With chest X-ray and molecular tests virtually absent at the primary healthcare care level, where most patients with presumptive TB present in sub-Saharan Africa (SSA), there is a need for accessible, affordable and scalable diagnostic tools for TB triage. CAD LUS4TB represents an interdisciplinary partnership spanning across Western (Francophone) and Southern-African regions with EU countries, aimed at enhancing access to effective TB triage to rule out TB disease among symptomatic adult patients presenting at the primary healthcare level. This initiative focuses on generating population-tailored evidence and advocating for the integration of computer-assisted diagnosis (CAD) using artificial intelligence (AI) to support the implementation of lung ultrasound (LUS) into healthcare policy. Unlike typical vertical triage tests, US has multiple other existing AI-assisted diagnostic tools and can facilitate a multi disease approach after TB exclusion, including for pneumonia and cardiovascular assessment. We propose to externally validate and deploy a novel digital technology adapting image-based analysis tools and software for mobile phone ultrasound applications. AI technology sharing serves as one of its key pillars. The adoption of CAD-LUS requires a comprehensive, interdisciplinary, translational approach to clinical research. Our consortium comprises these key fields, including clinical research, diagnostics, implementation science, social science, health economics and policy translation, as well as data/computer science. It addresses all expected outcomes and contributes to several specific expected impacts of this call. Evidence on the integration of CAD-LUS is expected to accelerate adoption of accessible triage tools for TB in SSA and support achieving target 3.3 of the Sustainable Development Goals. The CAD LUS4TB tool is anticipated to achieve a high diagnostic yield due to its user-friendliness, scalability and possibility to address multiple diseases.

Seasonal malaria chemoprevention (SMC), the administration of sulphadoxine-pyrimethamine and amodiaquine (SP+AQ), during the peak period of malaria risk has proved to be a highly effective malaria control measure in areas where transmission of malaria is highly seasonal; SMC was administered to 45 million children in 2021. Still, malaria remains the main cause of hospital admissions among young children in many parts of the Sahel and sub-Sahel and additional control measures are needed to protect children. The malaria vaccines RTS,S/AS01E, and R21/Matrix, provide a high level of protection during the first few months after a primary series of vaccination, or after a booster dose, but efficacy wanes progressively during the following months and years. Thus, in areas with seasonal malaria transmission, one potential use for these vaccines, which provide a high but relatively short period of protection, is administration of an annual booster dose given prior to the malaria transmission season in children who have received three priming doses of the vaccine in the first year of life. However, there is a debate about the best approach to delivery of the booster doses and the main objectives of this study are to determine whether annual booster doses of RTSS,AS01E vaccine administered pre-transmission season through a mass campaign will achieve better coverage and higher impact on the incidence of malaria than pre-transmission booster doses delivered by an EPI programme at vaccination centres. This will be a pragmatic implementation study involving two cohorts of children. Two districts that have comparable malaria epidemiology, social structure, coverage of EPI vaccines, and access to treatment will be identified in both Mali and in Guinea from the list of districts that are selected for roll out of RTS,S/ASO1E vaccine by the Ministry of Health. This project will provide important information on the optimum delivery which could save many lives.

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.

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.