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.

Susceptibility to Artemisinin-based combination therapies (ACTs) currently remains high among the African Plasmodium falciparum population, but resistant mutant has been detected recently. To mitigate the risk of resistance leading to a dramatic increase in malaria related mortality, more efficient ACTs need to be urgently explored for quick deployment in Africa. Artemether-lumefantrine (AL) is widely used and shows high efficacy and favourable safety in Africa but needs to be protected to increase its useful lifespan. Atovaquone-proguanil (AP) is highly efficacious, safe and resistant parasites are not circulating in any endemic area. AP targets multiple parasite stages -liver and blood in human host, and mosquito- through an independent mode of action, limiting the risk of cross-resistance with current ACTs. The aim of the project is to assess the efficacy of a triple-therapy associating artemether-lumefantrine (AL) and atovaquone-proguanil (AP) for the treatment of uncomplicated P. falciparum malaria in African children in a non-inferiority comparator-controlled trial. A phase III clinical trial will be conducted to compare safety and cure rate of a 3-day treatment course with AL+AP versus AL in 1,664 consenting 6 to 70 months children with uncomplicated malaria from Benin, Gabon, Ghana and Mali. The main outcome will be cure rate at day-42, excluding reinfections. Antimalarial pharmacokinetic parameters and post-treatment prophylactic efficacy will be estimated for the two treatments and compared. Sub-studies will look at transmission-blocking efficacy through membrane-feeding assays and gametocyte dynamics, drug resistance selection. By proofing that AL+AP has safety and cure rate similar to AL, this project will lead to important public health-level benefits by provision of a first candidate regimen to be deployed when ACT resistance spreads throughout Africa and by decreasing human to mosquito transmission.

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.