The last twenty years have seen the emergence or rediscovery of Buruli ulcer disease, a devastating skin infection caused by Mycobacterium ulcerans. This disease is characterized by progressive dermis infection causing extensive ulcerated lesions. Complications occur when bones, tendons are affected, and more than 50% of cases present incapacities after healing without additional care. It was described first in Uganda in the 60s and Central Africa, and is emerging in rural West Africa. M. ulcerans is an aquatic environmental mycobacterium, distantly related to M. tuberculosis and M. leprae. Its transmission route remains elusive, but the water environment has been shown to play a major role in its focal distribution. In Ghana and Ivory Coast, two countries most affected by this disease, national scale studies have shown that the regions most impacted by the disease were the same regions where dams had been constructed and where irrigated agriculture was most developed. It is therefore suspected that the emergence of Buruli ulcer is related to the profound environmental modifications undergone by rural African landscapes over the last decades. The aim of this project is to investigate the global correlations observed between human-made environmental changes such as dams, irrigation/agriculture, deforestation and endemic foci of this disease. The relationship between Buruli ulcer disease and environmental changes will be addressed in two historically endemic regions in different climates (equatorial and subtropical in Cameroon and Benin, respectively) and one newly discovered endemic focus close to a dam (in Cameroon). The program originality relies on the simultaneous collection of environmental, entomological, epidemiological and microbiological data from the same field study sites, their parallel processing by various methods and their final integration through mapping and modelling. Several disciplinary fields will interact and complement each other strongly during data collection and at every step of each task: environmental scientists specializing in ecology and geomatics will work closely with field botanists, entomologists and biologists, as well as epidemiologists, anthropologists and microbiologists. Most have a long history of collaborative work on Buruli ulcer attested by a large number of co-authored scientific publications. Finally, maps of M. ulcerans presence probability, as well as of M. ulcerans exposure risk will be produced at the regional scale and tentatively expanded at the national or supranational scale. Furthermore, understanding of the seasonal dynamics of M. ulcerans presence in the environment will allow recommendations to help population to prevent the disease in endemic regions and to limit the impact of environmental modifications on its spread. These space-time data on M. ulcerans presence and Buruli ulcer disease risk will be designed to be easily handled by public health actors, such as national Buruli ulcer control program officials or NGO personnel. This mapping will allow targeting of interventions such as active case detection or awareness campaigns to the areas identified as presenting the greatest risks. Feedback from Buruli ulcer diagnostic and treatment programs will allow model fine-tuning using field data.

More than a century ago, the Nobel prize-winning scientist Paul Erlich predicted that pathogens subjected to drugs would evolve resistance. In the ensuing years, this worrying prediction has been proven to be true for a large number of pathogen-drug combinations. Today, drug resistance is both a major public health issue and one of the best documented examples of evolution in real time. Drug resistance is a major issue in the control of malaria. The evolution of drug resistance by malaria parasites is accepted as inevitable by the World Health Organization: Plasmodium parasites have evolved resistance to all classes of anti-malarials that have gone into widespread use. New front-line drugs are urgently needed, but so are evidence-based resistance management strategies. For this, however, we need to understand the selective pressures involved in the evolution and spread of drug resistant mutations. The fate of drug resistant mutations depends on factors which we may be able to control, such as the rate and pattern of drug use. However, it also depends on factors over which we have no control, the most important of which is the biological cost that resistance imposes on the fitness of parasites. Drug resistance mutations are known to disrupt the parasite's metabolism, generating fitness costs. In drug-treated hosts these costs are largely compensated by the benefits conferred by the resistance. In untreated hosts, however, the magnitude of these costs will determine whether these mutations will persist and spread in the population. Current views about the costs of drug resistance are almost entirely based on data regarding parasitic infections in vertebrate hosts. The costs of resistance in the mosquito vector have either been ignored entirely or been given only cursory attention. The aim of this project is to investigate the biological costs of drug resistance in Plasmodium in both the vertebrate host and the mosquito vector. For this purpose we shall combine (i) an experimental approach using both artificially selected drug resistant strains of Plasmodium and an appropriate animal model (TASK 1), and field-collected drug resistant strains of P. falciparum, the aetiological agent of the most dangerous form of human malaria (TASK 2), (ii) an empirical approach in the field (Cameroun and Burkina Faso) that will allow us to compare the frequency of different drug resistant mutations in both humans and mosquitoes at dix different sites (TASK 3) and (iii) a theoretical modelling approach that will integrate data from the field (TASK 3) to make predictions about the evolution of drug resistance under different scenarios (different costs of drug resistance in mosquitoes and humans, TASK 4). The integration and feedback between these different approaches will provide the most complete picture to date of the transmission costs associated to drug resistance in Plasmodium and will potentially drastically alter predictions about the persistence and spread of drug resistance in the absence of treatment.

