Metabolic plasma signatures and improved Schistosoma mansoni diagnosis of children from endemic areas in Cameroon: Identifying infection and morbidity markers - A University of Glasgow-IMPM collaborative study

Funder: Royal Society
PI: Poppy Lamberton Co-I: Dr Justin Nono Komguep

Summary

Over 240 million people are infected with schistosomiasis, with >90% of these in sub-Saharan Africa. Schistosoma mansoni causes intestinal schistosomiasis, with symptoms ranging from anaemia, reduced physical and cognitive development to liver fibrosis and death. Control strategies focus on praziquantel mass drug administration, but uptake rarely reaches the World Health Organization target of 75% coverage. Efficacy of praziquantel, is not 100% and treatment does not prevent reinfection. In endemic areas, chronic infections and repeated re-infections lead to widespread severe disease. Tissue fibroproliferative pathology, caused by chronic infections, is not fully reversed by praziquantel treatment, many individuals are left with persistent impairment of affected organ function. Development of alternative therapeutic measures that minimise reinfection and reduce fibroproliferative pathology would reduce disease burden. A detailed knowledge of the molecular basis of schistosomiasis infection susceptibility and tissue pathology is crucial.

Infections with helminth parasites, including schistosomes, are affected by, and alter, host metabolism and metabolites. High-throughput identification of metabolites in biological fluids, provides extensive data aiding understanding of disease mechanisms and informing biomarker discovery by elucidating infection frameworks and associated pathology.

Objectives

The overall objective of our study is to establish a plasma metabolite profile associated with S. mansoni infection and liver fibrosis, controlling for egg excretion as a measure of worm burden, generating a comprehensive database of druggable transmission-blocking/infection-specific and fibrosis-associated metabolites. Instead of only testing targets identified in model systems, we have the potential to identify novel metabolites, for future collaborative investigations into metabolite profiles predictive of schistosomiasis infection and morbidity. We also aim to quantify the association between adult worm burden and egg excretion and how that is correlated to liver fibrosis and fibrosis-associated metabolites.