Evidence map›Paper›PMID 28494763›Full record

ArticleMalaria journal2017

Artemisinin resistance without pfkelch13 mutations in Plasmodium falciparum isolates from Cambodia.

Angana Mukherjee, Selina Bopp, Pamela Magistrado, Wesley Wong, Rachel Daniels, Allison Demas, Stephen Schaffner, Chanaki Amaratunga, Pharath Lim, Mehul Dhorda and 8 more

Open access · goldAbstract read
In one paragraph

Article in Malaria journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
16.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Competitive suppression and release in artemisinin-resistantEvolution, medicine, and public health · 2026
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  11. Global assessment of partial artemisinin resistance: multicenter trial across Kenya, Peru, and Thailand in patients with uncomplicated Plasmodium falciparum malaria.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2025
    Article
  12. Article
  13. A NovelmedRxiv : the preprint server for health sciences · 2025
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  14. Artemisinin pressure in field isolates can select highly resistantAntimicrobial agents and chemotherapy · 2025
    Article
  15. Epidemiology, Detection and Treatment of Malaria.Tropical medicine and infectious disease · 2024
    Article
  16. Article
  17. Putative molecular markers ofFrontiers in epidemiology · 2024
    Article
  18. Article
  19. Article
  20. Review

18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 4 countries.

Angana MukherjeeDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Selina BoppDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Pamela MagistradoDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Wesley WongDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Rachel DanielsDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Allison DemasDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Stephen SchaffnerInfectious Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Chanaki AmaratungaLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Pharath LimLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Mehul DhordaAsia Regional Centre, Worldwide Antimalarial Resistance Network, Bangkok, Thailand.
Olivo MiottoMahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
Charles WoodrowNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Elizabeth A AshleyNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Arjen M DondorpNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Nicholas J WhiteNuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, UK.
Dyann WirthDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA.
Rick FairhurstLaboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Sarah K VolkmanDepartment of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health, 665 Huntington Avenue, I-704, Boston, MA, 02115, USA. svolkman@hsph.harvard.edu.
Harvard University · USMahidol Oxford Tropical Medicine Research Unit · THBroad Institute · USNational Institute of Allergy and Infectious Diseases · USNational Institutes of Health · US

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
$10.8M
Malaria Pathogenesis and Human ImmunityZIAAI001000 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI FAIRHURST, RICK · 2009 to 2017
$9.3M
Novel Genetic Mechanism of Artemisinin Resistance for MalariaR01AI099105 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HARTL, DANIEL L, WIRTH, DYANN F · 2013 to 2021
$5.4M
6 · The paper itself

Abstract

backgroundArtemisinin resistance is associated with delayed parasite clearance half-life in vivo and correlates with ring-stage survival under dihydroartemisinin in vitro. Both phenotypes are associated with mutations in the PF3D7_1343700 pfkelch13 gene. Recent spread of artemisinin resistance and emerging piperaquine resistance in Southeast Asia show that artemisinin combination therapy, such as dihydroartemisinin-piperaquine, are losing clinical effectiveness, prompting investigation of drug resistance mechanisms and development of strategies to surmount emerging anti-malarial resistance.

methodsSixty-eight parasites isolates with in vivo clearance data were obtained from two Tracking Resistance to Artemisinin Collaboration study sites in Cambodia, culture-adapted, and genotyped for pfkelch13 and other mutations including pfmdr1 copy number; and the RSA

resultsAmong these 36 parasites one isolate demonstrated increased ring-stage survival for a PfKelch13 mutation (D584V, RSA

conclusionsThis study of 68 culture-adapted Plasmodium falciparum clinical isolates from Cambodia with known clearance values, associated the D584V PfKelch13 mutation with increased ring-stage survival and identified parasites that lack pfkelch13 mutations yet exhibit increased ring-stage survival. These data suggest mutations other than those found in pfkelch13 may be involved in conferring artemisinin resistance in P. falciparum. Piperaquine resistance was also detected among the same Cambodian samples, consistent with reports of emerging piperaquine resistance in the field. These culture-adapted parasites permit further investigation of mechanisms of both artemisinin and piperaquine resistance and development of strategies to prevent or overcome anti-malarial resistance.

Indexed as

Drug ResistanceAntimalarialsArtemisininsCambodiaMutationPlasmodium falciparumProtozoan ProteinsAntimalarialsartemisininArtemisininsProtozoan ProteinsArtemisinin resistancepfkelch13Piperaquine resistancePlasmodium falciparum

Identifiers

PMID28494763
PMCPMC5427620
OpenAlexW2613173822

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

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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.