitarian crises: a systematic review.PLoS One. 2015; 10: e0124688Crossref Scopus (64) Google Scholar Only point-of-use interventions and safe water storage were effective measures in reducing diarrhoea incidence.12Ramesh A Blanchet K Ensink JH Roberts B Evidence on the effectiveness of water, sanitation, and hygiene (WASH) interventions on health outcomes in humanitarian crises: a systematic review.PLoS One. 2015; 10: e0124688Crossref Scopus (64) Google Scholar By contrast, a single-dose regimen was an effective strategy to combat a cholera outbreak in South Sudan and an endemic focus in Bangladesh.13Azman AS Parker LA Rumunu J et al.Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.Lancet Glob Heal. 2016; 4: e856-e863Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 14Qadri F Wierzba TF Ali M et al.Efficacy of a single-dose, inactivated oral cholera vaccine in Bangladesh.N Engl J Med. 2016; 374: 1723-1732Crossref PubMed Scopus (110) Google Scholar The creation of an OCV stockpile, and the commitment of Gavi, the Vaccine Alliance, to support vaccination of emergency and endemic areas of cholera activity, provides a cost-effective method by which countries can access vaccines as they work towards universal deployment of adequate WaSH facilities. In our opinion, a balanced public health policy needs to be in place, in which OCVs are used as a synergistic tool for cholera control, while the most efficient, cost-effective, and locally feasible, acceptable, and relevant WaSH interventions are identified and deployed. Given that even in endemic countries, cholera is a public health menace only in specific regions, with multiple local factors contributing to disease epidemiology, health policies need to be customised to fit the local contexts, eschewing one-size-fits all approaches. We declare no competing interests. Protection against cholera from killed whole-cell oral cholera vaccines: a systematic review and meta-analysisTwo kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control. Full-Text PDF Open Access