The development of pyrimethamine resistance by Plasmodium falciparum.

Sixteen patent P. falciparum infections (McLendon and Panama strains) in non-immunes were treated with single doses of pyrimethamine. The schizontocidal and sporontocidal response to the initial dose was rapid.Seven blood-induced infections, of which three were treated with 100 mg and four with 50 mg, did not relapse. Of seven cases observed after 25-mg treatment, five relapsed.Delayed treatment of the relapsing infections (Panama strain) with single doses of 25 mg or 50 mg, and subsequently 100 mg, had virtually no schizontocidal or sporontocidal effect. In one case the resistant infection was transmitted by mosquitos to another patient; the subsequent infection was also highly resistant to the drug.It is concluded that under the experimental conditions of this study resistance to pyrimethamine by P. falciparum may occur rapidly after a single dose of 25 mg, being manifested during relapses on the second challenge with the drug. Increasing the drug dosage does not overcome the resistance. The resistant character is readily transmitted by mosquitos.