Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum isolates from Sudanese malaria patients treated with artemether-lumefantrine

Antimicrob Agents Chemother. 2011 Nov;55(11):5408-11. doi: 10.1128/AAC.05102-11. Epub 2011 Sep 6.

Abstract

Molecular markers for surveillance of Plasmodium falciparum resistance to current antimalarials are sorely needed. A 28-day efficacy study of artemether-lumefantrine in eastern Sudan identified 5 treatment failures among 100 evaluable patients; 9 further individuals were parasite positive by PCR during follow-up. Polymorphisms in pfatpase6 and pfmdr1 were evaluated by DNA sequencing. One individual carried parasites with a novel pfmdr1 polymorphism (F1044L). pfmdr1 gene amplification in parasites prior to treatment occurred in three individuals who had recurrent infection during follow-up.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimalarials / therapeutic use*
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins / therapeutic use*
  • DNA Copy Number Variations / drug effects
  • DNA Copy Number Variations / genetics
  • Drug Combinations
  • Ethanolamines / therapeutic use*
  • Female
  • Fluorenes / therapeutic use*
  • Haplotypes
  • Humans
  • Longitudinal Studies
  • Malaria / drug therapy*
  • Malaria / parasitology
  • Male
  • Multidrug Resistance-Associated Proteins / genetics*
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / pathogenicity
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / drug effects
  • Polymorphism, Genetic / genetics
  • Young Adult

Substances

  • Antimalarials
  • Artemether, Lumefantrine Drug Combination
  • Artemisinins
  • Drug Combinations
  • Ethanolamines
  • Fluorenes
  • Mdr1 protein, Plasmodium falciparum
  • Multidrug Resistance-Associated Proteins