Macrophage Activation Marker Neopterin: A Candidate Biomarker for Treatment Response and Relapse in Visceral Leishmaniasis

• Published in: Frontiers in cellular and infection microbiology Vol. 8; p. 181
• Main Authors: Kip, Anke E, Wasunna, Monique, Alves, Fabiana, Schellens, Jan H M, Beijnen, Jos H, Musa, Ahmed M, Khalil, Eltahir A G, Dorlo, Thomas P C
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01-06-2018
• Subjects: biomarker; kala-azar; liposomal amphotericin B; macrophage activation; Microbiology; miltefosine; neopterin; pharmacodynamics; visceral leishmaniasis; liposomal amphotericin B; pharmacodynamics; kala-azar; macrophage activation; miltefosine; biomarker; neopterin; visceral leishmaniasis
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2018.00181

The
parasite resides and replicates within host macrophages during visceral leishmaniasis (VL). This study aimed to evaluate neopterin, a marker of macrophage activation, as possible pharmacodynamic biomarker to monitor VL treatment response and to predict long-term clinical relapse of VL. Following informed consent, 497 plasma samples were collected from East-African VL patients receiving a 28-day miltefosine monotherapy (48 patients) or 11-day combination therapy of miltefosine and liposomal amphotericin B (L-AMB, 48 patients). Neopterin was quantified with ELISA. Values are reported as median (inter-quartile range). Baseline neopterin concentrations were elevated in all VL patients at 98.8 (63.9-135) nmol/L compared to reported levels for healthy controls (<10 nmol/L). During the first treatment week, concentrations remained stable in monotherapy patients (
= 0.807), but decreased two-fold compared to baseline in the combination therapy patients (
< 0.01). In the combination therapy arm, neopterin concentrations increased significantly 1 day after L-AMB infusion compared to baseline for cured patients [137 (98.5-197) nmol/L,
< 0.01], but not for relapsing patients [84.4 (68.9-106) nmol/L,
= 0.96]. The neopterin parameter with the highest predictive power for VL relapse was a higher than 8% neopterin concentration increase between end of treatment and day 60 follow-up (ROC AUC 0.84), with a 93% sensitivity and 65% specificity. In conclusion, the identified neopterin parameter could be a potentially useful surrogate endpoint to identify patients in clinical trials at risk of relapse earlier during follow-up, possibly in a panel of biomarkers to increase its specificity.