Neopterin Is a Cerebrospinal Fluid Marker for Treatment Outcome Evaluation in Patients Affected by Trypanosoma brucei gambiense Sleeping Sickness
PLoS Neglected Tropical Diseases
Translational Biomarker Group, Department of Human Protein Sciences, University of Geneva, Geneva, Switzerland; Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium; Institut National de la Santé et de la Recherche Médicale (INSERM), UMR1094, Tropical Neuroepidemiology, Limoges, France; Institute of Neuroepidemiology and Tropical Neurology, School of Medicine, CNRS FR 3503 GEIST, University of Limoges, Limoges, France; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Veterinary Parasitology and Microbiology, School of Veterinary Medicine, Makerere University, Kampala, Uganda; Department of Biochemistry, College of Natural Sciences, Makerere University, Kampala, Uganda; Department of Parasitology, Institut National de Recherche Biomédicale, Kinshasa, Congo; Centre for Infection, Division of Cellular and Molecular Medicine, St. George's, University of London, London, United Kingdom; Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland
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. © 2013 Tiberti et al.
beta 2 microglobulin; CXCL13 chemokine; gamma interferon inducible protein 10; gelatinase B; immunoglobulin M; intercellular adhesion molecule 1; neopterin; vascular cell adhesion molecule 1; adult; African trypanosomiasis; article; blood analysis; cerebrospinal fluid analysis; cohort analysis; diagnostic test accuracy study; ELISA kit; female; follow up; human; leukocyte count; major clinical study; male; receiver operating characteristic; relapse; risk factor; sensitivity and specificity; treatment failure; treatment outcome; Trypanosoma; Adult; Biological Markers; Drug Monitoring; Female; Humans; Male; Middle Aged; Neopterin; Treatment Outcome; Trypanosoma brucei gambiense; Trypanosomiasis, African; Young Adult