Plasmodium falciparum: induction of resistance to mefloquine in cloned strains by continuous drug exposure in vitro.

A M Oduola, W K Milhous, N F Weatherly, J H Bowdre, R E Desjardins

Department of Parasitology and Laboratory Practice, School of Public Health, University of North Carolina, Chapel Hill 27514.

Experimental parasitology 1988 Dec

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A genetically homogeneous population of Plasmodium falciparum prepared by a single erythrocyte micromanipulation technique was used to produce lines of P. falciparum resistant to mefloquine hydrochloride in vitro. Parasites were maintained in a culture medium containing gradually increased concentrations of mefloquine hydrochloride (CMP-mef) starting with 2 ng/ml. One of the mefloquine-resistant culture lines (W2-mef) was obtained after 96 weeks of continuous culture in CMP-mef, the last 4 weeks in medium containing 40 ng/ml of mefloquine hydrochloride. The W2-mef was four to six times more resistant to mefloquine than was the parent clone W2. Means of multiple determinations of 50% inhibitory concentrations (IC-50) of mefloquine hydrochloride against W2-mef and clone W2 were 20.39 +/- 5.08 ng/ml and 4.50 +/- 1.94 ng/ml, respectively.

Citation

A M Oduola, W K Milhous, N F Weatherly, J H Bowdre, R E Desjardins. Plasmodium falciparum: induction of resistance to mefloquine in cloned strains by continuous drug exposure in vitro. Experimental parasitology. 1988 Dec;67(2):354-60