Oral cholera vaccines: exploring the farrago of evidence

Lancet Infectious Diseases
Oct 2017 Volume 17 Number 10 p1003-1098  e306-e333

Oral cholera vaccines: exploring the farrago of evidence
Suman Kanungo, Pranab Chatterjee
Open Access
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 colleagues1 updates the estimates of the 2011 Cochrane review.2 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;3 however, updated estimates have shown that making robust assertions in the absence of accurate age-specific morbidity and mortality data is difficult.4 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.5

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.6 In our experience, in-house contamination of water remains a major problem, which sometimes persists despite efficient programmatic implementation of WaSH strategies.7 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.8, 9, 10

Modelling studies have suggested that in areas with poor sanitation, isolated efforts for water quality improvement are likely to be met with low success.11 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.11 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.12 Only point-of-use interventions and safe water storage were effective measures in reducing diarrhoea incidence.12 By contrast, a single-dose regimen was an effective strategy to combat a cholera outbreak in South Sudan and an endemic focus in Bangladesh.13, 14

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.
[References at article title link]