Chemotherapy of Rodent Malaria. Part 1.

Blood schizontocidal action of 2 WRAIR compounds and 3 compounds from other sources is summarized in this report. WR 254594 has slight antimalarial activity and BL 09686 is moderately active. Invermectin shows no evidence of antimalarial activity, whilst doxycycline is shown to be 10 times more active than tetracycline. The quinolone ester, ICI 56780, is highly active when administered subcutaneously but far less so when given orally. Causal prophylactic activity data are included for 4 WRAIR compounds, ICI 56780 and 5 primaquine metabolites. The most active WRAIR compound is WR 254419. The ICI compound and 4 of the 5 primaquine metabolites also showed tissue schizontocidal activity. 3 WRAIR compounds and ICI 56780 were tested for gametocytocidal activity, none were as active as primaquine. Halofantrine and 5 other WRAIR compounds were tested for activity against the sporogonic stages of P.y.nigeriensis, the most active of these was BL 09686. 7 primaquine derivatives tested in this system showed little or no activity. A method for in vitro testing of drugs against the exoerythrocytic stages of P.yoelii is described and test data showing the direct action of primaquine and ICI 56780 on tissue schizonts are given. Details of the development of 2 amodiaquine-resistant strains of rodent malaria and cross-resistance studies against a range of drug-resistant strains to 16 different known antimalarials are included. Keywords Drug resistance. KT