Metabolomics Identifies multiple candidate biomarkers to diagnose and stage human African trypanosomiasis

Vincent, I. M. , Daly, R. , Courtioux, B., Cattanach, A. M., Biéler, S., Ndung’u, J. M., Bisser, S. and Barrett, M. P. (2016) Metabolomics Identifies multiple candidate biomarkers to diagnose and stage human African trypanosomiasis. PLoS Neglected Tropical Diseases, 10(12), e0005140. (doi: 10.1371/journal.pntd.0005140) (PMID:27941966) (PMCID:PMC5152828)

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

Item Type:Articles
Glasgow Author(s) Enlighten ID:Vincent, Dr Isabel and Cattanach, Dr Amy and Barrett, Professor Michael and Daly, Dr Ronan
Authors: Vincent, I. M., Daly, R., Courtioux, B., Cattanach, A. M., Biéler, S., Ndung’u, J. M., Bisser, S., and Barrett, M. P.
Subjects:?? Research Article ??
?? Biology and life sciences ??
?? Medicine and health sciences ??
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2016 Vincent et al.
First Published:First published in PLoS Neglected Tropical Diseases 10(12): e005140
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOME)104111/Z/14/Z &III - PARASITOLOGY
623593Institutional Strategic Support Fund (ISSF)Anna DominiczakWellcome Trust (WELLCOME)105614/Z/14/ZRI CARDIOVASCULAR & MEDICAL SCIENCES