MODELING THE CHLOROQUINE CHEMOTHERAPY OF FALCIPARUM-MALARIA - THE VALUE OF SPACING A SPLIT-DOSE

We have attempted to provide a rational basis for improving the protoc ols for chemotherapy of malaria. We model the regression of parasitaem ia by Plasmodium falciparum, its subsequent elimination from the body, or recrudescence, for populations of cells treated with chloroquine. Our model assumes that the drug forms a complex with some receptor in the parasite and that parasites possessing this complex die at a defin ed rate. We take into account that chloroquine is eliminated exponenti ally from the body. We show how the parameters of the model can be der ived from observations in the field. The model correctly predicts the effects of drug dose, degree of initial parasitaemia, rate of parasite multiplication and degree of drug resistance to chloroquine chemother apy. The level of parasitaemia will reduce to a minimum at sufficientl y high concentrations of chloroquine, but only if the parasitaemia is reduced to below that of 1 parasite per infected person will a cure of malaria be obtained. Otherwise, recrudescence mill, sooner or later, occur. We show that, even for drug-resistant malaria, if 2 doses of ch loroquine are given to a patient with an interval of some 10 days betw een them, parasites can be eliminated from the body without toxic leve ls of chloroquine being reached.