Periodic Reporting for period 2 - LeiSHield-MATI (A multi-disciplinary international effort to identify clinical, molecular and social factors impacting cutaneous leishmaniasis) Reporting period: 2020-04-01 to 2023-09-30 Summary of the context and overall objectives of the project Leishmania causes devastating human diseases – leishmaniases - representing an important public health problem in the Mediterranean basin and declared as emerging diseases in the EU due to climate change and population displacement. The LeiSHield-MATI consortium investigates in an integrative fashion the complex parasite-vector-host interplay in cutaneous leishmaniasis affecting Morocco, Algeria, Tunisia, and Iran (MATI), using field isolates and hu-man clinical samples. The ultimate goal of our project is to identify genetic factors selected during natural infection and to understand how the complex parasite-vector-animal interaction impacts clinical outcome in infected patients. This goal will be achieved through a highly ambitious se-condment plan between all partners, and the organization of courses and workshops to train the next generation of scientists generating a long-term impact on the research capacities in endemic areas. Capitalizing on complementary infrastructures of its EU, African and Asian partners and their expertise in molecular parasitology, epidemiology, systems level analyses, bioinformatics, computational biology, immunology, dermatology, field studies, and public health, our project will drive important innovation in clinical research, strengthen capacities in disease endemic regions, inform authorities on control measures, and raise awareness in all partner countries on this emerg-ing EU public health problem.The LeiSHield-MATI staff exchange project has been a very important instrument to train the next generation of scientists from Leishmania endemic countries as judged by the over 257,18 person months of secondments carried out by 106 researchers and the numerous workshops and teaching courses that transferred both hard and soft skills. Through these exchanges, our consortium was driving major scientific discovery and technology innovation, which has been validated through publications on Leishmania genomic adaptation, direct tissue sequencing, rodent infection, sand fly species determination, CL diagnostics, and the skin immune response to infection. The project not only synergized prior existing collaborations but was a major source of new collaboration that will give the project a long-lasting impact on scientific cooperation across disease-endemic regions. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The major goal of LeiSHield-MATI is to establish a novel collaborative platform across the EU and CL-endemic countries in Africa and Asia. We attained this goal through the following Specific Objectives: - Objective 1: Standardize procedures for sampling, species determination, and HTseq analysesThe timely and efficient fulfillment of Objective 1 set the stage for the successful execution of the objectives below using standardized conditions applied across the entire consortium, including a common bio-informatics pipeline published in Nucleic Acid Research (Späth and Bussotti 2022), which allowed for cross-comparison of results between teams. - Objective 2: Correlate CL clinical manifestations to parasite genomic diversity and Leishmania LRV infection It allowed major discoveries across the MATI region with respect to parasite genetic heterogeneity, hybridization, and evolution in the field, why are subject of 5 manuscripts at different stages of the publication process, including one published in Microbial Genomics (Bussotti et al., 2020), 2 pre-published on bioRxiv (Talimi et al, in revision in Microbial Genomics; Bruno et al., submitted), and 2 manuscripts in preparation on direct tissue sequencing of Moroccan L. tropica isolates and the geographic adaptation of L. tropica isolates from Iran. - Objective 3 & 4: Identify common and region-specific bio-markers associated with the different forms of CL & Assess genetic diversity, recombination, and mixed infection in Leishmania isolates from natural sand fly infections and reservoir animals We established and successfully applied highly innovative approaches for Sand fly species determination based on DNA-barcodes and MALI-TOF analysis, which have been validated through publications in Transbound Emerg Disease (Mhaidi et al., 2022), Vet Parasitol Reg Stud Reports (Messahel et al, 2022) and PLoS Negl Trop Dis. (Benallal et al., 2022). - Objective 5 & 6: Characterize the genetic heterogeneity of the natural sand fly population and their susceptibility to Leishmania infection using a phylogenomic approach & Identify the natural rodent reservoir for CL to understand the local transmission cycles We allowed important new insight into the transmission cycle of various Leishmania species in Algeria as documented by publications in J Med Entomol. (El Kacem et al., 2023), Int J Parasitol Parasites Wildl. (Benallal et al., 2023), Pathogens 2023 (Sadlova et al., 2023).- Objective 7: Define surrogate marker(s) of human protection applying a systems-immunology approach on clinical samplesWe allowed unprecedented insight into the local immune response to cutaneous Leishmania infection and (i) uncovered local immune surrogate signatures of CL caused by L. tropica (Taslimi et al, Cytokine 2020; Taslimi et al., Heliyon 2023; Masoudzadeh et al, Scientific Reports 2020), (ii) identified differential immune-related transcripts in blood of CL patients with active lesions and CL healed individuals (Bahrami et al., Molecular Immunology 2022), and revealed a number of putative transcript surrogate markers (submitted to journal “Molecular Immunology" for publication).- Objective 8 & 10: Investigate CL lesion evolution and its social and psychological impact in endemic regions & Communicate and disseminate results stemmed from the project to policy makers and industry in order to create new incentives for the development of novel diagnostic and therapeutic toolsThese Objectives could not be achieved due to ‘force majeure’ which were outside the control of the consortium management. - Objective 9: Coordinate knowledge transfer actions inside and outside of LeiSHield-MATI consortium to ensure optimal staff exchanges, build strong sustainable collaborations, promote self-sustainability and further develop the careers of participating staffOur staff exchange program has played a crucial role in achieving the overarching goal of the LeiSHield-MATI project, as it strengthened collaborations on the long-term, fostered career development and thus allowed the emergence of future leaders in regional scientific research, and ensured the efficient transfer of knowledge in the field of leishmaniasis. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) LeiSHield-MATI boosted international collaboration and skill development. Emphasizing early-career researchers' involvement, 38 joined secondments. Tailored events amplified their expertise, benefitting wider audiences. Overall, 106 researchers engaged for 257.18 months.Secondees sharpened lab and soft skills, transferring knowledge via specialized sessions:- Rodent Reservoir Hosts Conference- Biosafety and Biosecurity Workshop- Scientific Outreach TrainingThese examples highlight diverse project offerings, fostering technical and interpersonal growth.Consortium meetings focused on sustaining LeiSHield-MATI post-funding. The final symposium sparked discussions on securing future funding. LOGO Leishield-Mati
