Polymorphism of the Plasmodium falciparum multidrug resistance and chloroquine resistance transporter genes and in vitro susceptibility to aminoquinolines in isolates from the Peruvian Amazon

Am J Trop Med Hyg. 2004 May;70(5):461-6.

Abstract

In vitro drug sensitivity to chloroquine (CQ), mefloquine (MQ) and quinine was investigated in 60 culture-adapted Plasmodium falciparum isolates from malaria patients in Padrecocha, a village in the Amazonian Department of Loreto, Peru. All isolates showed resistance to CQ, decreased susceptibility to quinine, and sensitivity to MQ. These isolates were examined for mutations in the P. falciparum multidrug resistance 1 (pfmdr1) and chloroquine resistance transporter (pfcrt) genes previously linked to CQ resistance. The mutations N86Y and D1246Y, two of the five mutations commonly observed in the pfmdr1 gene of CQ-resistant clones, were not found. The pfcrt mutation K76T, associated with CQ resistance, was identified in all the isolates tested. Sequence analysis of codons 72-76 in the pfcrt gene showed the haplotypes SVMNT and CVMNT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Chloroquine / pharmacology*
  • Drug Resistance, Multiple
  • Genes, MDR*
  • Genotype
  • Mefloquine / pharmacology
  • Membrane Proteins* / genetics*
  • Membrane Transport Proteins
  • Mutation
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Polymorphism, Genetic*
  • Protozoan Proteins
  • Quinine / pharmacology

Substances

  • Antimalarials
  • Membrane Proteins
  • Membrane Transport Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine
  • Quinine
  • Mefloquine