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Macrophage Activation Marker Neopterin : A Candidate Biomarker for Treatment Response and Relapse in Visceral Leishmaniasis.
- Kip, Anke E (author)
- Wasunna, Monique (author)
- Alves, Fabiana (author)
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- Schellens, Jan H M (author)
- Beijnen, Jos H (author)
- Musa, Ahmed M (author)
- Khalil, Eltahir A G (author)
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- (creator_code:org_t)
- 2018-06-01
- 2018
- English.
- In: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media SA. - 2235-2988. ; 8, s. 181-
- Journal article (peer-reviewed)
Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- biomarker
- kala-azar
- liposomal amphotericin B
- macrophage activation
- miltefosine
- neopterin
- pharmacodynamics
- visceral leishmaniasis
Publication and Content Type
- ref (subject category)
- art (subject category)
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