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

Bernard Tornyigah; Romain Coppée; Pascal Houze; Kwadwo A Kusi; Bright Adu; Isabella Quakyi; Nathaniel Coleman; Atikatou Mama; Philippe Deloron; Abraham K Anang; Jérôme Clain; Rachida Tahar; Michael F Ofori; Nicaise Tuikue Ndam

doi:10.1128/AAC.02029-19

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.

Authors

Bernard Tornyigah^{1

2}, Romain Coppée³, Pascal Houze^{4

5}, Kwadwo A Kusi², Bright Adu², Isabella Quakyi⁶, Nathaniel Coleman⁶, Atikatou Mama³, Philippe Deloron³, Abraham K Anang⁷, Jérôme Clain³, Rachida Tahar³, Michael F Ofori², Nicaise Tuikue Ndam^{1

2}

Affiliations

¹ Université de Paris, Paris, France [email protected] [email protected].
² Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.
³ Université de Paris, Paris, France.
⁴ Service de biochimie générale, Hôpital universitaire Necker-Enfants Malades, Paris, France.
⁵ Unité de Technologies Biologiques et Chimiques pour la Santé (UTCBS), CNRS UMR8258, INSERM U1022, Faculté de Pharmacie, Université de Paris, Paris, France.
⁶ Department of Biological Environmental and Occupational Health Sciences, School of Public Health, College of Health Sciences , University of Ghana, Legon, Ghana.
⁷ Department of Parasitology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Legon, Ghana.

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