In 2022, the World Health Organization (WHO) recommended bedaquiline (BDQ)-based, all-oral regimens including pretomanid (Pa), linezolid (L), and moxifloxacin (M) (BPaLM), lasting 6-9 months However, BDQ-resistance is rising dramatically and threatening these advancements. Mozambique has reported BDQ resistance in 28% of MDR-TB isolates in 2024, up from 3% in 2016 and at 10% in South Africa (Ndjeka N, personal communication). Spread of BDQ-R TB must be slowed by antibiotic stewardship through more rapid, accurate, and near-patient diagnostics, and optimized management; until new treatment options with drugs that have no pre-existing resistance or are able to overcome small shifts in MIC will be available. The proposed EX-DR TB project includes diagnostic capacity strengthening, adapting treatment recommendations, and a trial of two new regimens composed of new drugs. The EDCTP EX-DR TB project will: 1. Develop treatment recommendations by a Delphi process with stakeholders - to make use of targeted next generation sequencing (tNGS) that is being rolled out by most national TB programmes - this will yield short-term benefit for patients and NTPs; and will slow the spread of BDQ-resistant bacteria; 2. Rigorously evaluate two treatment regimens composed of new drugs, in a phase 3 clinical trial conducted to the highest regulatory standard – this will be the main focus of EX-DR TB. The trial objective will be to move a regimen towards regulatory approval by FDA and/or EMA, and WHO if supported by results. Thus, EX-DR will create the tools for containing the nascent epidemic of BDQ-R TB and make them available to healthcare providers and TB Programmes. EX-DR TB will be embedded in a larger coalition of funders and partners focused on implementing and evaluating diagnostics and performing the trial beyond of the EDCTP funded area.

Violence Violence is an important societal challenge and associated with poor health outcomes across the life-course. Studies find consistent associations between childhood violence exposure and risk for victimisation and perpetration in adulthood, particularly across generations. Thus far, we lack an evidence-base to understand the underlying mechanisms of intergenerational violence transmission as well as potential for prevention in regions with high rates of interpersonal violence such as sub-Saharan Africa. This marks a major evidence gap and a compelling need. This study will use a mixed methods approach to develop the first-known empirically-generated theoretical framework on intergenerational violence transmission. It will do so using three approaches never utilised in the region: 1) using data from a 1-year longitudinal study of 1800 adolescents in South Africa (interviewed in 2010/11 and 2011/2012) it will re-trace original participants, re-interview them as young adults aged 20-27, recruit their children (n~211) and previous primary caregivers (n~540) and conduct in-depth qualitative work on a sub-sample of families to identify mechanisms of violence transmission across generations and genders, 2) it will investigate the effect of the prevalent structural risk factors poverty, poor service access and delivery and the HIV epidemic on violence transmission, and 3) it will examine the effect of protective interventions and policies using quasi-experimental methods. This study will transform our understanding of the causes, effects and potential prevention mechanisms of intergenerational violence transmission through cutting-edge social science research. This is an ambitious research agenda of a complex behaviour and is characterised by methodological and theoretical innovation never used in the region before. The methodology presents high risks balanced by the potential for ground-breaking scientific and social impact for violence research and prevention.

