West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia

Am J Trop Med Hyg. 2016 Nov 2;95(5):1054-1060. doi: 10.4269/ajtmh.16-0053. Epub 2016 Aug 22.

Abstract

In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites.

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Antimalarials / therapeutic use*
  • Artemether
  • Artemisinins / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Resistance / genetics*
  • Ethanolamines / therapeutic use*
  • Fluorenes / therapeutic use*
  • Follow-Up Studies
  • Gambia
  • Genetic Loci
  • Humans
  • Lumefantrine
  • Malaria, Falciparum / drug therapy*
  • Mali
  • 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
  • Senegal
  • Young Adult

Substances

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