Authors
J M Sternberg2; S Lamour1; P G Kennedy 1 Imperial College; 2 University of Aberdeen; 3 University of Glasgow Discussion
African trypanosome infections progress from an early haemolymphatic stage to a late meningoencephalitic stage. So much is well known. The transition between these stages may be seen from a biological perspective (eg anatomical compartments and kinetics of brain invasion) and from a therapeutic imperative (as the late stage requires drug treatment with serious toxicity and/or logistic issues). In the clinic, stage determination is based on the analysis of cerebrospinal fluid (CSF), with the main diagnostic criterion being pleiocytosis. However, it is now becoming apparent that current clinical staging criteria may not be consistent either with biological aspects of stage progression, nor therapeutic cut-offs. We describe the analysis of CSF samples from HAT patients using metabolomic approaches, to discover whether small metabolites may be diagnostic for CNS invasion by trypanosomes and the relationship of metabolomics profile to current staging criteria. Metabolites of tryptophan oxidation indicate the onset of parasite-inducted inflammatory processes in the brain already in conventionally diagnosed early stage patients. Meanwhile, 3-hydroxybutyrate, alanine, mannose and urea were