Neopterin is a cerebrospinal fluid marker for treatment outcome evaluation in patients affected by Trypanosoma brucei gambiense sleeping sickness

PLoS Negl Trop Dis. 2013;7(2):e2088. doi: 10.1371/journal.pntd.0002088. Epub 2013 Feb 28.

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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / cerebrospinal fluid*
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neopterin / cerebrospinal fluid*
  • Treatment Outcome
  • Trypanosoma brucei gambiense / pathogenicity*
  • Trypanosomiasis, African / drug therapy*
  • Young Adult

Substances

  • Biomarkers
  • Neopterin

Grants and funding

This work was supported by the Foundation for Innovative New Diagnostics (FIND) (http://www.finddiagnostics.org/) with funding from UBS Optimus Foundation (www.ubs.com/optimus/). D. Mumba Ngoyi received financial support from the Belgian Directorate General for International Cooperation. The Foundation for Innovative New Diagnostics (FIND) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.