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|Title:||Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax|
Mara L. Leimanis
Aung Pyae Phyo
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
|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.|
|Appears in Collections:||Scopus 2011-2015|
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