ArticleNature communications2018
Plasmepsin II-III copy number accounts for bimodal piperaquine resistance among Cambodian Plasmodium falciparum.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Plasmodium falciparum antimalarial resistance in Angola: a systematic review.Malaria journal · 2026Pooled 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
- Decreased dihydroartemisinin-piperaquine protection against recurrent malaria associated with Plasmodium falciparum plasmepsin 3 copy number variation in Africa.Nature communications · 2025Trial
- Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial.The Lancet. Infectious diseases · 2021Trial
- Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial.Lancet (London, England) · 2020Trial
- African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker.Malaria journal · 2019Trial
- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- Cellular and molecular basis of PfCoronin function in artemisinin resistance in Plasmodium falciparum.Nature communications · 2026Article
- Border Region Surveillance of Malaria Drug Resistance, Northern Burundi, 2023-2024.Emerging infectious diseases · 2026Article
- Emergence of artemisinin-based combination therapy resistance markers inAntimicrobial agents and chemotherapy · 2026Article
- Changing genetic profiles ofAntimicrobial agents and chemotherapy · 2026Article
- Replication stress increases de novo CNVs across the malaria parasite genome.Nucleic acids research · 2026Article
- Genomic Plasticity and Molecular Mechanisms of Antimalarial Drug Resistance in Plasmodium falciparum: Implications for Treatment Failure and Genomic Surveillance.BioMed research international · 2026Review
- A review on molecular markers ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Review
- A scoping review of antimalarial drug resistance markers in Kenya (1987-2022): toward a National Surveillance Framework and Data Repository.Malaria journal · 2025Article
- Frequencies of molecular markers of drug resistance in the context of two different Seasonal Malaria Chemoprevention (SMC) treatment regimens in the Koulikoro health district, Mali.Antimicrobial agents and chemotherapy · 2025Article
- Replication stress increases de novo CNVs across the malaria parasite genome.bioRxiv : the preprint server for biology · 2025Article
- Epigenetically conferred ring-stage survival in Plasmodium falciparum against artemisinin treatment.Nature communications · 2025Article
- The plasmepsin-piperaquine paradox persists in Plasmodium falciparum.PLoS pathogens · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Multidrug resistant Plasmodium falciparum in Southeast Asia endangers regional malaria elimination and threatens to spread to other malaria endemic areas. Understanding mechanisms of piperaquine (PPQ) resistance is crucial for tracking its emergence and spread, and to develop effective strategies for overcoming it. Here we analyze a mechanism of PPQ resistance in Cambodian parasites. Isolates exhibit a bimodal dose-response curve when exposed to PPQ, with the area under the curve quantifying their survival in vitro. Increased copy number for plasmepsin II and plasmepsin III appears to explain enhanced survival when exposed to PPQ in most, but not all cases. A panel of isogenic subclones reinforces the importance of plasmepsin II-III copy number to enhanced PPQ survival. We conjecture that factors producing increased parasite survival under PPQ exposure in vitro may drive clinical PPQ failures in the field.
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