Gene therapy advancements have shown promise in treating chronic conditions like HIV and Sickle cell Anaemia and have the potential to greatly reduce the burden of disease in Sub-Saharan Africa which is plagued with a double burden of communicable and non-communicable diseases. These treatments have the potential to reduce the burden of disease for the populations for which they are targeted and the cost of treatments for governments. In Sub-Saharan Africa, there are largely no or unclear regulatory frameworks for clinical trials using Gene Therapy products. As pioneers setting up frameworks for regulatory oversight of clinical trials using Gene and cell-based therapy products, Uganda and Tanzania will be able to share this knowledge through regional platforms to support other countries in the region to put in place similar regulatory frameworks. Additionally researcher workshops and course developed on Gene Therapy Products will build capacity among researcher, regulators and the public. Pharmacovigilance in clinical trials for safety of trial participants and to accurately characterize the safety profile of the drug for the targeted patient population. Safety monitoring in clinical trials in the region, currently faces challenges associated with health system challenges, investigator awareness, poverty and limited access to diagnostic tools. Additionally, there is limited investigator awareness of of their responsibility to the patients with regard to monitoring and treating and accurate reporting of serious adverse events during clinical trials. The results of this project will also provide a basis to sensitize investigators/sponsors and engage policymakers on the requisite health systems reforms to create a safe environment for the conduct of clinical trials with the ultimate goal of accelerating research, registration and access to these new medicine technologies.

IMCI-PLUS is an inter-disciplinary, Pan-African-EU research partnership, with emphasis on capacity strengthening and mutual learning, to improve management of pediatric lower respiratory tract infections (LRTI)–the leading cause of child morbidity and mortality in Sub-Saharan Africa (SSA)–by working towards the adoption of point of care lung ultrasound (PLUS) into healthcare policy and routine clinical practice. Current Integrated Management of Childhood Illnesses (IMCI) guidelines fail to differentiate between uncommon severe bacterial infections and more ubiquitous self-limited viral illnesses; inappropriate antibiotic use is thus widespread and a key driver of antimicrobial resistance. Equally, tuberculosis cases are missed. The World Health Organization has identified the rigorous evaluation of PLUS to treat children with LRTI as a research priority, especially its health/economic impacts and operational barriers. Including diverse settings within 3 SSA countries (Senegal, South Africa, Tanzania), IMCI-PLUS determines real-life health (antibiotic prescription and clinical outcomes) and economic (cost and cost-effectiveness) impact of integrating PLUS into LRTI management through a prospective randomised controlled trial, combined with evidence from implementation research among 8500 children. Stakeholder engagement to assess acceptability and feasibility informs a co-designed implementation package with key uptake barriers explored and addressed. A main barrier—healthcare provider skills gaps—is innovated through AI-enabled automated PLUS interpretation. IMCI-PLUS generates tailored clinical decision tools integrating PLUS to manage LRTI syndromes across a range of epidemiological and healthcare settings. A comprehensive, integrated translational research framework, focusing on mutual learning by involving stakeholders and patients meaningfully during all evidence generation and translation stages, enables adoption of research findings into policy and practice.

Insufficient reductions in maternal and neonatal deaths and stillbirths in the past decade are a threat to achieving the Sustainable Development Goal 3. Overcoming the knowledge-do gap to ensure implementation of known evidence-based intervention during the intrapartum period – the period from onset of labour to immediately after childbirth – has the potential to avert at least 2.5 million deaths in mothers and their offspring annually. Our ALERT approach targets this period and will develop and evaluate a multifaceted health system intervention to strengthen the implementation of evidence-based interventions and responsive care in Sub-Saharan African hospitals, where 40-50% of all births in the region take place. The ALERT intervention will include four main components: i) end-user participation through narratives of women, families and midwifery providers to ensure co-design of the intervention; ii) competency-based training; iii) quality improvement, supported by data from a clinical perinatal e-registry; iv) empowerment and leadership mentoring of maternity unit leaders complemented by district based bi-annual coordination and accountability meetings. We will apply a gender lens to explore constraints in intrapartum care in the context of the multidisciplinary teams providing maternity care. Repositioning midwifery with its preventive, promotive and curative aspects is a cross-cutting theme. We will evaluate the intervention through a stepped-wedge design, the primary outcome being in-facility perinatal (stillbirths and early neonatal) mortality. Our nested realist process evaluation will help to understand what works, for whom and under which condition. An economic evaluation will report on scalability and costs. Our research aims to inform programming for the Sustainable Development Goals and Every Women Every Child Agendas of the United Nations to support Universal Health Coverage and patient-centred care which will be relevant beyond the project focus