Metabolomics Identifies Multiple Candidate Biomarkers to Diagnose and Stage Human African Trypanosomiasis.

摘要: Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing disease and stage (stage 1 defined by parasites being present in blood lymphatics whilst 2, are found beyond blood-brain barrier cerebrospinal fluid (CSF)). Currently, staging relies upon detecting very low number or elevated white cell numbers CSF. Improved desirable, as elimination need lumbar puncture. Here we use metabolomics to probe samples CSF, plasma urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different stages. Urine provided no robust markers indicative infection due inherent variability concentrations. Biomarkers CSF were able distinguish advanced 2 absolute specificity. Eleven metabolites clearly distinguished most two these (neopterin 5-hydroxytryptophan) showed 100% specificity sensitivity between our samples. Neopterin an inflammatory biomarker previously shown but not patients. 5-hydroxytryptophan important metabolite serotonin synthetic pathway, key pathway determining somnolence, thus offering a possible link eponymous symptoms “sleeping sickness”. Plasma also yielded several biomarkers presence (87% 95% specificity) (92% 81% specificity). A logistic regression model including clear separation either indeed diseased (both stages) versus control.