Trial reportNature genetics2015
Genetic architecture of artemisinin-resistant Plasmodium falciparum.
Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph
Trial report in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 392 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
392citing papers in PubMed, 2 pooled it
78.4field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
392 citing papers in PubMed, 2 syntheses or guidelines pooled it, 639 citations in OpenAlex.
- Spatio-temporal trends of artemisinin-based combination therapy efficacy from 2010 to 2024 in sub-Saharan Africa: a systematic review and meta-analysis.BMC infectious diseases · 2025Pooled it
- Identification of Co-Existing Mutations and Gene Expression Trends Associated With K13-Mediated Artemisinin Resistance inFrontiers in genetics · 2022Pooled it
- Trial
- 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
- 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
- Nanoparticle based drug delivery systems improve antimalarial efficacy and vaccine performance in African research and clinical settings.Discover nano · 2026Review
- Genomic surveillance reveals co-occurrence of Plasmodium falciparum drug resistance variants across diverse transmission settings in Ethiopia.Nature microbiology · 2026Article
- PfATG18 links V-ATPase assembly to endocytic membrane dynamics in malaria parasites.PLoS pathogens · 2026Article
- Genome-wide characterization of Plasmodium vivax infections in local travelers and non-travelers from the Peruvian Amazon.Research square · 2026Article
- Drug resistance gene polymorphisms of Plasmodium falciparum clinical isolates from Kinshasa, Democratic Republic of the Congo.Tropical medicine and health · 2026Article
- Spatial and temporal description of antimalarial drug resistance markers in Ghana using targeted amplicon deep sequencing.Antimicrobial agents and chemotherapy · 2026Article
- Hemoglobin Digestion Genes Are Conserved in Lizard-InfectiveEcology and evolution · 2026Article
- Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.Nature communications · 2026Article
- Continental-scale genomic surveillance of Plasmodium falciparum malaria across sub-Saharan Africa with rapid nanopore sequencing.Nature communications · 2026Article
- National genomic profiling of Plasmodium falciparum antimalarial resistance in Zambian children participating in the 2018 malaria indicator survey.Scientific reports · 2026Article
- Functional assessment of prevalentmBio · 2026Article
- Double Mutations inbioRxiv : the preprint server for biology · 2026Article
- Molecular markers of antimalarial drug resistance in pfk13, pfmdr1, pfdhfr, and pfdhps genes of Plasmodium falciparum in a rural municipality in Cubal, Benguela Province, Angola (2022-2023).Malaria journal · 2026Article
- Genomic Plasticity and Molecular Mechanisms of Antimalarial Drug Resistance in Plasmodium falciparum: Implications for Treatment Failure and Genomic Surveillance.BioMed research international · 2026Review
- Molecular mechanisms underlying drug resistance in protozoan parasites: emerging mechanisms and therapeutic perspectives.Frontiers in parasitology · 2026Review
332 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
50 authors at 16 institutions in 12 countries.
Olivo Miotto1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [3] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.ORCID 0000000180606771
Roberto Amato1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.ORCID 0000000186339221
Elizabeth A Ashley1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Bronwyn MacInnis1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK.
Jacob Almagro-Garcia1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Chanaki AmaratungaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
Pharath Lim1] Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA. [2] National Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Daniel MeadWellcome Trust Sanger Institute, Hinxton, UK.
Samuel O OyolaWellcome Trust Sanger Institute, Hinxton, UK.
Mehul Dhorda1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [2] Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA. [3] WorldWide Antimalarial Resistance Network (WWARN), Asia Regional Centre, Mahidol University, Bangkok, Thailand.
Mallika ImwongFaculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Charles Woodrow1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Magnus Manske1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK.ORCID 0000000159160947
Jim Stalker1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK.
Eleanor DruryWellcome Trust Sanger Institute, Hinxton, UK.
Susana Campino1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK.
Lucas Amenga-Etego1] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [2] Navrongo Health Research Centre, Navrongo, Ghana.
Thuy-Nhien Nguyen ThanhOxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
Hien Tinh Tran1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [2] Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme, Ho Chi Minh City, Vietnam.
Pascal RingwaldGlobal Malaria Programme, World Health Organization, Geneva, Switzerland.
Delia BethellDepartment of Immunology and Medicine, US Army Medical Component, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS), Bangkok, Thailand.
Francois Nosten1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [3] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Aung Pyae Phyo1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [3] Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Sasithon PukrittayakameeFaculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.ORCID 0000000325733967
Kesinee ChotivanichFaculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Char Meng ChuorNational Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Chea NguonNational Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Seila SuonNational Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Sokunthea SrengNational Center for Parasitology, Entomology and Malaria Control, Phnom Penh, Cambodia.
