Leishmaniasis

The latter is performed in close collaboration with the Unit of Molecular Parasitology within the Department of Biomedical Sciences, that leads

1. the improvement of genomic surveillance tools (e.g. direct parasite genome sequencing in host tissues),

2. their application for clinical and epidemiological purposes (among others, source tracing, analysing the evolution of outbreaks, identifying new variants and relevant traits like virulence and drug response, studying co-evolution with endosymbionts and detecting and measuring the impact of parasite sexual recombination),

3. their implementation in an integrated platform, highly relevant in the post-elimination context.

The research portfolio currently also includes the biology of viscerotropic and dermotropic Leishmania, with a specific focus on the understanding of the parasite’s adaption and resilience to different environments encountered during their life cycle and/or exposure to therapeutic or prophylactic agents. Research topics include genome plasticity and instability, quiescence and persistence, drug resistance and drug tolerance. These mechanisms are common in other Trypanosomatids, and will also provide technological innovations in disease control products, more specifically guiding R&D for a new generation of anti-Leishmania compounds for instance to counter quiescence.

In analogy, the Unit of Clinical Immunology (CIU) within the Department of Clinical Sciences is geared to provide a complementary (and spatially resolved) understanding of a protective host immune response to the parasite and its immune escape mechanisms to ensure intracellular survival (e.g. dysregulated antigen presentation) directly in patient samples. Further capitalising on surveillance efforts of the other units, CIU aims to roll out a first-in-its-kind T-cell epitope mapping of immunogenic Leishmania peptides by means of an artificial-intelligence-facilitated framework that can accurately inform antigen selection in vaccine development. In a more translational pathway, the CIU strives to apply generated knowledge in the development of improved host-based diagnostics, test-of-cure, or biomarker assays that are currently lacking to address the WHO sustainable development goals or elimination goals for leishmaniasis.

The highest burden of visceral leishmaniasis (VL) due to L. donovani has shifted to East Africa, where for the last twelve years, the Unit of Neglected Tropical Diseases within the Department of Clinical Sciences (in close collaboration with the above units) has worked on clinical and laboratory research of VL and the prevalent coinfection with HIV, which hinders elimination programmes as a group of potential superspreaders. Clinical studies range from prediction of VL, improved combination treatment and secondary prophylaxis. The NTD unit has engaged in several grant proposals and prospective cohort studies to improve patient detection and surveillance, to identify prognostic markers for VL-mortality, and to develop novel diagnostic algorithms at health-centre level. Following the recent Nairobi Declaration where East-African countries committed to the elimination of VL by 2030, the NTD unit aspires to levy the common ITM expertise described here to tackle key hurdles to accommodate elimination programmes in East-Africa. In a similar fashion, the NTD unit conducts studies on improved diagnostics, treatment, transmission dynamics and surveillance for the more neglected form of cutaneous leishmaniasis integrated in horizontal skin NTDs programmes (e.g. decentralised diagnosis and treatment of CL in a holistic skin NTD package).

The Unit of Entomology within the Department of Biomedical Sciences focuses on the sand fly vector aiming at understanding its ecology and its role in transmission of Leishmania spp. This research should define the role of vector control in the VL elimination in Asia (Nepal and Bangladesh). Further, the unit looks into novel vector control methods for Zoonotic Cutaneous Leishmaniasis (ZCL). In the context of ZCL the Unit also disentangled the basic transmission cycle of Leishmania in Morocco, a prerequisite to improve targeted vector control. Through VectorNet, the unit contributes to mapping the distribution of the sand fly vector and biocide resistance in Europe and neighbouring countries.

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