Friday 2 July 2021 - Updated on Wednesday 26 October 2022
Learn about Epicentre's ongoing cholera studies.

Immune response to a delayed second dose of oral cholera vaccine

Manufacturers of oral cholera vaccine (OCV) recommend a 7- or 14-days interval between two doses. To carry out two rounds of mass vaccination within this delay is not always feasible and many campaigns implemented to date have used a longer interval. Recent evidence indicates that an extended interval between OCV doses might result in equivalent seroconversion rates and in an improved boosting of mucosal immune responses following the second dose. 


We aim to demonstrate the non-inferiority of the humoral immune response between individuals receiving a second Euvichol-Plus® pre-qualified OCV dose either 6 or 12 months after the initial dose and individuals receiving a second pre-qualified OCV dose 14 days after the initial dose. The humoral immune response will be assessed as the post-vaccination titer of serum vibriocidal antibodies at 14 days post-2nd dose vaccination. Secondary outcomes include the comparison of the overall rate of vibriocidal seroconversion 14 days after either the first or the second vaccine dose. A subsample of individuals ≥ 18 years will have additional serological evaluation to characterize the kinetics of their antibody responses up to 6 months after the second OCV vaccine dose. Although the vaccine is safe, occurrence of adverse events and serious adverse events following vaccination will be assessed (safety evaluation).  


The study is an open-label, randomized, controlled, non-inferiority immunogenicity trial comparing the humoral immune responses to OCV in two interventions arms (6 and 12 months interval between OCV doses) compared with a control arm (standard 14-day interval). In each arm, we aim to recruit 152 individuals aged 1 to 39 year-old eligible for OCV vaccination from the general population (ie. 456 individuals in total). 



Republic of Guinea 



Recruitment ongoing


Tentative end Date 



Our role  

Study Coordination  



MSF OCB, Ministry of Health Republic of Guinea, Massachusetts General Hospital, Grieg Foundation 

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Impact evaluations of mass oral cholera vaccination campaigns

Cholera remains a global health threat, persisting in settings with inadequate water, sanitation and hygiene (WASH) access. Killed oral cholera vaccines (OCV), in combination with WASH improvements, have become a standard component in cholera control programs. Most available evidence on OCV impact has been related to individual-level protection from clinical disease. Mass vaccination campaigns have the potential to also reduce transmission and occurrence of pandemic Vibrio cholerae in the environment. In 2020, mass OCV campaigns were deployed in cholera endemic regions of the Democratic Republic of the Congo. We are starting a 2-year study to evaluate the impacts of mass OCV roll-out in Goma and rural area of Ex-Katanga.



Our protocols combine (1) clinical surveillance, (2) serological surveys, and (3) household follow-ups. We will collaborate with health authorities to strengthen clinical surveillance systems. Culture of V. cholerae, molecular assays and cholera serology will be conducted in North Kivu (including optimisation of a qPCR assay for the simultaneous detection and differentiation of toxigenic V. cholerae O1 and O139). A sequence of serological surveys will be conducted at each study sites to assess cholera infection rates in the community, providing a measure of transmission independent of infection severity and health-seeking behaviour. Finally, a series of follow-up visits to the households of confirmed cholera cases will be conducted estimate household secondary attack rates and cholera shedding time among vaccinated and non-vaccinated persons. Environmental samples will be collected from households and water sources to monitor changes in V. cholerae detection frequency. Clinical, household, and environmental isolates will be sequenced to better understand V. cholerae circulation within households and study sites.



The study is expected to generate evidence on the long-term epidemiological and environmental impacts of mass OCV administration. The combination of clinical surveillance, serological surveys, and household contacts and environmental sampling will also contribute to improving our understanding of cholera transmission dynamics in endemic settings characteristic of transmission hotspots and inform articulated WASH-OCV strategies.



Democratic Republic of the Congo

Tentative end date


Our role

Sponsor of the study. Conception, implementation, analysis, publications


Ministry of Health DRC, PNECHOL, INRB, MSF OCP

This study is funded by the Wellcome Trust, UKaid and the Foreign and Commonwealth and Development Office (FCDO). 

Logos Wellcome UKaid

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Case-Area Targeted Intervention to contain or shorten the duration of cholera outbreaks (CATI)


Globally, the risk of small-scale cholera outbreaks propagating rapidly and enlarging extensively remains substantial. As opposed to relying on mass, community-wide approaches, cholera control strategies could focus on proactively containing the first clusters. Case-area targeted interventions (CATI) are based on the premise that early cluster detection can trigger a rapid, localised response in the high-risk radius around one or several households to reduce transmission sufficiently to extinguish the outbreak or reduce its spread. Current evidence supports a high-risk spatiotemporal zone of 100 to 250 meters around case-households for 7 days.

We hypothesize that the prompt application of CATI will reduce household transmission and transmission in the wider ring. This will result in reduced incidence in the ring and reduced clustering of cases. The local focus of CATI will enable active case-finding and sustained uptake of interventions. This will result in prompt access to care for detected cases, and reduced mortality and community transmission.

We propose to evaluate the effectiveness of a CATI strategy using an observational study design during an acute cholera epidemic, with clearly-defined measures of the effectiveness of the CATI package. In addition, we intend to evaluate the feasibility, costs, and process of implementing this approach.

The CATI package delivered by MSF will incorporate key transmission-reducing interventions (including household-level water, sanitation, and hygiene measures, active case-finding, antibiotic chemoprophylaxis, and/or single-dose oral cholera vaccination (OCV)) which aim to rapidly reduce the risk of infection in the household and in the ring around the primary case household. MSF will decide on the contents of the CATI package used, the radius of intervention and the prioritization strategy used if the caseload is higher than the operational capacity, based on national policies, the local context, and operational considerations.

The study design is based on comparing the effects of CATIs that rapidly provide protection in averting later generations of cases when compared with CATIs delayed by operational constraints (delays will not be assigned nor randomized). A regression analysis will be used to model the observed incidence of enriched RDT-positive cholera as a function of the delay to intervention (in days). The delay will reflect the inverse strength of rapid response. Groups, as a function of their delays to intervention, will serve as internal controls.



DRC, Cameroun, Zimbabwe

Tentative End date

December 2021

Our Role

Study design, Coordination, Implementation, Analysis

Who's Involved



Publications à lire


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