Effect of Drug Pressure on Promoting the Emergence of Antimalarial-Resistant Parasites among Pregnant Women in Ghana

Antimicrob Agents Chemother. 2020 May 21;64(6):e02029-19. doi: 10.1128/AAC.02029-19. Print 2020 May 21.

Abstract

The continuous spread of antimalarial drug resistance is a threat to current chemotherapy efficacy. Therefore, characterizing the genetic diversity of drug resistance markers is needed to follow treatment effectiveness and further update control strategies. Here, we genotyped Plasmodium falciparum resistance gene markers associated with sulfadoxine-pyrimethamine (SP) and artemisinin-based combination therapy (ACT) in isolates from pregnant women in Ghana. The prevalence of the septuple IRN I- A/FG K GS/Tpfdhfr/pfdhps haplotypes, including the pfdhps A581G and A613S/T mutations, was high at delivery among post-SP treatment isolates (18.2%) compared to those of first antenatal care (before initiation of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine [IPTp-SP]; 6.1%; P = 0.03). Regarding the pfk13 marker gene, two nonsynonymous mutations (N458D and A481C) were detected at positions previously related to artemisinin resistance in isolates from Southeast Asia. These mutations were predicted in silico to alter the stability of the pfk13 propeller-encoding domain. Overall, these findings highlight the need for intensified monitoring and surveillance of additional mutations associated with increased SP resistance as well as emergence of resistance against artemisinin derivatives.

Keywords: Plasmodium falciparum; artemisinin; drug resistance; pfdhfr; pfdhps; pfk13; sulfadoxine-pyrimethamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials* / pharmacology
  • Antimalarials* / therapeutic use
  • Drug Combinations
  • Drug Resistance / genetics
  • Female
  • Ghana
  • Humans
  • Malaria, Falciparum* / drug therapy
  • Parasites*
  • Pharmaceutical Preparations*
  • Plasmodium falciparum / genetics
  • Pregnancy
  • Pregnant Women
  • Protozoan Proteins / therapeutic use
  • Pyrimethamine / pharmacology
  • Pyrimethamine / therapeutic use
  • Sulfadoxine / pharmacology
  • Sulfadoxine / therapeutic use
  • Tetrahydrofolate Dehydrogenase / genetics

Substances

  • Antimalarials
  • Drug Combinations
  • Pharmaceutical Preparations
  • Protozoan Proteins
  • Sulfadoxine
  • Tetrahydrofolate Dehydrogenase
  • Pyrimethamine