Methotrexate is highly potent against pyrimethamine-resistant Plasmodium vivax.
basic_science · Level V
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- Record sourced from PubMed, PMID 21288820.
- Also identified by DOI 10.1093/infdis/jiq024 and PMC identifier 3071051.
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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.
Medical subject headings
- Antimalarials
- Methotrexate
- Plasmodium vivax