Qinghaosu resistance in rodent malaria.

Resistance to qinghaosu (artemisinin) developed rapidly in a chloroquine-resistant line of Plasmodium yoelii (NS) passaged in mice, but was not produced in chloroquine-sensitive P. berghei. Development of resistance took place in an apparently stepwise fashion. After removal of drug selection pressure some resistance was lost which was regained rapidly within three passages when drug pressure was reapplied. The resistant QS line was cross-resistant to two reduced derivatives of artemisinin but not to propoxycarbonyl dihydroartemisinin or artesunate. No significant resistance was shown against primaquine, pyrimethamine, cycloguanil or pyrimethamine-sulphadoxine, but resistance to chloroquine was enhanced and marked resistance to quinine, mefloquine and amodiaquine was noted. It is suggested that the unusual cross-resistance pattern of the strain relates to changes in membrane characteristics.