Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax

• Main 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
• Other Authors: Mahidol University
• Format: Article
• Published: 2018
• Subjects: Medicine
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/12700

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.