Reducing HIV is key 2030 SDG target. In Africa, HIV prevention research has focused on young women yet heterosexual men, vulnerable due to their mobility, remain WHO priority. Long-acting injectable cabotegravir (CAB-LA) and on-demand, oral pre-exposure prophylaxis (PrEP) have not been evaluated in such men who are not in-line to receive either. Building on our EU studies men want on-demand PrEP and CAB-LA (referred to as new PrEP options). This project using RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance), uses rapid assessment followed by implementation trial. Objectives 1: Catalysts/barriers across local and regional contexts that could influence uptake of new PrEP options by mobile men a. Qualitative assessment mobility patterns of men, knowledge/ perceptions of PrEP effectiveness b. Policy analysis at local and national level 2: Assess implementation effectiveness of new PrEP options by comparison of retention in care, effective use and expressed choice Open-label study of 400 men from mobile groups in South Africa and Uganda randomised to oral TDF-FTC or CAB-LA over 9 months, then access to both to 18months 3: Preferences of mobile men amongst new PrEP options a. Adoption of new PrEP options b. Barriers in non PrEP acceptors c. Patterns of PrEP use d. Participant/ staff / community reflections 4: Reach and implementation of PrEP for mobile men amongst service providers to inform scale-up a. Reach of PrEP b. Feasibility of delivering PrEP in different settings c. Fidelity of PrEP delivery in practice d. Service-level needs and adaptations to implement PrEP Objectives 3 and 4 use mixed methods in users and service providers. Objective 5: Affordability, cost and cost effectiveness of new PrEP options using HIV synthesis model This first multi-country study of on-demand PrEP and CAB-LA in men in Africa provides evidence for guidelines change, inform scalability, and provide operational tools for PrEP implementation.

ENBEL will support EU policy making by bringing together leaders in climate change and health research. We do so by coordinating a network of major international health and climate research projects under the Belmont Forum’s Collaborative Research Action (CRA), Societal Challenge 1 and 5 of EU’s Horizon 2020, and other national and international funding schemes. The network will develop evidence syntheses and co-produce with stakeholders a series of tailor-made knowledge products. The project will engage with EU policy advisors to translate science into policies that help shape low-carbon economies and build climate resilience in member countries while supporting EU diplomacy and development strategies. The overall concept of ENBEL is a bottom-up approach to networking and cooperation across the often separate worlds of climate and health research communities. This can have major impacts on knowledge production and policies. ENBEL brings together a consortium whose work generates actionable knowledge on how climate change-health risks will develop under global warming, what are the social costs and effective, cost-efficient and equitable mitigation and adaptation strategies. ENBEL focuses on three major climate change related health hazards: environmental and occupational heat, air pollution (particularly from wildfires) and climate-sensitive infectious diseases, with specific attention given to high risk groups and populations within Europe, and in Africa/Asia-Pacific region. ENBEL will support a knowledge management platform of EU funded research on climate change and health is two ways: A) build and manage a web-based knowledge platform of health impact of climate change by using innovative tools such as video, photos, maps and infographics; B) connect to existing and recognised knowledge platforms.Through our partners in low-and middle-income countries (LMIC), ENBEL will support, strengthen and establish channels for collaboration and capacity-building in LMIC.

Lower respiratory tract infections resulting from seasonal epidemics and pandemics are among the leading causes of death globally. There is a paucity of treatment options for viral respiratory pathogens and patient care remains largely supportive. This underscores a desperate need for identifying novel targets for prophylactic/treatment interventions and early prediction models of disease outcome to personalise treatment. The REACT consortium ? uniting high-level experts in virology, immunology, clinical medicine, epidemiology, and bioinformatics ? will assess genotypic, high-dimensional immunophenotypic, demographic and clinical data in the context of disease course to define host-pathogen interactions of viral respiratory tract infections, focusing on the predominating viruses i.e. influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In characterised, ethnically diverse clinical cohorts comprising patients with varying disease severities, we will genotype both virus and host, map deep immunological phenotypes spanning cellular, humoral and innate immunity, and characterise host responses in human nasal epithelial organoid models following viral infection. Novel bioinformatics approaches that include knowledge discovery and machine learning will be used to integrate and analyse multidisciplinary datasets to assess the individual and combined impact of factors on disease phenotype. Information on the deep characterisation of the dynamics of the immune responses to the chosen viruses and identified factors critical for viral control and immune protection will be made available on a dedicated project website to clinicians, researchers, health authorities, and public. This will provide direct and immediate access to our findings for further development of personalised treatment, therapeutic targets and vaccines in future trials and clinical practice to improve the wellbeing of the EU population and beyond.