AMPLIFICATION OF PFMDR1 ASSOCIATED WITH MEFLOQUINE AND HALOFANTRINE RESISTANCE IN PLASMODIUM-FALCIPARUM FROM THAILAND

Drug resistance in Plasmodium falciparum is an expanding problem in most endemic areas. Recent studies have suggested the potential involvement of genes in the MDR gene family in resistance to quinoline-containing compounds in P. falciparum. In this study a molecular analysis of pfmdr1 in recent isolates from Thailand was done (1) to further examine the role of pfmdr1 in drug-resistant isolates and (2) to examine the reported association of pfmdr1 intragenic alleles and chloroquine resistance. Most of the isolates (10 of 11) were resistant to all compounds tested. Analysis of pfmdr1 revealed an apparent association between increased gene copy number and increased level of expression of pfmdr1 and decreased susceptibility to mefloquine and halofantrine. Sequence analysis of pfmdr1 in these isolates revealed no association of intragenic alleles with chloroquine resistance.