Comment
New strategies for cholera control Cholera remains a serious global public health problem, disproportionately affecting poor individuals, causing illness and death for thousands of people each year. Cholera cases are on the rise, with 47% more cases reported to WHO in 2014 than in 2013.1 Innovative approaches to control the disease are urgently needed, and the study by Andrew Azman and colleagues in The Lancet Global Health2 contributes to growing evidence of the important part that oral cholera vaccine strategies have to play in this regard. Cholera can have devastating consequences, especially in epidemic settings. Azman and colleagues’ study assesses the effectiveness of a single dose of bivalent whole-cell oral cholera vaccine on epidemic cholera in Juba, South Sudan. Typically, this oral cholera vaccine is given in two doses 14 days apart, and studies have shown its efficacy and effectiveness with this dosing schedule.3–5 However, the use of one dose of vaccine for an outbreak response would reduce costs and double the number of people that could be served, which is especially important considering the global shortage of vaccine that is expected to last for the next few years. Faced with an emerging epidemic of cholera in South Sudan, limited vaccine supply, and some evidence that a single dose of vaccine might give sufficient protection to thwart an epidemic, local public health officials and the non-governmental organisation Médecins Sans Frontières decided to proceed with a single-dose public health oral cholera vaccine campaign in Juba. Public health activities and a research study took place hand in hand. The study found that the adjusted single-dose vaccine effectiveness was 87·3% (70·2–100·0) for reducing medically attended cholera for up to 2 months. This adds to existing evidence including a randomised study of a single-dose regimen from Bangladesh that found 40% direct effectiveness for reducing all cholera, and 63% direct effectiveness for reducing severely dehydrating cholera at 6 months.6 By contrast, Azman and colleagues used a case-cohort study design in an effort to measure both the direct and indirect protection offered by the vaccine (ie, herd protection), and measured effectiveness in a shorter period. This design makes the study particularly interesting and pertinent to dilemmas in the approach to cholera outbreak control. www.thelancet.com/lancetgh Vol 4 November 2016
Debate continues between water, sanitation, and hygiene (WASH) purists, who believe that investments in cholera vaccination campaigns are a distraction from the goal of universal access to water and sanitation, and a more progressive public health community that advocates for a combined approach to cholera control including vaccination and evidence-based WASH interventions. In this context, a study that helps us to measure the herd protection of an oral cholera vaccine strategy is key to understanding the population-level effect and therefore the public health usefulness of oral cholera vaccine (beyond individual protection). This study is also an excellent example of research in action. Resolving, as the researchers did, to be scientific in the context of rapid decision making and the often chaotic environment of an epidemic response is not straightforward. The context of the study means that the results are particularly useful for understanding the intervention as it might happen in the real world, outside of a formal research setting. More studies like this are needed for us to understand the right approaches for use of cholera vaccine. Armed with the results of this study, public health officials and implementing organisations in areas where cholera occurs with some frequency should consider the option of using a single-dose vaccination campaign as part of an emergency outbreak response. This should be coupled with good monitoring and evaluation activities to continue to add to our knowledge on the issue. Importantly, the usefulness of single-dose oral cholera vaccine in cholera-naive populations cannot be presumed on the basis of this study, and the authors acknowledge this fact. The impetus now exists, though, to study the approach in cholera-naive populations. Further questions also emerge that remain to be answered. How long does the protective effect of a single dose of this oral cholera vaccine last in choleraexperienced populations such as Juba? Does a singledose pre-emptive campaign prevent epidemic outbreaks in susceptible groups such as displaced people? How well protected are subgroups such as young children? What complementary emergency WASH activities at household or community level should be combined with the single-dose approach to ensure durable control of cholera? Would a booster dose sometime after the
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Comment
initial outbreak response contribute to longer-term cholera control? To answer these pragmatic questions, we require continued investment in the global stockpile of cholera vaccine, forward-thinking health officials, and continued assessment of the vaccine’s use. When the right to universal access to safe water and sanitation is realised, the world will be a better, healthier place—this is not doubted. However, if Haiti is any example, the struggle to execute on water and sanitation ideals is real. Those challenges are related both to the availability of funding, and the ability to deliver WASH interventions in sufficient quantity and quality to interrupt transmission of cholera as a matter of urgency. While the 2016 rainy season brings a surge in cholera cases in Haiti, this study offers one potential vaccination strategy to consider in outbreak responses going forward. We can only wonder what might have happened in Haiti if Azman and colleagues’ research had pre-dated the Haitian cholera outbreak—the largest ongoing cholera outbreak in the world, with more than 10 000 deaths so far.7,8 Perhaps officials, public health experts, and vaccine manufacturers would have done
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innovative work together in the early days, and helped to avert a disaster. Louise C Ivers Harvard Medical School, Boston, MA 02115, USA
[email protected] I declare no competing interests. Copyright © The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. 1 2
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WHO. Cholera 2014. Wkly Epidemiol Rec 2015; 90: 517–44. Azman 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 Health 2016; 4: e856–63. Sinclair D, Abba K, Zaman K, Qadri F, Graves PM. Oral vaccines for preventing cholera. Cochrane Database Syst Rev 2011; 3: CD008603. Luquero FJ, Grout L, Ciglenecki I, et al. Use of Vibrio cholerae vaccine in an outbreak in Guinea. N Engl J Med 2014; 370: 2111–20. Ivers LC, Hilarie 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: e162–68. Qadri F, Wierzba TF, Ali M, et al. Efficacy of a single-dose, inactivated oral cholera vaccine in Bangladesh. N Engl J Med 2016; 374: 1723–32. Ministére Santé Publique et de la Population, Direction d’Epidémiologie de Laboratoire et de Recherches. Rapport du Réseau National de Surveillance, 27eme semain épidémiologique. 2016. http://mspp.gouv.ht/ (accessed Sept 1, 2016). Luquero FJ, Rondy M, Boncy J, et al. Mortality rates during cholera epidemic, Haiti, 2010–2011. Emerg Infect Dis 2016; 22: 410–16.
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