Paul N Newton1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [2] Lao Oxford Mahosot Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Laos.
Mayfong Mayxay1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [2] Lao Oxford Mahosot Wellcome Trust Research Unit (LOMWRU), Mahosot Hospital, Vientiane, Laos. [3] Faculty of Postgraduate Studies, University of Health Sciences, Vientiane, Laos.
Maniphone KhanthavongCenter of Malariology, Parasitology and Entomology, Ministry of Health, Vientiane, Laos.
Bouasy HongvanthongCenter of Malariology, Parasitology and Entomology, Ministry of Health, Vientiane, Laos.
Ye HtutDepartment of Medical Research, Lower Myanmar, Yangon, Myanmar.
Kay Thwe HanDepartment of Medical Research, Lower Myanmar, Yangon, Myanmar.
Myat Phone KyawDepartment of Medical Research, Lower Myanmar, Yangon, Myanmar.
Md Abul FaizMalaria Research Group and Dev Care Foundation, Dhaka, Bangladesh.
Caterina I Fanello1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Marie Onyamboko1] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK. [2] Kinshasa School of Public Health, Kinshasa, Democratic Republic of the Congo.
Olugbenga A MokuoluDepartment of Paediatrics and Child Health, University of Ilorin, Ilorin, Nigeria.
Christopher G JacobCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Shannon Takala-HarrisonCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Christopher V Plowe1] Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA. [2] Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Nicholas P Day1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Arjen M Dondorp1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Chris C A Spencer1] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Gilean McVean1] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [2] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [3] Department of Statistics, University of Oxford, Oxford, UK.
Rick M FairhurstLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
Nicholas J White1] Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. [2] Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Dominic P Kwiatkowski1] Wellcome Trust Sanger Institute, Hinxton, UK. [2] Medical Research Council (MRC) Centre for Genomics and Global Health, University of Oxford, Oxford, UK. [3] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Wellcome Sanger Institute · GBMahidol University · THUniversity of Oxford · GBCentre for Human Genetics · GBCambodia National Malaria Center · KHUniversity of Maryland, Baltimore · USMyanmar Oxford Clinical Research Unit · MMNational Institutes of Health · USMahosot Hospital · LAMinistry of Health · LAArmed Forces Research Institute of Medical Science · THChild Health Research Foundation · BDOxford University Clinical Research Unit · VNUniversity of Ilorin · NGUniversity of Kinshasa · CDWorld Health Organization · CH
Funding
International Research in Cambodia: Tropical Medicine and Vector Research ZIAAI001066 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI YEK, CHRISTINA · 2009 to 2025
$10.8MMalaria Pathogenesis and Human ImmunityZIAAI001000 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FAIRHURST, RICK · 2009 to 2017
$9.3MGenome-wide studies to identify markers of artemisinin-resistant malariaR01AI101713 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI HARRISON, SHANNON TAKALA · 2013 to 2016
$1.8MHoward Hughes Medical InstituteIntramural NIH HHSMedical Research Council G0600718Medical Research Council MR/M006212/1NIAID NIH HHS R01 AI101713Wellcome Trust 089276Wellcome Trust 090532/Z/09/ZWellcome Trust 090770Wellcome Trust 090770/Z/09/ZWellcome Trust 093956Wellcome Trust 098051World Health Organization 001
Abstract
We report a large multicenter genome-wide association study of Plasmodium falciparum resistance to artemisinin, the frontline antimalarial drug. Across 15 locations in Southeast Asia, we identified at least 20 mutations in kelch13 (PF3D7_1343700) affecting the encoded propeller and BTB/POZ domains, which were associated with a slow parasite clearance rate after treatment with artemisinin derivatives. Nonsynonymous polymorphisms in fd (ferredoxin), arps10 (apicoplast ribosomal protein S10), mdr2 (multidrug resistance protein 2) and crt (chloroquine resistance transporter) also showed strong associations with artemisinin resistance. Analysis of the fine structure of the parasite population showed that the fd, arps10, mdr2 and crt polymorphisms are markers of a genetic background on which kelch13 mutations are particularly likely to arise and that they correlate with the contemporary geographical boundaries and population frequencies of artemisinin resistance. These findings indicate that the risk of new resistance-causing mutations emerging is determined by specific predisposing genetic factors in the underlying parasite population.
Indexed as
Genome, ProtozoanAntimalarialsArtemisininsDrug ResistanceGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMalaria, FalciparumMutationPlasmodium falciparumPolymorphism, Single NucleotideAntimalarialsartemisininArtemisinins
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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.