J Infect Dis. 2011 Jan 15;203(2):207-10. Epub 2010 Dec 9.

Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax.

Imwong M, Russell B, Suwanarusk R, Nzila A, Leimanis ML, Sriprawat K, Kaewpongsri S, Phyo AP, Snounou G, Nosten F, Renia L.

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Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok.

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 [IC₅₀], 13,345 nM), these parasites were all highly susceptible to MTX (median IC₅₀, 2.6 nM). Given its potency against Pyr-resistant P. vivax, the antimalarial potential of MTX deserves further investigation.

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J Infect Dis. 2011 Jan 15;203(2):144-5.

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PMCID:: PMC3071051

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