Analysis of mefloquine resistance and amplification of pfmdr1 in multidrug-resistant Plasmodium falciparum isolates from Thailand

Resistance to quinoline-containing compound has been associated with the Pl asmodium falciparum multidrug resistance 1 (pfmdr1) gene. We analyzed wild P. falciparum isolates with high levels of chloroquine and mefloquine resis tance for their macrorestriction maps of chromosome 5 and sequence of pfmdr 1. Two types of chromosome 5 amplification were found, Eleven of 62 resista nt isolates displayed Bgl I fragments larger than 100 kb. Twenty-nine isola tes possessed multiple copies of the fragments. We failed to detect any amp lification of this region on chromosome 5 in 22 mefloquine-resistant isolat es, suggesting that other mechanisms can mediate the mefloquine-resistant p henotype. There was no direct association between pfmdr1 mutations and chlo roquine sensitivity. Resistant lines could have Asn-86 and Tyr-184 or Phe-1 84, the predicted sequence of those chloroquine-sensitive isolates. No muta tion at Asn-1042 and Asp-1246 was detected among these chloroquine-resistan t isolates. Therefore, a few base substitutions in the pfmdr1 gene may not be sufficient to account for all chloroquine-resistant phenotypes.