Clinical trials

Malnutrition and infectious disease form a vicious circle, posing a double threat to vulnerable children in low- and middle-income countries. Malnutrition makes children more vulnerable to infectious diseases, while infectious diseases increase the risk of malnutrition. When caught in this cycle, children are far more likely to die or suffer adverse effects on their health and development. High rates of wasting and low immunization coverage also constitute a weakening double burden for already fragile health systems. Every year in these contexts, hundreds of thousands of children are treated for severe wasting, while at the same time suffering repeated and prolonged epidemics of vaccine-preventable diseases such as measles. Rural areas of Chad and Niger are at the heart of this dynamic, recording some of the worst indicators of malnutrition and low vaccination coverage rates. Small-quantity lipid-based nutritional supplements (SQ-LNS) are a category of ready-to-use, nutrient-dense food supplements fortified with micronutrients, designed to prevent malnutrition and improve child survival, growth and development. A recent meta-analysis on SQ-LNS reveals that giving a child just one sachet of SQ-LNS a day for a year can reduce the risk of mortality by 27%, iron-deficiency anemia by 64%, severe wasting by 31% and severe stunting by 17%. The recent World Health Organization (WHO) guideline on complementary feeding of infants and young children aged 6 to 23 months recently recommended the use of SQ-LNS in certain contexts of food insecurity, based on evidence deemed "very safe". The distribution of SQ-LNS is also promising as an incentive for vaccination, as well as for other health services, such as participation in infant growth monitoring programs. Various operational experiences suggest that it is likely to have an impact on increasing vaccination coverage, and a modeling simulation suggests that it would lead to a significant reduction in measles morbidity and mortality. The main objective of OptiMAx is to estimate the effectiveness of a mass SQ-LNS supplementation program coupled with the routine immunization program compared with the routine immunization program alone in terms of vaccination coverage against pentavalent 1 (Niger) and measles 1 (Chad), after 12 months of program implementation, in children aged 12 to 23 months as part of an annual cross-sectional household survey. Secondary objectives include: * Estimate the effectiveness of a mass SQ-LNS supplementation program combined with the routine Essential Program on Immunization (EPI) compared with the routine EPI alone in children aged 6-18 months, after 12 months of program implementation, in terms of 1) coverage of pentavalent 3 vaccine, malaria and other childhood vaccines, 2) on-time immunization for age-eligible children. * Evaluate the feasibility and reliability of combining measles and pentavalent coverage measurements during annual MUAC-family training campaigns;. * Evaluate outcomes of acutely malnourished children who received SQ-LNS supplementation prior to RUTF treatment (as part of their inclusion in the OptiMA study) versus those who did not receive SQ-LNS supplementation The specific objectives of the process evaluation (with a sub-study on gender), modeling and economic evaluation are as follows: 1. Conduct a process evaluation of the OptiMAx intervention to understand how it works, for whom and where; 2. Understand to what extent and how gender-related facilitations and barriers affect the interaction and uptake of intervention, both on the demand side (health-seeking/intervention behaviors) and the supply side (provision of intervention services). 3. Estimate the health impact of the OptiMAx intervention, in terms of nutrition and vaccine-preventable diseases, using mathematical modeling approaches. 4. Quantify the relative costs associated with the OptiMAx intervention compared with the costs associated with existing vaccination activities in Mirriah, Niger, and Ngouri, Chad. 5. Estimate the cost-effectiveness of the OptiMAx intervention in Mirriah, Niger, and Ngouri, Chad.

This is a two-arm, cluster-randomised, phase IV trial conducted in Chad to assess the protective efficacy and impact in real-life conditions of a new strategy for administering the R21/MM malaria vaccine, synchronized within a seasonal malaria chemoprevention (SMC) campaign, among children living in areas of high seasonal malaria transmission. In this study, a cluster is defined as the catchment area of a primary care health centre. In Chad, each catchment area is known as a 'zone of responsibility' (French: Zone de Responsibilité' \[ZR\]). Twenty-six (26) of the total 27 ZRs in the districts of Moïssala and Dembo will be randomized in a 1:1 ratio to receive a 4-dose (3 primary doses + 1 booster) R21/MM schedule either (1) integrated into the routine EPI vaccination program (the "Routine" control arm), or (2) synchronized with an annual seasonal malaria chemoprevention (SMC) campaign (the "Synchronized" intervention arm). Malaria incidence: R21/MM effectiveness will be assessed using the incidence of biologically confirmed clinical malaria (trial primary endpoint). The incidence of clinical malaria will be determined through enhanced surveillance of malaria cases in health centres and hospitals over a 17-month period (August 2025 - December 2026). Coverage surveys: Cross-sectional surveys (cluster sampling) will be carried out to measure R21/MM vaccine coverage, SMC coverage, coverage of other malaria prevention measures, and coverage of other EPI vaccines. Nested case-control study: A sub-sample of children admitted to Moïssala District Hospital with severe clinical malaria will be offered the opportunity to participate in a nested case-control study designed to estimate the individual protective efficacy of R21/MM against severe malaria. Aditionnaly, the INTEGREVAC ancillary study's objective is to evaluate the cost-effectiveness, acceptability and feasibility of the synchronised vaccination strategy in the context of the ongoing COSAV-R21 trial, to inform policy decisions for the effective deployment of malaria vaccines in SMC implementation areas. Methodology and planned work: (i) A qualitative study using in-depth interviews (IDIs) and group discussions with key stakeholders at the national, health facility, and community levels, including caregivers of children eligible for vaccination, in Chad, at several points during the trial. We will explore stakeholders' and beneficiaries' perceptions and experiences of the synchronised SMC vaccination strategy (trial intervention arm) compared to age-based vaccine administration under the routine immunisation programme (trial control arm), as well as considerations for implementing these strategies. Interviews with healthcare providers, including those administering R21 and SMC, and community members will assess the feasibility of implementing the integrated vaccination strategy via SMC. (ii) An economic evaluation including a cost-effectiveness analysis and a nested equity analysis will be conducted. The economic evaluation will include a cost analysis to carefully identify and measure the additional costs associated with adding malaria vaccination to the EPI delivery platform and, separately, to the SMC delivery channel. Analysis of key cost drivers will enable us to identify potential efficiency savings, provide evidence for country funding requests (e.g., to GAVI and the Global Fund) and for the malaria vaccine strategy budgeting/planning process. Cost-effectiveness and equity analyses of each vaccine delivery strategy will provide evidence to help national programmes plan future malaria vaccine delivery and inform global guidance and on methods of delivering these vaccines, while providing valuable evidence on the real-world cost-effectiveness of malaria vaccination. (iii) Impact modelling will estimate the costs, impact, and cost-effectiveness of scaling up the intervention approach to the whole of Chad, under different temporal and spatial scenarios.