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.

Despite of the successful advances achieved to date in the fight against the COVID-19 pandemic with the development of vaccines and therapy, the worldwide propagation of SARS-CoV-2 has resulted in the rapid evolution of this virus and in the emergence of variants of concern (VOC) that may dampen the efficacy of the first generation vaccines. To tackle the challenges associated with the VOC, the CoVICIS program is proposing a global approach with a powerful state-of-the-art virologic and immunologic platforms coupled with large genomic surveillance studies and diverse cohorts in EU and SSA. This allows CoVICIS to contribute to the early identification of emerging VOC and address key unanswered questions regarding i) the susceptibility to infection with VOC after a prior infection in the setting of a long-COVID or after vaccination with different vaccines, ii) the risk posed by VOC in immunocompromised patients, and iii) the modalities of infection and immune responses in children. The diversity of the cohorts provides a unique opportunity to study virus evolution in different settings, where SARS-CoV-2-specific humoral and cellular immune responses are predicted to vary very significantly. Beyond the genomic surveillance, the ground-breaking research and innovation of the program is the characterization of virologic and immunologic properties of VOC and the identification of immune correlates of protection after disease or vaccination. CoVICIS’ ambitious goals are only achievable thanks to the existing population studies and cohorts funded by national and international public agencies and public-private partnerships, and the combined collective expertise of CoVICIS partners in the fields of epidemiology, genomics, virology, immunology, data science and public health.

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.

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.

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.