In Vitro and Clinical Correlates of Mefloquine Resistance of Plasmodium falciparum in Eastern Thailand

George E. ChildsUS Army Medical Component, Armed Forces Research Institute of Medical Sciences Bangkok, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, Thailand

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Ellen F. BoudreauUS Army Medical Component, Armed Forces Research Institute of Medical Sciences Bangkok, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, Thailand

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Theera WimonwattrateeUS Army Medical Component, Armed Forces Research Institute of Medical Sciences Bangkok, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, Thailand

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Lorrin PangUS Army Medical Component, Armed Forces Research Institute of Medical Sciences Bangkok, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, Thailand

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Wilbur K. MilhousUS Army Medical Component, Armed Forces Research Institute of Medical Sciences Bangkok, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, Thailand

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A series of isolates of Plasmodium falciparum from eastern Thailand was collected prior to and after treatment failure with mefloquine. Patterns of drug sensitivity to standard and new antimalarials were characterized by using an in vitro assay based on the inhibition of schizont maturation. In vitro levels of mefloquine sensitivity of isolates were correlated with clinical treatment failures. In vitro parasite resistance to mefloquine is defined as an inhibitory dose-50 value greater than 20 nM. For isolates collected prior to treatment, there was no significant difference in mefloquine sensitivity patterns between subsequent successes and failures, suggesting that mefloquine treatment failures could not be predicted based on in vitro sensitivity of pretreatment isolates. A series of paired isolates were collected both prior to treatment with mefloquine and after recrudescence. Recrudescent isolates showed significant decreases in sensitivity to mefloquine, WR 194965, enpiroline, and halofantrine; no significant changes in sensitivity to amodiaquine, qinghaosu, and pyrimethamine; and an increase in sensitivity to chloroquine.

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