Volume 101, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



In India, visceral leishmaniasis (VL) caused by has been successfully treated with miltefosine with a cure rate of > 90%. To assess the efficacy and safety of oral miltefosine against Brazilian VL, which is caused by , a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (aged 2–12 years) and adolescent-adults (aged 13–60 years). Definitive cure was assessed at a 6-month follow-up visit. The cure rate was only 42% (6 of 14 patients) with a recommended treatment of 28 days and 68% (19 of 28 patients) with an extended treatment of 42 days. The in vitro miltefosine susceptibility profile of intracellular amastigote stages of the pretreatment isolates, from cured and relapsed patients, showed a positive correlation with the clinical outcome. The IC mean (SEM) of eventual cures was 5.1 (0.4) µM, whereas that of eventual failures was 12.8 (1.9) µM ( = 0.0002). An IC above 8.0 µM predicts failure with 82% sensitivity and 100% specificity. The finding of amastigotes resistant to miltefosine in isolates from patients who eventually failed treatment strongly suggests natural resistance to this drug, as miltefosine had never been used in Brazil before this trial was carried out.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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  • Received : 28 Nov 2018
  • Accepted : 03 Jun 2019
  • Published online : 19 Aug 2019

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