The main concern of clinicians when addressing sick patients is to promptly identify -i.e., “not miss”- those at higher risk of severe disease, so as to prioritize their care and better target therapeutic interventions. Unfortunately, risk-stratification practices for infections remain suboptimal and prone to misclassification, leading to adverse outcomes and misallocation of resources, particularly in children (and even more so among newborns) from Sub-Saharan Africa (SSA). We recently developed “B-Triage”, a point-of-care rapid triaging test, designed for the quantitative assessment of sTREM-1, a biomarker of sepsis, and a highly performing prognostic marker, irrespective of underlying disease. Levels of sTREM-1 stand out as a quantitative and independent predictor of severity and death in all-cause infections, being superior to other markers and clinical scores, showing promise also for risk-stratification of non-communicable diseases. We propose to specifically validate B-Triage for risk-stratification of all cause sickness in the newborn, the age group concentrating ~50% of all child mortality. ACROBAT-newborns aims to continue and accelerate the valorisation of our device, with clinical studies in Mozambique, Ethiopia, Uganda and Gabon; the industrialization of its prototype; and a go-to market strategy for SSA. The project includes strong components of health economics and impact assessment, as well as socio-behavioural sciences (usability, acceptability, and feasibility studies), with the overarching aim of generating the necessary evidence to support B-Triage’s introduction to the African market. The proactive use of our device for risk-stratification of the sick newborn at first clinical presentation, will determine, objectively and with high precision, those at risk of severe outcome and death, resulting in improved outcomes and survival, and an optimized use of healthcare resources, including antibiotics and high value therapeutics.

We will establish for the first time in NTDs an adaptive clinical trial platform and improve clinical research infrastructure in four SSA countries. A drug acting safely on multiple helminths species would be a major leap to tackle NTDs and enable the WHO RoadMap (eWHORM). The cheap and freely-accessible pan-nematode drug oxfendazole (OXF) has such potential. Given the limited portfolio of anthelmintic drug candidates, eWHORM will assess its efficacy in an adaptive clinical trial for simultaneous evaluation against onchocerciasis, loiasis, mansonellosis and trichuriasis. Thus not only the largest group of NTDs, but also diseases that are not (yet) listed will be adressed. This design significantly reduces patient numbers, development time-frames and enables treatment of co-infections. Combined with our highly sensitive molecular tests, we provide a patient-centric approach providing tools for targeted treatment (test and treat) and precision mapping for elimination programs. Strengthening of early career scientists in SSA in all aspects of clinical trial conduct and research including data management, simulation and statistical analysis, will be fostered by introducing a master and PhD program, a mentorship program as well as several webinars. An open-source virtual training and assessment tool for diagnosis of NTDs will complement the knowledge transfer to remote areas in SSA. The consortium encompasses an interdisciplinary partnership from eight different countries (Germany, the Netherlands, Austria, Switzerland, Cameroon, Gabon, Tanzania, and DRC). Each group brings unique knowhow and recognized complementary experience to the project to ensure sustainable capacity building within SSA countries. Through joint development of – and training in – modern, regulatory clinical trial conduct, adaptive clinical trial design and state-of-the-art diagnostics, we will strengthen SSA researchers and clinicians to respond to persisting and future health challenges.

The world is facing the silent “pandemic” of antimicrobial resistance (AMR). Central Africa has the highest mortality rate (23.5 deaths/ 100,000) attributable to AMR in the world. Research is desperately needed to better understand the burden of AMR in this region, and it is vital that this work is done by local researchers who will be the future leaders of scientific and clinical research in central Africa. The overall aim of the Central Africa Training Platform for Clinical Research on infectious diseases (CATCR) project is to produce essential, world-class research in central Africa, for central Africa, by central African people. To achieve this, it is crucial that the critical mass of PhD and PostDocs in central Africa is increased. Therefore, the consortium will (1) develop a multifaceted training programme on infectious diseases focusing on AMR for MSc, PhD and healthcare professionals; (2) develop a clinical fellowship programme of recruitment, training, evaluation and retention; (3) research the lack of knowledge on antimicrobial usage trends in patients with parasitic infections; (4) research the causal link between prevalence rates and influencing factors of carbapenemase-producing Enterobacterales (CPE) and occurrence of AMR in humans and livestock; and (5) research to understand the prevalence of tuberculosis (TB) and drug-resistant TB characteristics in Central Africa. Finally, (6) the project will focus on communicating, and disseminating research results. Through CATCR, talented researchers, clinicians and health care professionals working on AMR in central Africa will benefit from access to fully-funded fellowships to complete ground-breaking research. Public and regulatory authorities in Africa will use the research and newly established fellowships to develop vital AMR action plans and to increase the critical mass of researchers in the region will ultimately lead to benefits for patients and citizens of central Africa.

