HIGH-LEVEL CHLOROQUINE RESISTANCE OF PLASMODIUM-BERGHEI IS ASSOCIATEDWITH MULTIPLE-DRUG RESISTANCE AND LOSS OF REVERSAL BY CALCIUM-ANTAGONISTS

The chloroquine resistance of Plasmodium falciparum is reversed in vit ro by numerous compounds, including calcium antagonists, which could e nhance the accumulation of the drug in the parasite food vacuole. Howe ver, this mechanism of resistance could be insufficient when the resis tance level increases. Using in-vitro drug trials on strains of Plasmo dium berghei displaying various chloroquine-resistance levels, we conf irmed previous results obtained in vivo in that chloroquine-resistant strains of P. berghei are cross-resistant to related drugs (amodiaquin e, quinine and mefloquine), the resistance levels to these drugs being related to their analogy to chloroquine. Furthermore, we showed that high-level resistant lines were associated with a loss of drug potenti ation by verapamil and nicardipine in vivo, but that the reversal rate s obtained in vitro are of low significance. We conclude that the para site is able to escape the activity of these reversing agents. (C) 199 8 Australian Society for Parasitology. Published by Elsevier Science L td.