Resistance of East African varieties of Plasmodium falciparum to pyrimethamine

Abstract

The appearance of pyrimethamine (daraprim) resistant strains of Plasmodium falciparum all the way from Malaya to East Africa is of considerable medical concern. Experimental tests in East Africa confirmed the fact that use of daraprim therapy will cause appearance of non-susceptible strains of P. falciparum, and therefore the value of the drug in prophylaxis is lessened. Cessation of treatment, however, showed that such non-susceptible strains soon were lost sight of and had not crowded out susceptible strains, which soon restablished themselves in a dominant position. The action of daraprim is believed to be based on its suppression of the normal mitotic activity of the parasite during schizogony and oocyst maturation through the blocking of the action of folinic and p-aminobenzoic acids necessary for nutritional growth. The resistant strains seemed to be those parasites capable of using the nutrients in spite of the drug block, but such strains could not compete with parasites enjoying normal nutrition and soon become lost from view.