Effect of drugs on the folic and folinic acid contents of erythrocytes infected with malaria parasites

Abstract

Treatment with sulfadiazine prevented most of the increase in folic and folinic acid which otherwise occurred in the red blood cells of ducks infected with Plasmodium lophurae. The same effect was observed when a sulfadiazine-resistant strain of P. lophurae was treated with sulfadiazine at doses having no effect on the infection: the increase in folic and folinic acids was markedly less than that in untreated infections with the same strain. When the sulfadiazine-resistant strain was treated with pyrimethamine, to which it was also resistant, the increase in folinic acid was inhibited, but not that in folic acid. Each drug exerted its characteristic inhibitory effect on the folinic acid-synthesizing mechanism, yet the parasites of the resistant strain continued to multiply. This synthetic mechanism may reside in the infected red cells rather than in the parasites. The resistance to sulfadiazine and pyrimethamine appears to depend on a decreased requirement for the products of the reactions inhibited by these drugs.