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Project Topic
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Context and overall objectives of the actionPost kala azar dermal leishmaniasis (PKDL) is a skin disease that follows treatment for visceral leishmaniasis (VL; kala azar). In addition to its impact on patients, PKDL is widely considered a threat to the elimination of VL. The incidence, clinical presentation and chronicity of PKDL varies geographically. In Sudan nearly a third of cured VL patients develop PKDL within 12 months. Approximately eighty percent of these cases self-cure after several months, but drug toxicity (e.g. nephrotoxicity) precludes early treatment. The stigma of PKDL significantly reduces quality of life, particularly for children and women. Whilst safer / shorter treatment options are desirable, prevention of PKDL represents the most clinically beneficial solution. PKDL is an immunological disease involving a dysregulation of innate and /or acquired immunity that allows parasite persistence in the skin and sustained inflammation. Recently, University of York (UoY) has developed a “third generation” leishmaniasis vaccine (ChAd63-KH) that can stimulate immune responses that are known to be defective in PKDL patients, leading to the hypothesis that inducing these responses by vaccination will have therapeutic benefit. PREV_PKDL is a collaborative project funded by the European & Developing Countries Clinical Trials Partnership (EDCTP2) Programme supported by the European Union. The project is the joint effort of leading European and African experts with proven track records in research and development of products against leishmaniasis.Specific objectives of the PREV_PKDL project are to: prepare and start the conduct a Phase II Randomised Controlled Trial to evaluate safety and efficacy of ChAd63-KH for prevention of PKDL in cured VL patients in Sudan up to an interim safety evaluation continue the conduct of the Phase II Trial following DSMB and sponsor approval conduct an in-depth analysis of the immune set point at cure from VL in patient cohorts from Ethiopia, Kenya, Sudan and Uganda provide novel mechanistic insights into natural history of VL / PKDL and biomarkers of PKDL development through multi-dimensional, multiparameter phenotyping enhance immunology research capacity in the East African Region (EAR), encouraging new North-South and South-South collaboration;Work performed from the beginning of the project and main results achieved so far The preparation of the phase IIb clinical trial at IEND, Sudan, is ongoing and the clinical dossier is planned to be submitted to the Sudanese Ethics Committee (EC) and Regulatory Authorities (RAs) by quarter 3 of 2019.The tender procedure for the procurement of the five flow cytometers was published by UoY and the supplier of the machines was selected (Beckham Coulter). The five machines will be first delivered to UoY to allow a hands-on training of the flow cytometry managers that have been appointed at each African site for the PREV_PKDL project and will subsequently be delivered to their final destinations. Progress beyond the state of the art and expected potential impactThe leishmaniases are still some of the world’s most neglected diseases, affecting largely the poorest of the poor, mainly in developing countries, and present a severe barrier to socio-economic development. PREV_PKDL will generate high quality new data on safety and efficacy of a new medical product (ChAd63-KH), develop sustainable clinical research capacity for long term benefit (including upgrading of laboratory facilities and generation of sustainable expertise and leadership), encourage greater coordination of research across nations (via LEAP) and facilitate networking and equal partnerships (including North-South and South-South). Through links to other projects we will help build regional capacity in ethics and governance.In addition, this development programme will advance leishmaniasis vaccine research in the broader context, providing for African leadership of research with global reach. The capacity developed for flow cytometry will underpin clinical research and product development for other PRNDs.PREV_PKDL directly addresses Sustainable Development Goal (SDG) 3 (Good Health and Well-being), as well as SDGs 1 (No Poverty), 5 (Gender Equality), 9 (Industry, Innovation and Infrastructure), 10 (Reduced Inequalities) and 17 (Partnership for the Goals).Project website: www.prevpkdl.eu
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