The scenario approach for countries considering the addition of oral cholera vaccination in cholera preparedness and control plans

doi:10.1016/S1473-3099(15)00298-4

The Lancet Infectious Diseases

Volume 16, Issue 1, January 2016, Pages 125-129

https://doi.org/10.1016/S1473-3099(15)00298-4 Get rights and content

Summary

Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. The supply of licensed, WHO-prequalified cholera vaccines is not sufficient to meet endemic and epidemic needs worldwide and so prioritisation is needed. We have developed a scenario approach to systematically classify situations in which oral cholera vaccination might be useful. Our scenario approach distinguishes between five types of cholera epidemiology based on experiences from around the world and provides evidence that we hope will spur the development of detailed guidelines on how and where oral cholera vaccines could, and should, be most rationally deployed.

Introduction

Responding to cholera outbreaks is challenging, since these life-threatening events can spread rapidly through populations and often occur in areas with the least health resources and poorest water and sanitation infrastructure. In parallel with timely treatment, access to potable water, food hygiene, adequate sanitation, and community engagement, WHO recommends that oral cholera vaccination be considered in areas where the disease is endemic (with seasonal peaks), as part of the response to outbreaks, or in a humanitarian crisis during which the risk of cholera is high,¹ but the global supply of the vaccine is small compared with the population at risk for cholera.

Two internationally available and WHO-prequalified oral cholera vaccines are on the market.² The first is an inactivated vaccine containing killed whole cells of Vibrio cholerae O1 with recombinant B subunit of cholera toxin marketed as Dukoral (Valneva, Sweden), which was prequalified in 2001. The second, prequalified in 2011, is a bivalent inactivated vaccine containing killed whole-cells of V cholerae O1 and V cholerae O139 and marketed as Shanchol (Shantha Biotechnics, Sanofi). Both Dukoral and Shanchol are given in two doses and confer direct and indirect (herd) immunity. Dukoral may be given to individuals aged 2 years and older and is taken with a bicarbonate buffer. Shanchol may be given to those aged 1 year and older, does not require a buffer, is less complicated to deliver, and is cheaper than Dukoral.²

Shanchol is available through a WHO oral cholera vaccine stockpile, which was created in 2012.3, 4 Currently, nearly all available Shanchol doses are in the stockpile and reserved for use in outbreaks or complex emergencies. There is increasing experience on oral cholera vaccine deployment,⁵ but no consensus exists on where and when to use the limited doses available in the best way. Cholera epidemiology varies greatly by region, affecting different age groups and different populations during varying time periods. Considering the oral cholera vaccine shortage, funding scarcity, and the presence of competing vaccination priorities, specific recommendations about when to consider oral cholera vaccines would be useful. A WHO decision-making tool is available that helps practitioners decide when oral cholera vaccines should be used in complex emergency situations, during cholera outbreaks, and in endemic settings,6, 7 but it does not provide specific recommendations.

The absence of detailed guidelines is understandable considering the difficulty of predicting cholera outbreaks and the challenges of implementing mass vaccinations in many areas where the disease occurs. We have developed a scenario approach that systematically classifies situations in which oral cholera vaccination might be useful. Our scenario approach distinguishes between five types of cholera epidemiology based on experiences from around the world. Each scenario, with examples, is described, followed by our recommendation for oral cholera vaccination. The scenarios and recommendations are summarised in the table. More than one scenario can describe a particular area and a scenario can evolve into another over time. This approach is by no means final, but we hope that it can start to build consensus on how and where oral cholera vaccination would be most useful.

Section snippets

Five cholera scenarios and recommendation for oral cholera vaccine use

When using the scenario approach, we need as much information as is available from the affected area about cholera cases, cholera deaths, diarrhoeal disease management, population displacement, access to treatment, water and sanitation problems, and the capacity to solve these problems. The minimum requirements for accessing vaccine from the stockpile include reporting of a culture-confirmed cholera outbreak, submission of a completed request form and accompanying annexes, submission of a

Discussion

The availability of an affordable cholera vaccine and the creation of a vaccine stockpile have generated an opportunity for wider use of oral cholera vaccination. We propose here an approach that decision makers can use in different cholera situations. With additional experience in using this method, the scenario approach can be further revised and fine-tuned. Revision will be particularly relevant for some of the terms used to describe the different scenarios, which might be thought of as

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Cited by (12)

