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.

Pregnant women in Africa are exposed to considerable health risks, with parasitic infections being a major threat. Schistosomes, soil-transmitted helminths, and malaria parasites are highly prevalent and polyparasite infections are common. In pregnancy, besides iron deficiency parasites are a key factor causing anaemia associated with an increased risk of maternal and infant morbidity and mortality. More than 50% of the pregnant women are affected by anaemia and an estimated 0.8 million pregnant women globally have severe anaemia. Antenatal care is a health program to regularly deliver health services including preventive measures with the aim of improving maternal and newborn health. In terms of fighting parasitic diseases, WHO recommends to preventively treat soil-transmitted helminths, schistosomes and malaria parasites. In many endemic sub-Saharan African countries, however, these recommendations are often only partially implemented and not consistently applied in daily antenatal care. Reasons are multifactorial but hesitation in administering multiple drugs this vulnerable population and the complexity of integrating the use of multiple drugs into the antenatal care schedule. On the other hand, data is accumulating that outweighs the potential risk of antiparasitic drug intake versus health benefits. The project aims to increase the uptake and integration of presumptive antiparasitic treatment during pregnancy to combat anaemia and improve health outcomes for pregnant women and their babies in sub-Saharan Africa. To this end, a multi-country trial will assess the safety, tolerability and efficacy of co-administered antiparasitic drugs. Pharmacokinetic data, cost-effectiveness analysis and public health stakeholder’s involvement will further strengthen the case for future implementation of co-administered antiparasitic drugs in antenatal care schedules. Training in African scientific leadership will contribute to a critical mass of highly trained professionals.

Infections with parasitic worms (helminths) continue to cause a massive global health burden. Yet, effective vaccines to enable control and elimination of helminth infections do not exist. Primary reasons for this are that target discovery approaches are not well-developed, protective immune mechanisms are only partially clarified at best, production platforms tailored to specific helminth vaccine requirements are not available, and a pipeline for selecting and rapidly progressing pre-clinical and clinical vaccine candidates is generally lacking. Moreover, controlled human infection models are only now being developed and optimized for some of the most important human helminths. These models have not yet been widely implemented in vaccine development programs to date. The objective of WORMVACS2.0 is to establish an effective pipeline to support helminth vaccine development focusing on schistosomes and hookworms, and ultimately the control and elimination of some of the world’s most devastating and persistent Neglected Tropical Diseases (NTDs). We aim to achieve this through the development and application of an innovative approach leveraging controlled human infection models, novel platforms for helminth vaccine/vaccine antigen production, experimental animal models, and improved target discovery methodology applying state-of-the-art immunological profiling to identify correlates and signatures of protection. WORMVACS2.0 will advance scientific and clinical knowledge of host immunity in response to helminth infection, apply innovative and sustainable platform technologies tailored to the next generation of effective vaccines against helminth infections of global importance. The project will produce a diversified portfolio of hookworm and schistosome vaccine candidates ready for progressing to clinical testing and conduct a phase 1 clinical trial to advance an mRNA platform based schistosomiasis vaccine.

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.