Rapid selection of Plasmodium falciparum chloroquine resistance transporter gene and multidrug resistance gene-1 haplotypes associated with past chloroquine and present artemether-lumefantrine use in Inhambane District, southern Mozambique

Am J Trop Med Hyg. 2013 Mar;88(3):536-41. doi: 10.4269/ajtmh.12-0525. Epub 2013 Feb 4.

Abstract

Chloroquine (CQ) use in Mozambique was stopped in 2002 and artemether-lumefantrine (AL) was implemented in 2008. In light of no use of CQ and extensive use of AL, we determined the frequency of molecular markers of Plasmodium falciparum drug resistance/tolerance to CQ and AL in persons living in Linga-Linga, an isolated peninsula and in Furvela village, which is located 8 km inland. The P. falciparum chloroquine resistance transporter gene CVMNK wild type increased in frequency from 43.9% in 2009 to 66.4% in 2010 (P ≤ 0.001), and combined P. falciparum multidrug resistance gene 1 N86-184F-D1246 haplotype increased significantly between years (P = 0.039). The combination of P. falciparum chloroquine resistance transporter gene CVMNK and P. falciparum multidrug resistance gene NFD increased from 24.3% (2009) to 45.3% in (2010, P = 0.017). The rapid changes observed may largely be caused by decreased use of CQ and large-scale use of AL. In the absence of a clear AL-resistance marker and the (almost) continent-wide use of AL in sub-Saharan Africa, and when considering CQ reintroduction, continued monitoring of these markers is needed.

MeSH terms

  • Antimalarials / pharmacology
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / administration & dosage
  • Artemisinins / therapeutic use*
  • Chloroquine / pharmacology
  • Chloroquine / therapeutic use*
  • DNA, Protozoan / genetics
  • Drug Combinations
  • Drug Resistance / genetics*
  • Ethanolamines / administration & dosage
  • Ethanolamines / therapeutic use*
  • Fluorenes / administration & dosage
  • Fluorenes / therapeutic use*
  • Haplotypes
  • Humans
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / parasitology
  • Membrane Transport Proteins
  • Mozambique / epidemiology
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / metabolism
  • Polymorphism, Single Nucleotide
  • Protozoan Proteins
  • Selection, Genetic*
  • Time Factors

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • DNA, Protozoan
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Mdr1 protein, Plasmodium falciparum
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • Chloroquine