Global oral cholera vaccine use, 2013–2018
2020, Vaccine
Citation Excerpt :
In 2013, WHO, with funding (i.e. vaccine costs and since 2016 operational costs for campaign implementation) from GAVI, the Vaccine Alliance, created an OCV stockpile to respond to emergency situations [14], including outbreaks and humanitarian crises [15–17]. The OCV stockpile is also used in non-emergency settings as one of the key strategies to contribute controlling cholera in endemic areas (i.e. “cholera hotspots”), [18,19]. Ideally, OCV should be used in conjunction with other preventative measures such as WASH interventions and social mobilization.
Vaccination is a key intervention to prevent and control cholera in conjunction with water, sanitation and hygiene activities. An oral cholera vaccine (OCV) stockpile was established by the World Health Organization (WHO) in 2013. We reviewed its use from July 2013 to all of 2018 in order to assess its role in cholera control. We computed information related to OCV deployments and campaigns conducted including setting, target population, timelines, delivery strategy, reported adverse events, coverage achieved, and costs.
In 2013–2018, a total of 83,509,941 OCV doses have been requested by 24 countries, of which 55,409,160 were approved and 36,066,010 eventually shipped in 83 deployments, resulting in 104 vaccination campaigns in 22 countries. OCVs had in general high uptake (mean administrative coverage 1st dose campaign at 90.3%; 2nd dose campaign at 88.2%; mean survey-estimated two-dose coverage at 69.9%, at least one dose at 84.6%) No serious adverse events were reported. Campaigns were organized quickly (five days median duration). In emergency settings, the longest delay was from the occurrence of the emergency to requesting OCV (median: 26 days). The mean cost of administering one dose of vaccine was 2.98 USD.
The OCV stockpile is an important public health resource. OCVs were generally well accepted by the population and their use demonstrated to be safe and feasible in all settings. OCV was an inexpensive intervention, although timing was a limiting factor for emergency use. The dynamic created by the establishment of the OCV stockpile has played a role in the increased use of the vaccine by setting in motion a virtuous cycle by which better monitoring and evaluation leads to better campaign organization, better cholera control, and more requests being generated. Further work is needed to improve timeliness of response and contextualize strategies for OCV delivery in the various settings.
Model distinguishability and inference robustness in mechanisms of cholera transmission and loss of immunity
2017, Journal of Theoretical Biology
Citation Excerpt :
Estimates of the length of immunity in the literature range widely from several months to three to ten years (Levine et al., 1981; King et al., 2008; Koelle and Pascual, 2004). Immunity to cholera is of particular interest given the recent and ongoing oral cholera vaccine campaigns worldwide, including in Haiti, Bangladesh, and Thailand (Tohme et al., 2015; O'Leary and Mulholland, 2015; Deen et al., 2016; Phares et al., 2016), which raise additional questions of how vaccine-derived immunity compares to immunity derived from infection. As modeling gains prevalence among policy makers in public health (Abrams et al., 2012; Moyer, 2014; Auchincloss and Roux, 2008; Grad et al., 2012; Lofgren et al., 2014; Lipsitch et al., 2011), comparative or ensemble modeling approaches have been increasingly viewed as a way to ensure that the results of parameter estimation, forecasting efforts, and the evaluation of intervention strategies are conserved across the range of realistic model structures (Koopman, 2004; Meza et al., 2014).
Mathematical models of cholera and waterborne disease vary widely in their structures, in terms of transmission pathways, loss of immunity, and a range of other features. These differences can affect model dynamics, with different models potentially yielding different predictions and parameter estimates from the same data. Given the increasing use of mathematical models to inform public health decision-making, it is important to assess model distinguishability (whether models can be distinguished based on fit to data) and inference robustness (whether inferences from the model are robust to realistic variations in model structure).
In this paper, we examined the effects of uncertainty in model structure in the context of epidemic cholera, testing a range of models with differences in transmission and loss of immunity structure, based on known features of cholera epidemiology. We fit these models to simulated epidemic and long-term data, as well as data from the 2006 Angola epidemic. We evaluated model distinguishability based on fit to data, and whether the parameter values, model behavior, and forecasting ability can accurately be inferred from incidence data.
In general, all models were able to successfully fit to all data sets, both real and simulated, regardless of whether the model generating the simulated data matched the fitted model. However, in the long-term data, the best model fits were achieved when the loss of immunity structures matched those of the model that simulated the data. Two parameters, one representing person-to-person transmission and the other representing the reporting rate, were accurately estimated across all models, while the remaining parameters showed broad variation across the different models and data sets. The basic reproduction number ( $R_{0}$ ) was often poorly estimated even using the correct model, due to practical unidentifiability issues in the waterborne transmission pathway which were consistent across all models. Forecasting efforts using noisy data were not successful early in the outbreaks, but once the epidemic peak had been achieved, most models were able to capture the downward incidence trajectory with similar accuracy. Forecasting from noise-free data was generally successful for all outbreak stages using any model.
Our results suggest that we are unlikely to be able to infer mechanistic details from epidemic case data alone, underscoring the need for broader data collection, such as immunity/serology status, pathogen dose response curves, and environmental pathogen data. Nonetheless, with sufficient data, conclusions from forecasting and some parameter estimates were robust to variations in the model structure, and comparative modeling can help to determine how realistic variations in model structure may affect the conclusions drawn from models and data.
The corn smut-made cholera oral vaccine is thermostable and induces long-lasting immunity in mouse
2016, Journal of Biotechnology
Citation Excerpt :
The emergence of large and prolonged outbreaks, particularly in sub-Saharan Africa, make WHO to reconsider the recommendation of not oral cholera vaccination once an outbreak had started (Bhattacharya et al., 2009). Therefore, the limited economic resources in the affected countries limit the current supply of cholera vaccines to implement national vaccination campaigns and are not sufficient to meet endemic and epidemic worldwide needs (Deen et al., 2015). Thus, the development of the research and development of new affordable vaccines is crucial to prevent cholera outbreaks.
The use of corn smut for the production of recombinant vaccines has been recently implemented by our group. In this study, the stability and immunogenic properties of the corn smut-based cholera vaccine, based on the cholera toxin B subunit (CTB), were determined in mouse. The immunogenic potential of distinct corn smut CTB doses ranging from 1 to 30 μg were assessed, with maximum humoral responses at both the systemic (IgG) and intestinal (IgA) levels at a dose of 15 μg. The humoral response last for up to 70 days after the third boost. Mice were fully protected against a challenge with cholera toxin after receiving three 15 μg-doses. Remarkably, the corn smut-made vaccine retained its immunogenic activity after storage at room temperature for a period of 1 year and no reduction on CTB was observed following exposure at 50 °C for 2 h. These data support the use of the corn smut-made CTB vaccine as a highly stable and effective immunogen and justify its evaluation in target animal models, such as piglet and sheep, as well as clinical evaluations in humans.
Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR
2016, Travel Medicine and Infectious Disease
Citation Excerpt :
Cholera is in many parts of the world still endemic, causing epidemics and constituting repeatedly serious public health problems [1,2], such as the recent large and long-lasting outbreaks in Zimbawe [3] and Haiti [4]. Effective and easy to administer cholera vaccines are today in need more than ever, for populations in endemic areas and for outbreak interventions [5–7], as well as for travellers and aid workers at risk [8,9]. The use of the reactogenic and relative ineffective injectable cholera vaccines was stopped in the early 1970s [10].
Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80–100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need.
A Systematic Review of Vaccination Guidance for Humanitarian Responses
2023, Vaccines
Vibrio cholerae and cholera: A recent African perspective
2020, Current Microbiological Research in Africa: Selected Applications for Sustainable Environmental Management