Lassa fever (LF) is an acute febrile illness associated with bleeding, organ failure, and shock caused by Lassa virus. LF causes outbreaks in West African with in-hospital mortality up to 12%. Challenges in the clinical care of patients are multiple due to the limited availability of LF molecular diagnostics, the risk for nosocomial transmission, and the limited treatment options.There are currently no safe and effective treatment options available for LF, except ribavirin, the efficacy of which is debated. The clinical development and accessibility of effective treatment options would be a game-changer towards reducing mortality associated with this disease and limiting its socio-economic impact. Nigeria is the country by far most affected by LF in the world with about 80% of global cases. The INTEGRATE consortium builds on a more than 15 years lasting highly successful collaboration between leading European and West African institutions focusing on the joint priority to better understand, manage, and combat LF in West Africa. The overall objective of the INTEGRATE project is to establish a GCP-compliant adaptive clinical platform trial in West Africa (Nigeria and other countries) to test the efficacy, tolerability and safety of repurposed and novel drug candidates for the treatment of LF. To address this objective, we focus our activities on 3 specific objectives: - to develop and implement an adaptive randomised controlled phase II-III clinical platform trial evaluating drugs with proven preclinical activity against LF. - to build capacity for sustainable and independently conducted clinical research in West Africa by developing site, laboratory and medical care capacity through North-South and South-South technology transfer and training. This activity encompasses capacity building of the lead Nigerian institution in GCP compliant clinical trial sponsorship. - to engage communities with the proposed work plan and to assess acceptability of the trial.

The proposal, VSV-EBOVAC, directly addresses the topic 1 of the IMI2 call on Ebola by supporting the clinical development of a highly promising new Ebola vaccine candidate, the vesicular stomatitis virus (VSV)‐ vectored Zaire Ebola vaccine (VSV-ZEBOV). In non-human primates, a single dose of VSV-ZEBOV elicited a strong (100%) and long-lasting protective efficacy against Ebola Zaire infections. Developed by Public Health Canada and manufactured by NewLink Genetics, VSV-ZEBOV was thus selected by the World Health Organization (WHO) as one of the 2 most promising vaccine candidates. To accelerate its clinical development, the WHO has organized a consortium and supported the organization of parallel first-in-man Phase I/II clinical trials, both in Europe and Africa. The primary objectives of these trials, initiated mid-November 2014, are to study the safety and antibody-inducing capacity of various doses of VSV-ZEBOV in European and African populations. We propose to build upon this asset to acquire new and critical knowledge of the innate and adaptive immune responses elicited in humans by VSV-ZEBOV vaccination, with specific emphasis on trancriptomics and metabolomics signatures. To this aim, we have constructed a consortium including representatives from the vaccine manufacturer, scientists of the 3 main clinical sites (Switzerland, Gabon, Kenya) and world-leaders in immunology and partners of ADITEC, a large FP7- supported collaborative research programme aiming to accelerate the development of novel, powerful immunisation technologies for next-generation vaccines. We propose an ambitious program using cutting-edge technologies to perform an in depth characterization of the clinical samples harvested before/after VSV-ZEBOV immunization of 200 volunteers in Switzerland, Gabon and Kenya, and to extend the recently initiated clinical studies up to 12 months to identify the signatures and determinants of persistent immune responses.