Determining how climate and global change are driving the geographical variation of vector-borne diseases (VBDs) transmission dynamics is essential to measure current and future risks and to effectively roll out innovative surveillance and vector control strategies aiming at reducing the burden for the most vulnerable populations, especially in Sub-Saharan Africa (SSA). IMPACTING aims to: 1) model the risk of VBDs spread under global change focusing on mosquitoes (malaria, dengue, chikungunya, yellow fever), tsetse (human African trypanosomiasis), blackflies (onchocerciasis) and ticks (Crimean-Congo haemorrhagic fever); 2) develop vector monitoring and pathogen diagnostic tools for improved surveillance; 3) develop robust pipelines to identify transmission blocking micro-organisms within vectors and define innovative VBD control strategies; 4) engage local rural and urban communities to co-develop solutions for VBD monitoring and control, bypassing current community level barriers; 5) develop a multi-VBD risk prediction dashboard to facilitate evidence-based policy making focused on innovative control strategies resilient to climate change. IMPACTING is built on a consortium of eight research institutes, three universities and one SME - based in Kenya, Cameroon, Mozambique, France and Portugal. It gathers expertise in social sciences, entomology, ecology, epidemiology, genomics, bioinformatics, modelling and software development, fostering an interdisciplinary approach. IMPACTING draws on extensive experience in other EU projects and strong fruitful collaborations to fill the gap in knowledge and innovation for VBDs and vector control in SSA and globally. IMPACTING aligns with the Africa CDC Strategic Plan 2023-27 and EU global health strategy. It focuses on improving health security through African leadership in research and innovation, combining digital and biological sciences, capacity building, and engagement with African communities and public health actors.

Urinary Tract Infections (UTIs) and antimicrobial resistance (AMR) pose significant global health threats, characterised by high incidence and mortality. However, in Sub-Saharan Africa (SSA), there is often a lack of accessible diagnostics to guide proper treatment and therapy monitoring. Our objectives are as follows: (1) Develop and validate a two-tier diagnostic toolbox: (a) Implement a Lateral Flow Test (LFT) for detecting urinary biomarkers at primary care for triage; (b) Deploy a compact, portable Point-of-Care (POC) instrument for secondary care (hospitals, clinics), integrating pathogen detection via isothermal nucleic acid amplification and host-response biomarker quantification for evidence-based therapy and antibiotic prescription; (c) Introduce novel (self)-sampling cards for transport without the need for a cold chain; (d) Establish a digital health platform for clinical decision support. (2) Evaluate the toolbox's field deployability, acceptance, usability, and integration into clinical practice. (3) Maximise the adoption, implementation, and accessibility of the proposed diagnostic toolbox. (4) Prepare for post-project regulatory approval and market launch. (5) Enhance capacity building and surveillance structures through local manufacturing transfer and improvement of the supply chain and logistics. We will recruit diverse patient groups, including under-represented segments of society, from various African settings to ensure the broad applicability, sustainability, and customisability of our solutions. This project is expected to have a significant impact, improving the quality of UTI/AMR diagnostics, reducing unnecessary antibiotic use, preventing resistance, strengthening health systems and their response to epidemics, and increasing accessibility and quality of diagnostics through interdisciplinary and robust industrial collaboration.

Leprosy (Hansen disease) and Buruli ulcer are among the devastating skin neglected tropical diseases (Skin NTDs) prevalent in sub-Saharan Africa that cause progressive and permanent disabilities, exposing the patients and their families to discrimination, social stigma, and economic burden, adding complex challenges to communities already exposed to extreme inequality. Considering the needs of the most affected populations, children and people living in rural remote areas, current treatments are suboptimal in their complexity and length. Treating leprosy requires multiple drugs administered for 6 to 12 months. Buruli ulcer treatment requires 3 pills daily at different hours for two months, and lesion healing can take up to 12 months. Both treatments are associated with significant side effects (skin discoloration from clofazimine, exacerbating the stigma that leprosy patients face, and potentially fatal hypersensitivity to dapsone). This proposal aims to transform the treatment of Buruli ulcer and leprosy using the novel compound telacebec. Telacebec has demonstrated profound activity against Mycobacterium ulcerans and Mycobacterium leprae, the causative agents of Buruli ulcer and leprosy, respectively, whose evolutionary biology has rendered them hypersusceptible to killing by telacebec. We propose to conduct two clinical trials with telacebec-based treatment regimens that will cure Buruli ulcer and leprosy with fewer drugs, shorter duration, and fewer side effects than current therapy. We will perform this work through an integrated, multidisciplinary consortium of experts with broad experience in drug development, therapeutic delivery, community engagement, stakeholder participation, policy implementation, and capacity building to achieve equitable access to a new standard of care for these diseases.