title: Neopterin is a cerebrospinal fluid marker for treatment outcome evaluation in patients affected by Trypanosoma brucei gambiense sleeping sickness.
abstract: BACKGROUND
  Post-therapeutic follow-up is essential to confirm cure and to detect early treatment failures in patients affected by sleeping sickness (HAT). Current methods, based on finding of parasites in blood and cerebrospinal fluid (CSF) and counting of white blood cells (WBC) in CSF, are imperfect. New markers for treatment outcome evaluation are needed. We hypothesized that alternative CSF markers, able to diagnose the meningo-encephalitic stage of the disease, could also be useful for the evaluation of treatment outcome.
  
  
  RESULTS
  Cerebrospinal fluid from patients affected by Trypanosoma brucei gambiense HAT and followed for two years after treatment was investigated. The population comprised stage 2 (S2) patients either cured or experiencing treatment failure during the follow-up. IgM, neopterin, B2MG, MMP-9, ICAM-1, VCAM-1, CXCL10 and CXCL13 were first screened on a small number of HAT patients (n = 97). Neopterin and CXCL13 showed the highest accuracy in discriminating between S2 cured and S2 relapsed patients (AUC 99% and 94%, respectively). When verified on a larger cohort (n = 242), neopterin resulted to be the most efficient predictor of outcome. High levels of this molecule before treatment were already associated with an increased risk of treatment failure. At six months after treatment, neopterin discriminated between cured and relapsed S2 patients with 87% specificity and 92% sensitivity, showing a higher accuracy than white blood cell numbers.
  
  
  CONCLUSIONS
  In the present study, neopterin was highlighted as a useful marker for the evaluation of the post-therapeutic outcome in patients suffering from sleeping sickness. Detectable levels of this marker in the CSF have the potential to shorten the follow-up for HAT patients to six months after the end of the treatment.
authors.affiliation: Translational Biomarker Group, Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Tiberti
authors.forename: Veerle
authors.initials: V
authors.lastname: Lejon
authors.forename: Alexandre
authors.initials: A
authors.lastname: Hainard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Courtioux
authors.forename: Xavier
authors.initials: X
authors.lastname: Robin
authors.forename: Natacha
authors.initials: N
authors.lastname: Turck
authors.forename: Krister
authors.initials: K
authors.lastname: Kristensson
authors.forename: Enock
authors.initials: E
authors.lastname: Matovu
authors.forename: John Charles
authors.initials: JC
authors.lastname: Enyaru
authors.forename: Dieudonné
authors.initials: D
authors.lastname: Mumba Ngoyi
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Krishna
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bisser
authors.forename: Joseph Mathu
authors.initials: JM
authors.lastname: Ndung'u
authors.forename: Philippe
authors.initials: P
authors.lastname: Büscher
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid*; D016896:Treatment Outcome; D014347:Trypanosoma brucei gambiense / Q000472:pathogenicity*; D014353:Trypanosomiasis, African / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019798:Neopterin