Resistance to primaquine in Plasmodium gallinaceum, and the problem of resistance to quinoline compounds in malaria parasites

Abstract

A tenfold enhancement of resistance to primaquine was obtained by maintaining a strain of Plasmodium gallinaceum in a state of acute infection by serial passage of infected blood through young chicks treated with gradually increasing doses of the drug.No loss in resistance to primaquine was observed when the resistant strain was transmitted through mosquitoes, though there was some loss in resistance to the maximum tolerated dose, but not to lower doses, when the strain was maintained in a state of acute infection through untreated chicks for 41 weeks.The primaquine-resistant strain was cross-resistant to lower effective doses of pamaquin, and slightly less sensitive to quinine than the parent strain but the loss in sensitivity to chloroquine was only marginal. Sensitivity to proguanil, dihydrotriazine and pyrimethamine was normal.Attempts were made to produce a chloroquine-resistant strain of P. gallinaceum using different doses of the drug but no change in sensitivity was observed though the experiments were continued for more than a year. An attempt to produce a chloroquine-resistant strain by treatment of a proguanil-resistant strain with chloroquine also failed.The problem of resistance to quinoline compounds in different species of Plasmodium is discussed.