ArticleGenome biology and evolution2017
Partner-Drug Resistance and Population Substructuring of Artemisinin-Resistant Plasmodium falciparum in Cambodia.
Article in Genome biology and evolution, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis 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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- How has mass drug administration with dihydroartemisinin-piperaquine impacted molecular markers of drug resistance? A systematic review.Malaria journal · 2022Pooled it
- African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker.Malaria journal · 2019Trial
- Signatures of pathogen-driven selection and Austronesian gene flow of Papua New Guinea HLA alleles.American journal of human genetics · 2026Article
- Towards an evolutionary baseline model ofbioRxiv : the preprint server for biology · 2025Article
- High prevalence and emerging positive association of kelch13 R622I and HRP2-based RDT negativity in Plasmodium falciparum in northern Ethiopia.PLoS pathogens · 2025Article
- Review
- Artemisinin resistantmedRxiv : the preprint server for health sciences · 2025Article
- Deletion of theAntimicrobial agents and chemotherapy · 2025Article
- Sensitive and modular amplicon sequencing of Plasmodium falciparum diversity and resistance for research and public health.Scientific reports · 2025Article
- Sensitive and modular amplicon sequencing ofbioRxiv : the preprint server for biology · 2025Article
- Article
- A novel 4-aminoquinoline chemotype with multistage antimalarial activity and lack of cross-resistance with PfCRT and PfMDR1 mutants.PLoS pathogens · 2024Article
- The emergence of artemisinin partial resistance in Africa: how do we respond?The Lancet. Infectious diseases · 2024Review
- AmBio · 2024Article
- Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.Medicina (Kaunas, Lithuania) · 2024Article
- Drug resistance and vaccine target surveillance of Plasmodium falciparum using nanopore sequencing in Ghana.Nature microbiology · 2023Article
- Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda.The New England journal of medicine · 2023Article
- Article
- Article
- Mutant PfCRT Can Mediate Piperaquine Resistance in African Plasmodium falciparum With Reduced Fitness and Increased Susceptibility to Other Antimalarials.The Journal of infectious diseases · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Plasmodium falciparum in western Cambodia has developed resistance to artemisinin and its partner drugs, causing frequent treatment failure. Understanding this evolution can inform the deployment of new therapies. We investigated the genetic architecture of 78 falciparum isolates using whole-genome sequencing, correlating results to in vivo and ex vivo drug resistance and exploring the relationship between population structure, demographic history, and partner drug resistance. Principle component analysis, network analysis and demographic inference identified a diverse central population with three clusters of clonally expanding parasite populations, each associated with specific K13 artemisinin resistance alleles and partner drug resistance profiles which were consistent with the sequential deployment of artemisinin combination therapies in the region. One cluster displayed ex vivo piperaquine resistance and mefloquine sensitivity with a high rate of in vivo failure of dihydroartemisinin-piperaquine. Another cluster displayed ex vivo mefloquine resistance and piperaquine sensitivity with high in vivo efficacy of dihydroartemisinin-piperaquine. The final cluster was clonal and displayed intermediate sensitivity to both drugs. Variations in recently described piperaquine resistance markers did not explain the difference in mean IC90 or clinical failures between the high and intermediate piperaquine resistance groups, suggesting additional loci may be involved in resistance. The results highlight an important role for partner drug resistance in shaping the P. falciparum genetic landscape in Southeast Asia and suggest that further work is needed to evaluate for other mutations that drive piperaquine resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.