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Title: Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax
Authors: Mallika Imwong
Bruce Russell
Rossarin Suwanarusk
Alexis Nzila
Mara L. Leimanis
Kanlaya Sriprawat
Supaporn Kaewpongsri
Aung Pyae Phyo
Georges Snounou
Francois Nosten
Laurent Renia
Mahidol University
Shoklo Malaria Research Unit
Agency for Science, Technology and Research, Singapore
Kenya Medical Research Institute
Hopital Pitie Salpetriere
Universite Pierre et Marie Curie
Centre for Clinical Vaccinology and Tropical Medicine
Keywords: Medicine
Issue Date: 15-Jan-2011
Citation: Journal of Infectious Diseases. Vol.203, No.2 (2011), 207-210
Abstract: Resistance of vivax malaria to treatment with antifolates, such as pyrimethamine (Pyr), is spreading as mutations in the dihydrofolatereductase (dhfr) genes are selected and disseminated. We tested the antitumor drug methotrexate (MTX), a potent competitive inhibitor of dhfr, against 11 Plasmodium vivax isolates ex vivo, 10 of which had multiple dhfr mutations associated with Pyr resistance. Despite high-grade resistance to Pyr (median 50% inhibitory concentration [IC 50 ], 13,345 nM), these parasites were all highly susceptible to MTX (median IC 50 , 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
ISSN: 00221899
Appears in Collections:Scopus 2011-2015

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