Lumefantrine attenuates Plasmodium falciparum artemisinin resistance during the early ring stage.

Autor:	Kümpornsin K; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK., Loesbanluechai D; Genomics and Evolutionary Medicine Unit (GEM), Centre of Excellence in Malaria Research, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Molecular Medicine Program, Multidisciplinary Unit, Faculty of Science, Mahidol University, Bangkok, Thailand., de Cozar C; Global Health. GlaxoSmithKline I&D, Tres Cantos, Madrid, Spain., Kotanan N; Genomics and Evolutionary Medicine Unit (GEM), Centre of Excellence in Malaria Research, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Chotivanich K; Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., White NJ; Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Churchill Hospital, Oxford, United Kingdom., Wilairat P; Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand., Gomez-Lorenzo MG; Global Health. GlaxoSmithKline I&D, Tres Cantos, Madrid, Spain., Gamo FJ; Global Health. GlaxoSmithKline I&D, Tres Cantos, Madrid, Spain., Sanz LM; Global Health. GlaxoSmithKline I&D, Tres Cantos, Madrid, Spain., Lee MCS; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. Electronic address: ml31@sanger.ac.uk., Chookajorn T; Genomics and Evolutionary Medicine Unit (GEM), Centre of Excellence in Malaria Research, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: thanat.cho@mahidol.edu.
Jazyk:	angličtina
Zdroj:	International journal for parasitology. Drugs and drug resistance [Int J Parasitol Drugs Drug Resist] 2021 Dec; Vol. 17, pp. 186-190. Date of Electronic Publication: 2021 Oct 02.
DOI:	10.1016/j.ijpddr.2021.09.005
Abstrakt:	Emerging artemisinin resistance in Plasmodium falciparum malaria has the potential to become a global public health crisis. In Southeast Asia, this phenomenon clinically manifests in the form of delayed parasite clearance following artemisinin treatment. Reduced artemisinin susceptibility is limited to the early ring stage window, which is sufficient to allow parasites to survive the short half-life of artemisinin exposure. A screen of known clinically-implemented antimalarial drugs was performed to identify a drug capable of enhancing the killing activity of artemisinins during this critical resistance window. As a result, lumefantrine was found to increase the killing activity of artemisinin against an artemisinin-resistant clinical isolate harboring the C580Y kelch13 mutation. Isobologram analysis revealed synergism during the early ring stage resistance window, when lumefantrine was combined with artemether, an artemisinin derivative clinically partnered with lumefantrine. These findings suggest that lumefantrine should be clinically explored as a partner drug in artemisinin-based combination therapies to control emerging artemisinin resistance. (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu