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Title: Analysis of mefloquine resistance and amplification of pfmdr1 in multidrug-resistant Plasmodium falciparum isolates from Thailand
Authors: Sansanee C. Chaiyaroj
Akanit Buranakiti
Pornpimon Angkasekwinai
Sornchai Looareesuwan
Alan F. Cowman
Mahidol University
Walter and Eliza Hall Institute of Medical Research
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Jan-1999
Citation: American Journal of Tropical Medicine and Hygiene. Vol.61, No.5 (1999), 780-783
Abstract: Resistance to quinoline-containing compound has been associated with the Plasmodium falciparum multidrug resistance 1 (pfmdr1) gene. We analyzed wild P. falciparum isolates with high levels of chloroquine and mefloquine resistance for their macrorestriction maps of chromosome 5 and sequence of pfmdr1. Two types of chromosome 5 amplification were found. Eleven of 62 resistant isolates displayed Bgl I fragments larger than 100 kb. Twenty-nine isolates possessed multiple copies of the fragments. We failed to detect any amplification of this region on chromosome 5 in 22 mefloquine-resistant isolates, suggesting that other mechanisms can mediate the mefloquine- resistant phenotype. There was no direct association between pfmdr1 mutations and chloroquine sensitivity. Resistant lines could have Asn-86 and Tyr-184 or Phe-184, the predicted sequence of those chloroquine-sensitive isolates. No mutation at Asn-1042 and Asp-1246 was detected among these chloroquine- resistant isolates. Therefore, a few base substitutions in the pfmdr1 gene may not be sufficient to account for all chloroquine-resistant phenotypes.
ISSN: 00029637
Appears in Collections:Scopus 1991-2000

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