Changing Antimalarial Drug Resistance Patterns Identified by Surveillance at Three Sites in Uganda

J Infect Dis. 2017 Feb 15;215(4):631-635. doi: 10.1093/infdis/jiw614.

Abstract

We assessed Plasmodium falciparum drug resistance markers in parasites collected in 2012, 2013, and 2015 at 3 sites in Uganda. The prevalence and frequency of parasites with mutations in putative transporters previously associated with resistance to aminoquinolines, but increased sensitivity to lumefantrine (pfcrt 76T; pfmdr1 86Y and 1246Y), decreased markedly at all sites. Antifolate resistance mutations were common, with apparent emergence of mutations (pfdhfr 164L; pfdhps 581G) associated with high-level resistance. K13 mutations linked to artemisinin resistance were uncommon and did not increase over time. Changing malaria treatment practices have been accompanied by profound changes in markers of resistance.

Keywords: K13; Malaria; Plasmodium falciparum; amodiaquine; artemether; artemisinin; artesunate; chloroquine; dihydroartemisinin; drug resistance; lumefantrine; pfcrt; pfmdr1; piperaquine.

MeSH terms

  • Adolescent
  • Aminoquinolines / pharmacology
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology
  • Cross-Sectional Studies
  • DNA, Protozoan / isolation & purification
  • Drug Resistance / genetics*
  • Ethanolamines / pharmacology
  • Female
  • Fluorenes / pharmacology
  • Folic Acid Antagonists / pharmacology
  • Genes, Protozoan*
  • Humans
  • Lumefantrine
  • Malaria, Falciparum / drug therapy
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Mutation
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics
  • Polymorphism, Single Nucleotide
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Sequence Analysis, DNA
  • Uganda

Substances

  • Aminoquinolines
  • Antimalarials
  • Artemisinins
  • DNA, Protozoan
  • Ethanolamines
  • Fluorenes
  • Folic Acid Antagonists
  • Mdr1 protein, Plasmodium falciparum
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • PfCRT protein, Plasmodium falciparum
  • Protozoan Proteins
  • artemisinine
  • Lumefantrine