Annually, almost 500,000 children under 5 years die from malaria in Africa. Timely access to effective antimalarial therapies is life saving as treatment with pre-referral rectal artesunate (RAS), followed by injectable artesunate and 3 days treatment with ACTs leads to an observed 96% reduction in mortality. Though recommended by the WHO for years, RAS deployment is very limited. The full treatment paradigm is not always feasible when access to primary healthcare facilities is limited due to lack of transport, non-availability of services, and cost. Rollout has recently been paused as outcomes data is incomplete in these contexts making the development of best practice recommendations challenging. Hence the relevance of the proposed study. The proposed project is an observational, non-inferiority study in Zambia and DRC. Community Health Care Workers will identify/diagnose, treat and follow up patients with (severe) malaria as part of integrated community case management. We will compare the efficacy of a treatment regimen consisting of pre-referral RAS, then post-referral injectable artesunate, followed by three days of ACT versus a regimen consisting of RAS alone followed by three days of ACT in remote areas. We will compare recurrence rate between the two regimens at Day 28, the number of lives saved, the risk of generating drug resistance. We will assess and mitigate operational and institutional facilitators and barriers in all stakeholders (patients, caregivers, health care providers, regulators, malaria experts) and recommend sustainable policies for this remote context. This generated evidence will support policy development and implementation. The proposed consortium brings together vital experience in the rollout and deployment of rectal artesunate, study design and execution, social science, data collection and management, stakeholder engagement and translation of research results into clinical practice.

An effective and strong regulatory system for health technologies is critical, especially during epidemics and pandemic situations. The demand for rapid approval and application of a variety of health technologies including diagnostics and medicines during COVID-19 has reawakened the world to the urgent need to have resilient regulatory capacities that can respond in a timely manner with corresponding efficiency. National Medicines Regulatory Authorities and Research Ethics Committees are duty bound to prepare and be ready to respond in any health emergency. Through EDCTP-2-funded projects namely SMERT, PROFORMA, PAVIA and ASCEND, substantial progress has been made on strengthening some procedures for clinical trial control and pharmacovigilance. These projects have enabled Tanzania to attain WHO Maturity level 3, making it a role model in East Africa. Despite of this, health technologies regulation in Tanzania has struggled to cope with emergencies as witnessed in the COVID-19 pandemics due to limited capacity in the area of Research Ethics, therapeutics, vaccines, medical devices and other health technologies. We now propose BREEDIME to further build our capacity in the context of epidemic and pandemic preparedness. BREEDIME will enable Tanzania to achieve rapid response clinical trial regulatory capacity for therapeutics, vaccines, and diagnostics; capacity for post-market evaluation and appraisal of health technologies; establish research ethics framework for electronic health data and materials storage, access and sharing within and outside the country; and establish a south-south learning centre in clinical trials regulatory and ethical review capacities. These objectives will be achieved through engagement of stakeholders in academia, civil society, public and government to generate evidence to inform new regulatory guidelines. This will strengthen health technologies regulation and will enable rapid access to health care and technology during emergency. Rwanda, which recently established her Food and Drugs Agency will become the first mentee under the BREEDIME south-south networking in ethics and medicines regulatory capacity building. The impact of the outputs of this study will be ensuring safety of pre- and post- registration health technologies in Tanzania and East Africa at large.

The African Great Lakes region is one of the most densely populated areas in Africa and also one of the areas globally with the highest biodiversity, and forced or voluntary migrations. Very limited information is available on the prevalence and epidemiology of infectious diseases, especially gastrointestinal diseases and antimicrobial resistance that has been very understudied. Logistically it is difficult to sample and conventionally study infectious diseases in the area and such studies have limited real-time value locally. In this study we will take full advantage of the potential offered by combining field-deployable nanopore sequencing combined with metagenomics and lap-top bioinformatics, to establish frontline sequencing at remote sites and linking this with central sharing of analytic output. Newly developed bioinformatics solutions by us have made it possible to perform simple bioinformatics analyses in real-time using lap-tops and subsequently share the analytic output simply using the mobile net, avoiding the need of transferring large amounts of data and access to high-performance computing. In GREAT-LIFE we will establish sequencing across six countries in the region and use this to study the abundances of AMR in villages and refugee camps. Linking this with spatial and temporal epidemiological data will enable us to identify locally relevant drivers for AMR and provide data for changing empiric treatment and policies. In addition, we will utilize sequencing directly on GI samples to identify the causative agents (and their AMR) both to provide data for policies, but also to provide immediate results for direct patient care in the frontline. We will educate a number of people in the very frontline to utilize field-sequencing and bioinformatics, as well as more advanced bioinformaticians and epidemiologist centrally. The data generated will be linked in real-time through a central hub in Tanzania to public health authorities for actions.

Many HIV vaccine concepts and several efficacy trials have been conducted in the prophylactic and therapeutic fields with limited success. There is an urgent need to develop better vaccines and tools predictive of immunogenicity and of correlates of protection at early stage of vaccine development to mitigate the risks of failure. To address these complex and challenging scientific issues, the European HIV Vaccine Alliance (EHVA) program will develop a Multidisciplinary Vaccine Platform (MVP) in the fields of prophylactic and therapeutic HIV vaccines. The Specific Objectives of the MVP are to build up: 1.Discovery Platform with the goal of generating novel vaccine candidates inducing potent neutralizing and non-neutralizing antibody responses and T-cell responses, 2. Immune Profiling Platform with the goal of ranking novel and existing (benchmark) vaccine candidates on the basis of the immune profile, 3. Data Management/Integration/Down-Selection Platform, with the goal of providing statistical tools for the analysis and interpretation of complex data and algorithms for the efficient selection of vaccines, and 4. Clinical Trials Platform with the goal of accelerating the clinical development of novel vaccines and the early prediction of vaccine failure. EHVA project has developed a global and innovative strategy which includes: a) the multidisciplinary expertise involving immunologists, virologists, structural biology experts, statisticians and computational scientists and clinicians; b) the most innovative technologies to profile immune response and virus reservoir; c) the access to large cohort studies bringing together top European clinical scientists/centres in the fields of prophylactic and therapeutic vaccines, d) the access to a panel of experimental HIV vaccines under clinical development that will be used as benchmark, and e) the liaison to a number of African leading scientists/programs which will foster the testing of future EHVA vaccines through EDCTP