In vivo selection of Plasmodium falciparum Pfcrt and Pfmdr1 variants by artemether-lumefantrine and dihydroartemisinin-piperaquine in Burkina Faso

Vito Baraka; Halidou Tinto; Innocent Valea; Robert Fitzhenry; Christopher Delgado-Ratto; Martin K Mbonye; Chantal Van Overmeir; Anna Rosanas-Urgell; Jean-Pierre Van Geertruyden; Umberto D'Alessandro; Annette Erhart

doi:10.1128/AAC.03647-14

In vivo selection of Plasmodium falciparum Pfcrt and Pfmdr1 variants by artemether-lumefantrine and dihydroartemisinin-piperaquine in Burkina Faso

Antimicrob Agents Chemother. 2015 Jan;59(1):734-7. doi: 10.1128/AAC.03647-14. Epub 2014 Nov 17.

Affiliations

¹ National Institute for Medical Research, Tanga Medical Research Centre, Tanga, United Republic of Tanzania International Health Unit, Department of Epidemiology, University of Antwerp, Antwerp, Belgium vitobaraka@gmail.com.
² Centre Muraz, Bobo Dioulasso, Burkina Faso.
³ Malariology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
⁴ International Health Unit, Department of Epidemiology, University of Antwerp, Antwerp, Belgium.
⁵ International Health Unit, Department of Epidemiology, University of Antwerp, Antwerp, Belgium Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda.
⁶ Malariology Unit, Institute of Tropical Medicine, Antwerp, Belgium Medical Research Council, Banjul, the Gambia London School of Hygiene and Tropical Medicine, London, United Kingdom.

Abstract

Plasmodium falciparum Pfcrt-76 and Pfmdr1-86 gene polymorphisms were determined during a clinical trial in Burkina Faso comparing the efficacies of dihydroartemisinin-piperaquine (DHA-PPQ) and artemether-lumefantrine (AL). Significant selection of Pfcrt-K76 was observed after exposure to AL and DHA-PPQ, as well as selection of Pfmdr1-N86 after AL but not DHA-PPQ treatment, suggesting reverse selection on the Pfcrt gene by PPQ. These results support the rational use of DHA-PPQ in settings where chloroquine (CQ) resistance is high.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimanic Agents / administration & dosage
Antimanic Agents / therapeutic use*
Artemether, Lumefantrine Drug Combination
Artemisinins / administration & dosage
Artemisinins / therapeutic use*
Burkina Faso / epidemiology
Drug Combinations
Drug Resistance / genetics
Ethanolamines / therapeutic use*
Fluorenes / therapeutic use*
Genetic Variation / drug effects
Genetic Variation / genetics
Humans
Malaria, Falciparum / drug therapy*
Malaria, Falciparum / epidemiology
Malaria, Falciparum / genetics
Membrane Transport Proteins / genetics*
Multidrug Resistance-Associated Proteins / genetics*
Plasmodium falciparum / drug effects
Plasmodium falciparum / genetics*
Protozoan Proteins / genetics*
Quinolines / administration & dosage
Quinolines / therapeutic use*

Substances

Antimanic Agents
Artemether, Lumefantrine Drug Combination
Artemisinins
Drug Combinations
Ethanolamines
Fluorenes
Mdr1 protein, Plasmodium falciparum
Membrane Transport Proteins
Multidrug Resistance-Associated Proteins
PfCRT protein, Plasmodium falciparum
Protozoan Proteins
Quinolines
artenimol
piperaquine