Despite available efficacy data on two malaria vaccines designed for broad use, there is little evidence about scalable delivery strategies in areas with seasonal malaria transmission. We propose a multi-site, multi-disciplinary Phase IV cluster-randomized trial in Burkina Faso and Mali to evaluate the effectiveness, real-life impact, acceptability, feasibility and cost-effectiveness of a novel integrated delivery strategy of R21/Matrix-M in areas with highly seasonal malaria transmission.We will compare campaign-style vaccination co-administered during Seasonal Malaria Chemoprevention to vaccination following an age-based strategy in routine Essential Programme on Immunisation activities using a non-inferiority design. We will engage with all stakeholders to co-design the integrated strategy, collect malaria incidence data via surveillance and prevalence via cross-sectional surveys, generate data on coverage, assess feasibility and acceptability among stakeholders and end-users using qualitative longitudinal study methods, and describe the cost-effectiveness of both approaches, with costs and outcomes measured from the societal perspective. We will also use the trial platform to perform post-licensure pharmacovigilance of R21/Matrix-M. The project will ensure translation of results into policy and practice throughout areas of highly seasonal malaria transmission. It responds to SDG3, and is aligned with the Immunization Agenda 2030, particularly by testing a community-based vaccine approach that should reduce the number of “zero-dose” children. By leveraging the SMC platform, we hope to mitigate vaccine hesitancy. Our multi-disciplinary approach aims to generate a comprehensive package of evidence that will allow policymakers to make informed guidelines for malaria vaccine schedules and delivery in the Sahel, at the same time reinforcing health systems and promoting synergies between malaria and vaccination programs in support of the Primary Health Care agenda.

Malaria eradication efforts are severely hampered by the rapid emergence and spread of resistance in mosquitoes due to widespread use of insecticide-based vector-control tools. Recently, we have published a study proposing a novel malaria intervention strategy based on the use of a bacterial strain, Delftia tsuruhatensis TC1 (TC1 for short) and its secreted active component, Harmane (HA). The TC1-intervention interrupts malaria parasite development in mosquitoes without affecting mosquito survival and fitness thereby circumventing selection of resistant mosquitoes. Extensive studies to evaluate efficacy, safety and manufacturability have been successfully completed in both, laboratory and contained semi-field settings and further validate use of the TC1-intervention for malaria control. Although, WHO has established product evaluation pathways and regulatory pipelines for insecticide-based vector control tools these are not suited for TC1 and other ‘TC1-like’ control strategies which do not fall within the ‘main-stream’ conventional category of malaria vector-control tools. To date all vector control tools have been evaluated in cluster randomized control trials (RCTs) to demonstrate epidemiological benefit but RCTs are becoming increasingly difficult and extremely expensive to conduct as standard-of-care increases the heterogeneity between clusters, diminishes the effect size of novel interventions thereby requiring higher numbers of clusters to reliably power studies. An urgent need exists for rigorous and validated entomological metrics which infer epidemiological benefit. This project aims to develop a novel trial for generating the evidence base of the TC1-intervention in open-field settings at the scale of the individual mosquito, to help support the regulatory process and expedite the time between product development and widespread deployment. Additionally, this novel trial could be extrapolated to similar interventions for controlling vector-borne diseases.

Background: Malaria in pregnancy can have devastating consequences, particularly in early pregnancy. Effective treatment in the first trimester can significantly improve maternal and pregnancy outcomes. However, first-trimester pregnancies are generally excluded from clinical trials resulting in new and effective antimalarials being withheld from use in early pregnancy. WHO updated its guidelines in 2022 from quinine to artemether-lumefantrine (AL) as the first-line treatment for uncomplicated malaria in the first trimester. However, there are insufficient data on the benefit-harm of other widely used artemisinin-based combination therapies. Objectives: 1) To generate robust evidence on the safety, tolerability, and efficacy of antimalarials for the treatment of uncomplicated P. falciparum malaria in the first trimester. 2) Translate research findings into treatment guidelines and clinical practice. Study design: a) Phase IIIb, non-inferiority, Bayesian adaptive randomised platform trial comparing pyronaridine-artesunate (PA) and AL in Burkina Faso, Kenya and Mali. Primary outcome: Safety. Secondary outcomes: efficacy and tolerability. b) Formative research to inform innovative trial recruitment and retention strategies, c) Acceptability and feasibility to assess values and preferences of antimalarials during early pregnancy, d) implementation research to explore factors affecting implementation of AL in the first trimester to inform translation strategies, and e) cost-effectiveness of PA vs AL. Impact: The trial will provide critical information on the safety and efficacy of alternatives to AL for treatment in the first trimester, benefiting settings where AL is not used and aligning with WHO's strategy of multiple first-line therapies against antimalarial drug resistance. Results will be translated into policy and guidelines and ultimately ensure that healthcare providers and pregnant women have access to optimal treatment options for malaria in early pregnancy.

The aim of this project is to show how social change dynamics operate from practices that are at the margin of social norms. Margins are understood as practices that deviate from prevailing social prescriptions and statistical trends. These are considered in their ambivalent effect on the dominant norms: on the one hand, they can lead to forms of social exclusion; on the other hand, they confront the prescribed norms and make them evolve. These questions are applied to social situations concerning the family taken in its broad definition. Four thematic lines of research structure this study. The first concerns residential forms and household configurations (female and male alone-parent households, households in which children live without any of their ascendants, and popular rental housing units that include several unrelated households). The second deals with matrimonial status at the margin that is celibacy or free union. The third deals with the specific forms of domestic economy developed within households (circulation of goods and services, economic and domestic arrangements within couples who claim to be equal, care for the elderly and dependents as well as their roles in this domestic economy). The last research line problematizes fertility, infertility and sexuality (forms of marginal sexuality that combine age difference, multi-partnership and material exchanges). This analysis will be done through a cross-fertilization approach between demography and socio-anthropology in three African cities: Ouagadougou (Burkina Faso), Lome (Togo) and Antananarivo (Madagascar). The proposed comparative approach will both highlight data collected during a previous ANR program (FAGEAC) on Ouagadougou and Lome, as well as include the production of novel data on these cities as well as on Antananarivo. Data collection and analysis will be done through a multidisciplinary methodology combining socio-anthropology and demography. Crossing perspectives has a twofold interest: allowing both to reflect on the heuristic issues of each of these disciplines, and to participate in a reflection that discusses the relationship between margins and social norms, social margins and statistics, statistical margins and social norms, statistical norms and social margins. By seeking to highlight innovative social practices and / or invisibilized in research, we investigate the dynamics, the processes of changing standards and the future of norms. Thus, understanding how social innovation proceeds through a joint socio-anthropological and demographic analysis of margins and their impact on norms is the challenge of this research program which will aim to create a constructive bridge between the world of research and transformative actions. Keywords: Family, margins, norms, socio-anthropology, demography, social change, social innovation.