Selection of drug-resistant P.falciparum parasites as a consequence of the use of long half-life antimalarial drugs

ABSTRACT

The pharmacokinetic characteristics of individual drugs may influence the epidemiology of drug resistance in malaria. Pyrimethamine-sulfadoxine (PSD); an effective malaria treatment in Kenya; has long elimination half-life. Although the initial; disease-producing parasite population may be eradicated by treatment; in theory; parasites which re-infect the host may be subjected to selection by residual drug. From in vitro chemosensitivity data; and a knowledge of the pharmacokinetic parameters for the two drugs; a Regsistance Selection Period (RSP) was defined for PSD. In a field trial at Kilifi; reinfection of study subjects during the RSP by pyrimethamine-resistant parasites was more frequent tahn by sensitive parasites. At times after treatment beyond RSP; the frequency of resistant parasites was not significantly different to the frequency before treatment. These results are discussed in terms of the increasing use of PSD to treat falciparum malaria in Africa; and the feneral relationship between elimination half-life and resistance selection