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Macrophage Activation Marker Neopterin: A Candidate Biomarker for Treatment Response and Relapse in Visceral Leishmaniasis.
- Source :
- Frontiers in Cellular & Infection Microbiology; 6/1/2018, Vol. 8, pN.PAG-N.PAG, 8p
- Publication Year :
- 2018
-
Abstract
- The <italic>Leishmania</italic> 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 (<italic>p</italic> = 0.807), but decreased two-fold compared to baseline in the combination therapy patients (<italic>p</italic> < 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, <italic>p</italic> < 0.01], but not for relapsing patients [84.4 (68.9–106) nmol/L, <italic>p</italic> = 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 22352988
- Volume :
- 8
- Database :
- Complementary Index
- Journal :
- Frontiers in Cellular & Infection Microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 129967297
- Full Text :
- https://doi.org/10.3389/fcimb.2018.00181