Euvichol-S: documenting the operational effectiveness of this new oral cholera vaccine

What is the current situation with regard to cholera vaccines? 

Laure Madé: In 2023, Euvichol-plus became the only cholera vaccine available in the WHO's global stockpile after Shanchol was discontinued. It is used in mass vaccination campaigns, particularly via the global stockpile managed by the WHO and Gavi, to respond to cholera epidemics. Its effectiveness is well documented: in Zambia, two doses showed 81% effectiveness and 66% in Bangladesh, based on interim results six months after vaccination (1). 

However, the global vaccine shortage forces health authorities to administer a single dose in reactive campaigns, even though the recommended schedule calls for two. In the Democratic Republic of Congo (DRC), a single dose provided nearly 53% protection between 12 and 17 months after vaccination, but this effectiveness fell to 44.7% between 24 and 36 months. This shows the importance of monitoring the evolution of protection over time (2), and to document effectiveness of a single-dose schedule, which has become the commonplace out of necessity. In response to this situation, in 2024 the WHO prequalified Euvichol-S, a simplified version of Euvichol-Plus, designed to speed up production and meet growing demand. This vaccine is now part of the global stockpile of oral cholera vaccines. Whereas the vaccine has a proven track record in immunogenicity trials, its effectiveness in real-world conditions, particularly in epidemic settings and in a single-dose regimen, remains to be documented—which is precisely the aim of the new study.

What does Euvichol-S offer that its predecessor does not?

Dan Nyehangane: Euvichol-S is based on the same inactivated strains of Vibrio cholerae O1 (Inaba and Ogawa), but its formulation has been simplified: it contains only two components instead of five. This simplification facilitates industrial production, reduces costs, and improves global availability—a major challenge in times of high demand and shortages.

However, its prequalification by the WHO is based solely on immunogenicity data. Hence, the need for additional studies, such as ours, which aim not only to evaluate the vaccine's effectiveness in the field, but also to analyze its impact according to age, gender, and its ability to prevent severe forms of cholera.

What are the challenges for local populations? And why was South Sudan chosen for the study? 

Laure Madé: Cholera remains a major threat in many countries. South Sudan has faced regular cholera epidemics in recent years. The latest was officially declared on October 28, 2024, by the national Ministry of Health, after the first suspected cases appeared in Renk County, located in Upper Nile State. The epidemic quickly spread to other regions, including the capital, Juba. By early September 2025, the country had recorded more than 90,000 cases nationwide and 1,500 deaths.

In response to the emergency, the Ministry of Health launched a vaccination campaign in all affected areas. As of mid October, 2025, more than 8.5 million people had been vaccinated, according to the Ministry of Health.

South Sudan is also one of the countries where MSF has one of its largest operational volumes in all respects (number of patients, staff, programs, etc.).

These two aspects explain why we decided to conduct the study in South Sudan. It will take place in areas where people have been vaccinated with Euvichol-S.

What method do you use to estimate the protection offered by the cholera vaccine? 

Laure Madé: It is a matched case-control study. In concrete terms, each person with cholera (the "case") is included when they arrive at a health center. Then, five healthy people (the "controls") are matched in the community. The controls should be as similar as possible to the cases, e.g. same neighborhood, same age group and the same sex. 

For each person included in the study, whether sick or control, field teams will ask if they received the vaccine and, if available, verifies the vaccination cards. By comparing how many of the cases and how many of the controls were vaccinated, we can then estimate how good the vaccine is protecting against cholera.

How will cholera cases be confirmed?

Dan Nyehangane: The diagnosis of cholera cases will combine rapid tests, bacterial cultures, and molecular analyses. As soon as a person suspected of having cholera is admitted, a fresh stool sample is taken by trained healthcare personnel, if possible before antibiotics are administered. Two initial types of tests are performed on this sample:

• A rapid diagnostic test (RDT) on site, for initial guidance.
• A bacterial culture, performed at the National Public Health Laboratory in Juba, in accordance with the recommendations of the Global Task Force on Cholera Control (GTFCC).

But the key stage of this study relies on qPCR analyses, which will be carried out in the National Public Health laboratory in Juba with our technical support. These analyses will enable us to identify the serogroup (O1 or O139) and genetically characterize the strains in circulation and their quantity.

Why is a real-world study essential?

Laure Madé: Immunogenicity studies—such as those that led to the prequalification of Euvichol-S—demonstrate that the vaccine triggers an immune response. But to understand and guide their use in the real world in diverse settings where many factors can influence protection (sanitary conditions, age groups, geographic areas, or the virulence of local strains), we need a study directly in the community with an ongoing cholera outbreak, which is called an effectiveness study.

Added to this is a lack of data on the effectiveness of reactive campaigns – campaigns that started after a cholera outbreak has been declared - conducted with a single dose, a regimen that has become common due to shortages. This need is particularly crucial for Euvichol-S, which was recently added to the global stockpile but is still poorly documented in epidemic situations. Children under five, in whom effectiveness may be lower, are also underrepresented in the available data.

This study aims to fill these gaps to inform public health decisions in a context of high epidemic pressure and limited resources.

(1) Protection from killed whole-cell cholera vaccines: a systematic review and meta-analysis Hanmeng Xu, MPH et coll. The Lancet Global Health. Volume 13, Issue 7e1203-e1212July 2025

(2) Malembaka EB, Bugeme PM, Hutchins C, Xu H, Hulse JD, Demby MN, et al. Effectiveness of one dose of killed oral cholera vaccine in an endemic community in the Democratic Republic of the Congo: a matched case-control study. Lancet Infect Dis. 2024;24: 514–522. doi:10.1016/S1473-3099(23)00742-9