Human African trypanosomiasis (HAT) is a neglected parasitic disease affecting rural communities in sub-Saharan Africa. The disease progresses from a first heamolymphatic stage to a second meningo-encephalitic stage, when trypanosome parasites penetrate into the central nervous system. In order to properly and safely treat patients, new tools for a correct stage determination are strongly needed. In this project we investigated the cerebrospinal fluid of HAT patients using different approaches, including proteomics and hypothesis driven discovery. We identified promising staging markers to stratify patients suffering either from the acute or the chronic form of HAT. Among the most promising molecules, we further validated on a multi-centric cohort the value of neopterin as HAT marker for stage determination and treatment outcome evaluation for T.b.gambiense HAT. This highly accurate HAT marker has the potential to be translated into a rapid field test to ameliorate patients' management and to help in controlling the disease.