Mpox can cause severe complications in vulnerable groups such as pregnant women and children, necessitating targeted public health interventions and vaccine trials in these populations. Limited data suggest the MVA-BN vaccine is safe for pregnant women and likely poses no risk to breastfed infants, but comprehensive human data are lacking. Trials in endemic areas are crucial for evaluating the vaccine's safety and efficacy in real-world settings. Vaccine hesitancy, exacerbated by misinformation and distrust in healthcare systems, poses a significant challenge, especially in the Democratic Republic of the Congo. Pregnant women are particularly affected by concerns about vaccine safety, which influences their willingness to vaccinate. Addressing these concerns through targeted communication and community engagement is vital. A proposed phase 3, randomized trial will assess the safety and immunogenicity of the MVA-BN vaccine in healthy pregnant and postpartum women and in infants/children (6-24 months old). Additionally, a qualitative study on vaccine hesitancy will inform the trial design and implementation, aiming to enhance vaccination uptake in these high-risk groups.

In suv-Saharan Africa (sSA), most government-run hospitals aim to follow WHO or national syndrome-based guidelines. Clinical syndromes, such as ‘severe pneumonia’ are designed to be sensitive for pathologies like invasive bacterial disease that require specific treatments to prevent death. However, low specificity means that a far wider group of children is captured by a syndrome definition including many with a self-limiting infection and very low risk of death. Currently, decisions regarding admission, discharge, and escalating or de-escalating antimicrobials are typically made by staff with limited paediatric training, very often interns, and current guidelines have very limited or no advice on de-escalation and discharge. These factors contribute to antimicrobial over-use, overly broad-spectrum prescribing, and unnecessarily prolonged treatment ‘to be on the safe side’. Excessive duration of antibiotic treatment means a greater risk of acquiring AMR from the hospital environment, significant costs to health providers and families, overcrowding, a low nurse:patient ratio, and reduced care for higher risk children. We propose that major reductions in antibiotic use, exposure to the hospital environment and transmission of AMR can be achieved by risk stratified care enabling very low-risk children admitted to hospital to be cohorted away from longer-stay patients, stop antibiotics and go home earlier with inexpensive phone follow up. We will engage policymakers, undertake mathematical modelling of antimicrobial usage, AMR transmission and costs across sSA within risk strataand conduct a trial of risk stratified care, and develop a tool 'PPS-plus' for monitoring of AMR transmission through simple cross sectional surveys. Relevance to the work programme includes combatting the major global threat from AMR through identification of personalised treatment options, a better evidence-base for policymaking, and digital tools to optimise clinical workflows.

The overall goal of COMECT is to coordinate activities across Europe’s strategic adaptive platform trials (APTs) and cohort studies (CS) on infectious diseases (IDs) with epidemic or pandemic potential, by overseeing and facilitating dialogue, sharing of good practices, promoting collaboration and coordination across studies and providing updated information on initiatives and innovation in ID clinical research. COMECT will build on and strengthen existing networks and infrastructure. These include EU-funded coordination mechanisms and networks, namely the Trial Coordination Board (TCB), Joint Access Advisory Mechanism (JAAM), the Cohort Coordination Board (CCB), and the ECRAID Coordinating Comittee. COMECT will develop a visible, well-defined coordination mechanism to highlight Europe's capacity and competence as an attractive base for clinical research. COMECT will deliver: 1) an expanded, combined European coordination mechanism that will work on harmonizing research initiatives, exchange of good practices, and stakeholder engagement across ID clinical studies in outbreaks and during inter-epidemic phases; 2) a strengthened JAAM to support coordination through independent scientific assessment of compounds/vaccines and recommendations for APTs to evaluate the new compound in new or adapted platform trials; 3) the mapping of stakeholders and their respective activities relevant to APTs and CS; 4) a harmonised approach cross-study identification, assessment, and reuse of participant-level data from European APTs and CS; 5) coherent communications and stakeholder engagement across all activities; 6) a sustainability plan for the continuation of activities beyond the funding period. COMECT will quickly adapt coordination efforts to a changing research landscape and to new ID threats. COMECT will operate in close collaboration with other emergency preparedness mechanisms, such as HERA, EMA, GLOPiD-R and the European Pandemic Preparedness Partnership.

Pregnant women, children and adolescents are priority populations in the global public health response to the epidemics of HIV, TB and HCV.The high burden of intersecting epidemics of these 3 infections pose a major public health challenge to Russia and the broader European region. The global health goals of ending AIDS, reducing TB deaths and new HCV cases by 90% by 2030 can only be realized if the unique health needs are considered and targeted research to these priority populations is undertaken to optimise the impact of innovations in diagnostics and treatment. REACH builds on long-standing, successful collaboration between European clinical research networks with track records of delivering innovative research across the three infections with leading collaborators from 7 centres of excellence in Siberian, Northwestern and Central districts of the Russian Federation. The goals of REACH are: 1)To conduct joint research to better understand the epidemiology, disease progression, treatment and outcomes of HIV, TB and HCV mono and co-infections among pregnant women, children and adolescents in the RF: 2)To exchange knowledge, build capacity and prepare for future collaborative research on HIV, HCV and TB in children, adolescents and pregnant women in the RF, including women and young people. REACH will fill the knowledge and data gaps on HIV epidemic affecting children, adolescents and pregnant women across Russia and provide new data on long-term ART toxicity, HIV resistance, HCV and TB coinfections and comorbidities in this setting. It will develop future studies of new diagnostics and preventive TB treatment and the use of novel therapies for HCV in children in real-world settings. REACH will promote geographic expansion of the collaborative research in maternal and child health in Europe with a broad and long-lasting impact. It will also build capacity for improved coordination and integration between European and Russian research centres beyond 2020

The 2.5 million children and adolescents living with HIV (CALHIV), most residing in sub-Saharan Africa, have unacceptably high rates of late diagnosis, treatment failure and death, compared to their adult counterparts. CALHIV are a vulnerable group who have been left behind adults in testing new treatment options, different modes of ART delivery, novel diagnostics and adherence strategies. The CHAPAS-5 trial is a sustainable multi-country adaptive platform trial in Mozambique, Uganda and Zimbabwe, to assess novel treatment regimens in ART-naïve and treatment-experienced viraemic children aged 4 weeks to <20 years of age. CHAPAS-5 employs an innovative Personalised Randomised Controlled Trial (PRACTical) design, randomising participants between appropriate ART regimens based on their clinical status, ART history, genotypic resistance and drug availability by weight band. The trial's primary outcome is: alive with viral load <400 c/mL at 48 weeks. CHAPAS-5 will evaluate novel oral and first generation long-acting injectable (LAI) treatment regimens and, subsequently, through its adaptive design, second-generation promising long-acting therapeutics. Nested pharmacokinetics will evaluate dosing for children, as needed. Social science, health economics and capacity strengthening are fully integrated through the project. Workpackages will explore options for community-delivery of LAIs, and employment of diagnostics, including POC CD4, near-POC viral load and resistance tests. Community groups and young people will be involved in our dissemination and communication activities. We will exploit project outputs and facilitate technology transfer for treatments and diagnostics from innovators to African manufacturers. CHAPAS-5 aims to improve health and well-being of CALHIV, to inform clinical guidelines, and to strengthen health systems through capacity development. Our trial platform will provide a long-term resource for studies seeking to improve outcomes in CALHIV.