Pigment Formation and Nuclear Division in Chloroquine-resistant Malaria Parasites (Plasmodium berghei, Vincke and Lips, 1948)

Abstract

THE emergence in widely separated areas of strains of Plasmodium falciparum resistant to standard prophylaxis or therapy with chloroquine and related 4-amino-quinoline derivatives^1–3 has led to a renewal of interest in the possible mechanisms of drug resistance in protozoa. Schueler and Cantrell⁴ and Cohen, Phifer and Yielding⁵ have recently proposed, on the basis of experiments with the rodent malaria parasite, P. berghei, that hæmatinic acid, which they state is an intermediary product formed during the metabolism of hæmoglobin to hæmatin, might be liberated in excess by certain parasite strains, that this porphyrin might form an insoluble complex with chloroquine and related drugs and that this could be a basis for the development by such parasites of tolerance towards certain chemotherapeutic agents. Hæmatin is known to be combined with a nitrogenous (peptide?) moiety to form the insoluble malaria pigment, hæmozoin⁶. Support for this hypothesis would be provided therefore by the demonstration that the quantity of the end product of hæmoglobin metabolism, hæmozoin, is decreased in those parasite strains which are able to liberate the soluble intermediary product, hæmatinic acid. In other words, there should be an inverse relationship between pigment formation and chloroquine resistance.