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January 4, 1971

Methotrexate Therapy for P vivax Malaria

Author Affiliations

Raleigh, NC

JAMA. 1971;215(1):117. doi:10.1001/jama.1971.03180140081018

To the Editor.—  The recent article by Sheehy and Dempsey on "Methotrexate Therapy for Plasmodium vivax Malaria" (214:109-114, 1970) contains statements concerning our present knowledge of the actions of folic acid antagonists in malaria which are deficient in content and misleading. The authors' claim that "only recently" has pyrimethamine been recognized as a folic acid antagonist is incorrect, in light of the many publications dating back to 1952 on the antifolate activity of this drug and of other similar compounds.1 Since that time the loci of action of pyrimethamine in plasmodia has been demonstrated to be inhibition of the dihydrofolate reductase of the parasite. This has been clearly shown in P berghei,2P lophurae,3 and P knowlesi.4 In P berghei, the drug binds to the enzyme from the parasite 2,000-fold more tightly than it binds to the enzyme from the host erythrocyte. Trimethoprim, cycloguanil, and