ArticleThe Journal of infectious diseases2017
Association of a Novel Mutation in the Plasmodium falciparum Chloroquine Resistance Transporter With Decreased Piperaquine Sensitivity.
Article in The Journal of infectious diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
90 citing papers in PubMed, 4 syntheses or guidelines pooled it, 145 citations in OpenAlex.
- Spatio-temporal trends of the prevalence of Plasmodium falciparum antimalarial drug resistance markers across sub-Saharan Africa from 2010 to 2024: a systematic review and meta-analysis.BMC infectious diseases · 2026Pooled it
- Plasmodium falciparum antimalarial resistance in Angola: a systematic review.Malaria journal · 2026Pooled it
- Prevalence of Plasmodium falciparum plasmepsin2/3 gene duplication in Africa and Asia: a systematic review and meta-analysis.Malaria journal · 2025Pooled it
- How has mass drug administration with dihydroartemisinin-piperaquine impacted molecular markers of drug resistance? A systematic review.Malaria journal · 2022Pooled it
- Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study.The Lancet. Infectious diseases · 2019Trial
- African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker.Malaria journal · 2019Trial
- Rhomboid Proteases in Plasmodium spp. : Biology, Functional Roles, and Therapeutic Potential.Acta parasitologica · 2026Review
- Advancing global malaria control: therapeutic strategies, drug discovery, and formulation innovations.Infection · 2026Review
- A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026Article
- 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
- Plasmodiumfalciparum protein kinase 6 and hemozoin formation are inhibited by a type II human kinase inhibitor exhibiting antimalarial activity.Cell chemical biology · 2025Article
- The plasmepsin-piperaquine paradox persists in Plasmodium falciparum.PLoS pathogens · 2025Article
- Plasmodium falciparum African PfCRT Mutant Isoforms Conducive to Piperaquine Resistance Are Infrequent and Impart a Major Fitness Cost.The Journal of infectious diseases · 2025Article
- Emerging Plasmodium falciparum K13 gene mutation to artemisinin-based combination therapies and partner drugs among malaria-infected population in sub-Saharan Africa.Parasites, hosts and diseases · 2025Review
- Deletion of theAntimicrobial agents and chemotherapy · 2025Article
- Low prevalence of copy number variation in pfmdr1 and pfpm2 in Plasmodium falciparum isolates from southern Angola.Malaria journal · 2025Article
- Controlled human malaria infection with NF54 and 7G8 strains elicit differential antibody responses to Plasmodium falciparum peptides.Frontiers in immunology · 2025Article
- Dihydroartemisinin-Piperaquine Combination in the Treatment of UncomplicatedJournal of clinical medicine · 2024Review
- Strong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum.Nature communications · 2024Article
- Assessing emergence risk of double-resistant and triple-resistant genotypes of Plasmodium falciparum.Nature communications · 2024Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 5 countries.
Funding
Abstract
Background: Amplified copy number in the plasmepsin II/III genes within Plasmodium falciparum has been associated with decreased sensitivity to piperaquine. To examine this association and test whether additional loci might also contribute, we performed a genome-wide association study of ex vivo P. falciparum susceptibility to piperaquine. Methods: Plasmodium falciparum DNA from 183 samples collected primarily from Cambodia was genotyped at 33716 genome-wide single nucleotide polymorphisms (SNPs). Linear mixed models and random forests were used to estimate associations between parasite genotypes and piperaquine susceptibility. Candidate polymorphisms were evaluated for their association with dihydroartemisinin-piperaquine treatment outcomes in an independent dataset. Results: Single nucleotide polymorphisms on multiple chromosomes were associated with piperaquine 90% inhibitory concentrations (IC90) in a genome-wide analysis. Fine-mapping of genomic regions implicated in genome-wide analyses identified multiple SNPs in linkage disequilibrium with each other that were significantly associated with piperaquine IC90, including a novel mutation within the gene encoding the P. falciparum chloroquine resistance transporter, PfCRT. This mutation (F145I) was associated with dihydroartemisinin-piperaquine treatment failure after adjusting for the presence of amplified plasmepsin II/III, which was also associated with decreased piperaquine sensitivity. Conclusions: Our data suggest that, in addition to plasmepsin II/III copy number, other loci, including pfcrt, may also be involved in 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.