Simple jQuery Dropdowns
Please use this identifier to cite or link to this item:
Title: Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine
Authors: Duangkamon Loesbanluechai
Namfon Kotanan
Cristina de Cozar
Theerarat Kochakarn
Megan R. Ansbro
Kesinee Chotivanich
Nicholas J. White
Prapon Wilairat
Marcus C.S. Lee
Francisco Javier Gamo
Laura Maria Sanz
Thanat Chookajorn
Krittikorn Kümpornsin
GlaxoSmithKline plc, Spain
Churchill Hospital
National Institute of Allergy and Infectious Diseases
Mahidol University
Wellcome Sanger Institute
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Apr-2019
Citation: International Journal for Parasitology: Drugs and Drug Resistance. Vol.9, (2019), 16-22
Abstract: © 2018 The Authors Artemisinin derivatives and their partner drugs in artemisinin combination therapies (ACTs) have played a pivotal role in global malaria mortality reduction during the last two decades. The loss of artemisinin efficacy due to evolving drug-resistant parasites could become a serious global health threat. Dihydroartemisinin-piperaquine is a well tolerated and generally highly effective ACT. The implementation of a partner drug in ACTs is critical in the control of emerging artemisinin resistance. Even though artemisinin is highly effective in parasite clearance, it is labile in the human body. A partner drug is necessary for killing the remaining parasites when the pulses of artemisinin have ceased. A population of Plasmodium falciparum parasites in Cambodia and adjacent countries has become resistant to piperaquine. Increased copy number of the genes encoding the haemoglobinases Plasmepsin II and Plasmepsin III has been linked with piperaquine resistance by genome-wide association studies and in clinical trials, leading to the use of increased plasmepsin II/plasmepsin III copy number as a molecular marker for piperaquine resistance. Here we demonstrate that overexpression of plasmepsin II and plasmepsin III in the 3D7 genetic background failed to change the susceptibility of P. falciparum to artemisinin, chloroquine and piperaquine by both a standard dose-response analysis and a piperaquine survival assay. Whilst plasmepsin copy number polymorphism is currently implemented as a molecular surveillance resistance marker, further studies to discover the molecular basis of piperaquine resistance and potential epistatic interactions are needed.
ISSN: 22113207
Appears in Collections:Scopus 2019

Files in This Item:
There are no files associated with this item.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.