Cholera control: one dose at a time
Authors: Louise C Ivers
Journal: The Lancet Infectious Diseases (2018)

Cholera continues to harm the most vulnerable people worldwide.1WHOCholera, 2015.Wkly Epidemiol Rec. 2016; 91: 433-440PubMed Google Scholar As an indicator of human progress, the sustained or new presence of the disease in any region is a stark reminder of how far we, as a society, have to go to reach Sustainable Development Goal 6: ensuring availability and sustainable management of water and sanitation for all.2United NationsSustainable Development Goal 6 – Sustainable Development Knowledge Platform.https://sustainabledevelopment.un.org/sdg6Google Scholar Diarrhoeal diseases are a major source of preventable morbidity and mortality, and in 2015 claimed the lives of more than 1·3 million people, of whom 499 000 were children younger than 5 years.3GBD Diarrhoeal Diseases CollaboratorsEstimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015.Lancet Infect Dis. 2017; 17: 909-948Summary Full Text Full Text PDF PubMed Scopus (663) Google Scholar As a contributor to the global burden of diarrhoeal disease, Vibrio cholerae is a particularly harsh pathogen, causing rapid onset of severe nausea, vomiting, and profuse watery diarrhoea that can lead to death within hours—even of the healthiest young adults. Whole communities can be rapidly affected in epidemics, causing both physical harm and psychological distress. The pervasive social determinant of the problem—poor or no access to safe water, sanitation, and hygiene—means that displaced people, refugee populations, and those in conflict zones are at risk of major outbreaks of the illness. Cholera also continues to occur routinely, regularly, and with great impact (although often with less media attention) in endemic countries, such as Bangladesh and now Haiti, where children and the poorest people are the most at risk of being harmed. In both epidemic and endemic circumstances, the public health role of cholera vaccination has been re-emerging with interest from policy makers over the past 8 years. In The Lancet Infectious Diseases, Firdausi Qadri and colleagues4Qadri F Ali M Lynch J et al.Efficacy of a single dose regimen of killed whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; (published online March 5.)http://dx.doi.org/10.1016/S1473-3099(18)30108-7Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar describe results of 2 years of follow-up of a large, randomised, double-blind, placebo-controlled efficacy trial of a single dose of an inactivated whole-cell oral cholera vaccine (OCV) in Bangladesh. They found that a single dose provided protection for at least 2 years when given to adults (vaccine protective efficacy against all cholera episodes 59%, 95% CI 42–71) and to children aged 5 years or older (52%, 8–75). The findings make an important contribution to cholera control around the world, and could help to take us one step closer to WHO's ambitious goal of reducing deaths from the disease by 90% by 2030.5Global Task Force on Cholera ControlEnding cholera—a global roadmap to 2030.http://www.who.int/cholera/publications/global-roadmap/en/Google Scholar Increasing practical experiences with large-scale public health use of OCV—initially including reactive vaccination campaigns in Guinea and Haiti in 2012,6Luquero FJ Grout L Ciglenecki I Sakoba K et al.Use of Vibrio cholera vaccine in an outbreak in Guinea.N Engl J Med. 2014; 370: 2111-2120Crossref PubMed Scopus (119) Google Scholar, 7Ivers LC Teng JE Raymond M 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 revitalised WHO's support of cholera-affected countries,8WHORevitalization of the Global Task Force on Cholera Control. Working Group Meeting.http://www.who.int/cholera/task_force/Revitalization/en/Date: March 18–19, 2013Google Scholar and investment by GAVI, the vaccine alliance, in a global stockpile of vaccine—have resulted in millions of doses of OCV being used each year since 2014. The vaccine has most often been given in two doses, 14 days apart, as recommended by the manufacturers.9Desai S Pezzoli L Alberti K Martin S Costa A Perea W Legros D Achievements and challenges for the use of killed oral cholera vaccines in the global stockpile era.Hum Vaccin Immunother. 2017; 13: 579-587Crossref PubMed Scopus (26) Google Scholar Yet giving a second dose of OCV on schedule can be challenging during crisis situations. Furthermore, multiple competing demands on the global stockpile mean that, at times, officials might have to decide if they should vaccinate a population without guarantee of the availability of the second tranche of doses. Qadri and colleagues' trial complements findings from other important studies on the use of a single-dose OCV, which were largely secondary analyses and shorter-term prospective observational studies.10Azman A Parker L Rumunu J et al.Effectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study.Lancet Glob Health. 2016; 4: e856-e863Summary Full Text Full Text PDF PubMed Scopus (75) Google Scholar, 11Ferrera E Chizema-Kawesha E Blake A et al.Single-dose cholera vaccine in response to an outbreak in Zambia.N Engl J Med. 2018; 378: 577-579Crossref PubMed Scopus (36) Google Scholar Together, the evidence shows that single-dose OCV campaigns can be effective both in the short term in outbreaks and for up to 2 years in endemic settings. With these data to further support decision making on who to vaccinate against cholera and when to vaccinate them, government agencies, multilateral organisations, and non-governmental organisations should continue to invest in cholera vaccines as a part of the toolkit to control and prevent the disease. However, a single dose of OCV did not protect children younger than 5 years compared with placebo (vaccine protective efficacy against all cholera episodes −13%, 95% CI −68 to 25),4Qadri F Ali M Lynch J et al.Efficacy of a single dose regimen of killed whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trial.Lancet Infect Dis. 2018; (published online March 5.)http://dx.doi.org/10.1016/S1473-3099(18)30108-7Summary Full Text Full Text PDF PubMed Scopus (47) Google Scholar consistent with the 6-month results of the same study.12Qadri 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 Other studies show some, but reduced, protection of two doses of OCV in this age group as well, which has implications for strategies on the use of OCV in highly endemic regions where young children are an important risk group.13Bi 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; 17: 1080-1088Summary Full Text Full Text PDF PubMed Scopus (95) Google Scholar Further studies are needed to determine how best to protect the youngest individuals, and to identify the ideal dosing schedule of the vaccine. Still more evidence is needed on how to integrate vaccination strategies into evidence-based water, sanitation, and hygiene interventions to interrupt diarrhoeal disease—a subject in which evidence of impact is surprisingly scarce.14Taylor DL Kahawita TM Cairncross S Ensink JH The impact of water, sanitation and hygiene interventions on cholera: a systematic review.PLoS One. 2015; 10: e0135676Crossref PubMed Scopus (119) Google Scholar What is notable about the discourse on OCV in 2018 are the burning questions not associated with whether vaccines should be used in endemic countries or whether they should be used during epidemics for cholera control, but rather how best to use them in a way that maximises effectiveness and efficiency in saving the lives of the most vulnerable people from this entirely preventable disease. I have received grants from The Bill & Melinda Gates Foundation, outside of the submitted work. Efficacy of a single-dose regimen of inactivated whole-cell oral cholera vaccine: results from 2 years of follow-up of a randomised trialA single dose of the inactivated whole-cell OCV offered protection to older children and adults that was sustained for at least 2 years. The absence of protection of young children might reflect a lesser degree of pre-existing natural immunity in this age group. Full-Text PDF Open Access