An in vitro assay system for the identification of potential antimalarial drugs.
Current models for antimalarial drug screening generally measure the survival of drug-treated rodents infected with Plasmodium berghei. Modifications of existing continuous culture methods for P. falciparum allow the rapid, accurate and economical determination of drug effects directly against the human pathogen. Parasite cultures can be maintained in RPMI 1640 medium supplemented with human or rabbit serum or with hypoxanthine-supplemented bovine serum. The antiparasite effects of four drugs, chloroquine, chloramphenicol, clindamycin, and halofuginone, are identical in these sera; drugs can be screened routinely against P. falciparum grown in bovine serum supplemented with hypoxanthine. Drug effects may be rapidly and accurately determined by monitoring the incorporation of 3H-hypoxanthine into parasite nucleic acids. Results obtained with this technique are highly correlated with those derived from visual counting of parasites in thin blood films. Compounds with antimalarial activity in culture may be further screened by measuring the effects of serum obtained from drug-treated rabbits on parasites in culture. The advantages of this system over models currently used for antimalarial screening are discussed.
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002417:Cattle; D002701:Chloramphenicol / Q000494:pharmacology; D002738:Chloroquine / Q000494:pharmacology; D002981:Clindamycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D010880:Piperidines; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011799:Quinazolines / Q000494:pharmacology; D052999:Quinazolinones; D011817:Rabbits
D000962:Antimalarials; D007042:Hypoxanthines; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; D019271:Hypoxanthine; D002981:Clindamycin; D002701:Chloramphenicol; D002738:Chloroquine; C010176:halofuginone