期刊
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2018.00181
关键词
neopterin; biomarker; visceral leishmaniasis; kala-azar; macrophage activation; pharmacodynamics; miltefosine; liposomal amphotericin B
资金
- Medecins Sans Frontieres International
- Medicor Foundation
- Department for International Development (DFID), UK
- Dutch Ministry of Foreign Affairs (DGIS), the Netherlands
- Federal Ministry of Education and Research (BMBF) through KfW, Germany
- Swiss Agency for Development and Cooperation (DDC- SDC), Switzerland
- Netherlands Organization for Scientific Research (ZonMw/NWO) [91617140]
The Leishmania 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 (p = 0.807), but decreased two-fold compared to baseline in the combination therapy patients (p < 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, p < 0.01], but not for relapsing patients [84.4 (68.9-106) nmol/L, p = 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.
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