ArticleInternational journal for parasitology. Drugs and drug resistance2019
Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine.
Article in International journal for parasitology. Drugs and drug resistance, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 3 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Drug resistance of Plasmodium falciparum and Plasmodium vivax isolates in Indonesia.Malaria journal · 2022Pooled it
- How has mass drug administration with dihydroartemisinin-piperaquine impacted molecular markers of drug resistance? A systematic review.Malaria journal · 2022Pooled it
- Artemisinin-based combination therapy (ACT) and drug resistance molecular markers: A systematic review of clinical studies from two malaria endemic regions - India and sub-Saharan Africa.International journal for parasitology. Drugs and drug resistance · 2021Pooled it
- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- A review on molecular markers ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- The plasmepsin-piperaquine paradox persists in Plasmodium falciparum.PLoS pathogens · 2025Article
- Article
- Dihydroartemisinin-Piperaquine Combination in the Treatment of UncomplicatedJournal of clinical medicine · 2024Review
- AmBio · 2024Article
- Combating antimicrobial resistance in malaria, HIV and tuberculosis.Nature reviews. Drug discovery · 2024Review
- Mapping the genomic landscape of multidrug resistance inScience advances · 2023Article
- Article
- Article
- A single point mutation in the Plasmodium falciparum 3'-5' exonuclease does not alter piperaquine susceptibility.Malaria journal · 2022Article
- Evaluations of candidate markers of dihydroartemisinin-piperaquine resistance in Plasmodium falciparum isolates from the China-Myanmar, Thailand-Myanmar, and Thailand-Cambodia borders.Parasites & vectors · 2022Article
- Evaluation of the Effect of Gene Duplication by Genome Editing on Drug Resistance inFrontiers in cellular and infection microbiology · 2022Article
- Longitudinal ex vivo and molecular trends of chloroquine and piperaquine activity against Plasmodium falciparum and P. vivax before and after introduction of artemisinin-based combination therapy in Papua, Indonesia.International journal for parasitology. Drugs and drug resistance · 2021Article
- Evolution of Multidrug Resistance in Plasmodium falciparum: a Longitudinal Study of Genetic Resistance Markers in the Greater Mekong Subregion.Antimicrobial agents and chemotherapy · 2021Article
- Plasmodium falciparum resistance to ACTs: Emergence, mechanisms, and outlook.International journal for parasitology. Drugs and drug resistance · 2021Article
- Plasmodium falciparum phenotypic and genotypic resistance profile during the emergence of Piperaquine resistance in Northeastern Thailand.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 4 countries.
Funding
Abstract
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.
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Registered trials
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