Cloning and characterization of mefloquine-resistant Plasmodium falciparum from Thailand.
Resistance to mefloquine in Plasmodium falciparum has begun to occur along the border of Thailand and Kampuchea. As a means of assessing the natural occurrence of mefloquine resistance, the admission and post-treatment parasite isolates from a mefloquine treatment failure were cloned and characterized. Clones from the admission isolate were susceptible to mefloquine in vitro (ID50 of 3.4 [2-5], G [95% CI] ng/ml) and showed a mixture of isozyme types for glucose phosphate isomerase (GPI types I and II). The post-treatment clones were resistant to mefloquine in vitro (ID50 of 17.3 [13-23] ng/ml) with only one isozyme (GPI type I) detected. These observations suggest that under mefloquine pressure a resistant parasite population was selected in the patient, indicating that the potential for mefloquine resistance already exists in the indigenous P. falciparum gene pool. In addition, the mefloquine-resistant clones showed decreased susceptibility in vitro to halofantrine suggesting possible cross-resistance to this new antimalarial drug currently under development.
D000328:Adult; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002999:Clone Cells; D004351:Drug Resistance; D005956:Glucose-6-Phosphate Isomerase / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D008288:Malaria / Q000188:drug therapy / Q000469:parasitology; D008297:Male; D015767:Mefloquine; D010616:Phenanthrenes / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000145:classification / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D013785:Thailand
D000962:Antimalarials; D007527:Isoenzymes; D010616:Phenanthrenes; D011804:Quinolines; D005956:Glucose-6-Phosphate Isomerase; C023768:halofantrine; D015767:Mefloquine