Pyrimethamine resistance in Plasmodium vivax malaria.

P. vivax infection (Korean, St Elizabeth or Chesson strain) was induced in 17 neurosyphilitic patients. Pyrimethamine in single doses of either 25, 50, 100 or 200 mg was given to test the schizontocidal and sporontocidal effects.The first single-dose treatment of 25 mg or 100 mg was given between the 8th and 61st days of parasite patency and gave moderately rapid schizontocidal and very rapid sporontocidal effects. All observed cases relapsed.The second treatment, usually three weeks or longer after the first and with the same or higher doses, had either a diminished effect or none on the schizogonous and sporogonous cycles. Subsequent treatment, even at weekly intervals, had no effect.The resistant quality was undiminished in subsequent infections transmitted by mosquito bites, by the injection of preserved sporozoites, or by transfusion of infected blood. Preserving sporozoites or erythrocytic parasites at very low temperatures did not materially affect the resistant quality.In view of the evidence presented, it appears that resistance could also occur in the field when large single doses of pyrimethamine alone are given at less than monthly intervals to febrile persons having active P. vivax infections.