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Personal ViewThe scenario approach for countries considering the addition of oral cholera vaccination in cholera preparedness and control plans

Summary

Introduction

Section snippets

Five cholera scenarios and recommendation for oral cholera vaccine use

Discussion

Lancet Infect Dis

Lancet Infect Dis

Cholera, 2013

Wkly Epidemiol Rec

New-generation vaccines against cholera

Nat Rev Gastroenterol Hepatol

Stockpiling oral cholera vaccine

Bull World Health Organ

Post-licensure deployment of oral cholera vaccines: a systematic review

Bull World Health Organ

Oral cholera vaccines in mass immunization campaigns: guidance for planning and use

Guidance on how to access the oral cholera vaccine (OCV) from the ICG emergency stockpile

An old enemy returns

Bull World Health Organ

The case for reactive mass oral cholera vaccinations

PLoS Negl Trop Dis

Meeting of the Strategic Advisory Group of Experts on immunization, October 2009—conclusions and recommendations

Wkly Epidemiol Rec

Considerations for oral cholera vaccine use during outbreak after earthquake in Haiti, 2010–2011

Emerg Infect Dis

Use of oral cholera vaccine in Haiti: a rural demonstration project

Am J Trop Med Hyg

Personal View
The scenario approach for countries considering the addition of oral cholera vaccination in cholera preparedness and control plans