Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine

Publication date: Available online 1 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): 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 KümpornsinAbstractArtemisinin 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...
Source: International Journal for Parasitology: Drugs and Drug Resistance - Category: Parasitology Source Type: research