Project: Identification of host regulators of tissue fibroproliferative pathology in schistosomiasis-diseased children in Africa

Acronym	MAQUISARD (Reference Number: TMA2016CDF-1571)
Duration	01/07/2018 - 30/06/2021
Project Topic	Intestinal schistosomiasis, specifically at the chronic stage, constitutes a health risk for 230 million people worldwide. The disease morbidity primarily results from the infected individuals poor ability to immunoregulate their response to parasite egg trapped in their liver. A progressive fibroproliferative response ensues leading to organ impairment, pathology and - when left untreated - death. The molecular mechanisms behind schistosomiasis-driven liver fibrosis remain elusive. The present project investigates by full genome mRNA sequencing of blood cells the factors differentially expressed by schistosomiasis-diseased school children that associate with the rapid onset and/or fast progression of liver fibrosis. Our approach reasons that a differential expression profile in schistosomiasis-diseased patients with comparable egg burden but different stage of advancement of the liver fibrosis should unveil host candidate factors that, by their sole differential expression, alter the progression of liver fibrosis in those patients. Proposed to take place at a highly endemic site for schistosomiasis in the locality of Yoro in Cameroon around the Mbam river, this project rooted in a cross-sectional study on 1000 school children specifically aims: 1. To define the knowledge, habits and practices of school children regarding schistosomiasis and the risk the disease represents in the area. This should be complemented by the egg-defined prevalence of the disease in relation to the individual habits. 2. To assess the advancement of liver fibropathology in the recruited children by ultrasonography and define comparative clusters of individuals with similar parasitological status but different fibropathological (liver) status. 3. To determine by next generation sequencing of children’s PBMCs-derived mRNA the differences in transcriptional profiles between children with fibrotic and non-fibrotic livers. Taken together, the different arms of our project should i) enable an updated mapping of the prevalence of schistosomiasis in the locality of Yoro, ii) unprecedentedly define an ultrasonographic profile of the liver pathology in children from this area reported highly endemic for hepato-intestinal schistosomiasis, iii) potentially unveil a unique library of host factors involved in the progression of pathological liver fibrosis in general and during schistosomiasis in particular, iv) and ultimately, build a clinical team and expertise around the fellow in South Africa and Cameroon for future work on clinical schistosomiasis focusing on the underlying basis of the disease mediated tissue fibropathology.
Network	EDCTP2
Call	Career Development Fellowships 2016

Project partner

Number	Name	Role	Country
1	University of Cape Town	Coordinator	South Africa