Plasmodium falciparum antimalarial drug susceptibility on the north-western border of Thailand during five years of extensive use of artesunate-mefloquine

Following a marked decline in the efficacy in vivo of mefloquine between 19 90 and 1994, a combination of artesunate (4 mg/kg/d for 3 d) and mefloquine (25 mg/kg) has been used as first line treatment of uncomplicated falcipar um malaria in camps for displaced persons located along the north-western b order of Thailand. Antimalarial drug susceptibility of fresh isolates of Pl asmodium falciparum from this population was evaluated using a radioisotope microdilution assay between 1995 and 1999. In total, 268 isolates were col lected, of which 189 were from primary infections and 79 from recrudescent infections. The geometric mean 50% inhibitory concentration (IC50) values f rom primary infections were: dihydroartemisinin 1(.)2 ng/mL, artesunate 1(. )6 ng/mL, artemether 4(.)8 ng/mL, atovaquone 0(.)4 ng/mL, lumefantrine 32 n g/ml, chloroquine 149 ng/mL, quinine 354 ng/mL, mefloquine 27 ng/mL and hal ofantrine 4(.)1 ng/mL. A significant positive correlation was found between the susceptibility in vitro to artesunate and quinine (r = 0.43, P < 0(.)0 01), mefloquine (r = 0(.)46, P < 0(.)001), and halofantrine (r = 0(.)51, P < 0(.)001). These levels of resistance in vitro are among the highest repor ted and confirm continuing high level multidrug resistance in this area. De spite intensive use of thr combination between 1995 and 1999 there has been a significant improvement in mefloquine sensitivity (P < 0(.)001) and arte sunate sensitivity (P < 0(.)001). This supports observations in vivo that t he combination of artesunate and mefloquine has reversed the previous decli ne in mefloquine sensitivity.