Brambilla Carnielli Trindade, Juliana, Monti-Rocha, Renata, Costa, Dorcas Lamounier. et al. (7 more authors) (2019) Natural Resistance of Leishmania infantum to Miltefosine Contributes to the Low Efficacy in the Treatment of Visceral Leishmaniasis in Brazil. American journal of tropical medicine and hygiene. pp. 789-794. ISSN 1476-1645
Abstract
In India visceral leishmaniasis (VL) caused by Leishmania donovani has been successfully treated with miltefosine with a cure rate of > 90%. To assess the efficacy and safety of oral miltefosine in L. infantum-causing Brazilian VL patients, a phase II, open-label, dose-escalation study of oral miltefosine was conducted in children (ages 2-12) and adolescent-adults (ages 13-60). Definitive cure was assessed at a 6 month follow-up visit. The cure rate was only 42% (6 out of 14 patients) with the recommended 28 days of therapy and 68% (19 out of 28 patients) with an extended treatment of 42 days. The in vitro miltefosine susceptibility profile of intracellular amastigote stages of the pre-treatment isolates, from cured and relapsed patients, showed a positive correlation with clinical outcome. The IC50 mean (SEM) of eventual cures was 5.1 (0.4) µM whereas that of eventual failures was 12.8 (1.9) µM (P = 0.0002). An IC50 below or above 8.0 µM predicts cure or failure, respectively with 82% sensitivity and 100% specificity. The finding of L. infantum 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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 by The American Society of Tropical Medicine and Hygiene. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Centre for Immunology and Infection (CII) (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 07 Jun 2019 07:50 |
Last Modified: | 16 Dec 2024 00:10 |
Published Version: | https://doi.org/10.4269/ajtmh.18-0949 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.4269/ajtmh.18-0949 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:147054 |