Kümpornsin, K. et al. (2021) Lumefantrine attenuates Plasmodium falciparum artemisinin resistance during the early ring stage. International Journal for Parasitology: Drugs and Drug Resistance, 17, pp. 186-190. (doi: 10.1016/j.ijpddr.2021.09.005) (PMID:34673330) (PMCID:PMC8528645)
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Abstract
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.
| Item Type: | Articles |
|---|---|
| Additional Information: | The work was supported by the Tres Cantos Open Lab Foundation, Wellcome (206194), the Bill and Melinda Gates Foundation (OPP1054480), Newton Advanced Fellowship under The Thailand Research Fund-Royal Society (DBG5980010) and the Faculty of Tropical Medicine, Mahidol University. DL was supported by Royal Golden Jubilee Ph.D. Program (Thailand Research Fund) and TRF-Newton Fund PhD Placement for Scholars (Thailand Research Fund and Newton Fund, United Kingdom). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Loesbanluechai, Ms Duangkamon |
| Authors: | Kümpornsin, K., Loesbanluechai, D., de Cozar, C., Kotanan, N., Chotivanich, K., White, N. J., Wilairat, P., Gomez-Lorenzo, M. G., Javier Gamo, F., Maria Sanz, L., Lee, M. C. S., and Chookajorn, T. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| Journal Name: | International Journal for Parasitology: Drugs and Drug Resistance |
| Publisher: | Elsevier |
| ISSN: | 2211-3207 |
| ISSN (Online): | 2211-3207 |
| Published Online: | 02 October 2021 |
| Copyright Holders: | Copyright © 2021 The Authors |
| First Published: | First published in International Journal for Parasitology: Drugs and Drug Resistance 17:186-190 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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