Evidence map›Paper›PMID 24035558›Full record

ArticleThe Lancet. Infectious diseases2013

Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies.

Benoit Witkowski, Chanaki Amaratunga, Nimol Khim, Sokunthea Sreng, Pheaktra Chim, Saorin Kim, Pharath Lim, Sivanna Mao, Chantha Sopha, Baramey Sam and 8 more

4 registry-linked trialsOpen access · greenAbstract read
In one paragraph

Article in The Lancet. Infectious diseases, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 390 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
390citing papers in PubMed, 3 pooled it
46.0field-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.

NCT00341003 completednot on this map

Multidisciplinary Studies of Severe Malaria and Antimalarial Drug Resistance in Cambodia

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2005 to 2011Enrolled2,090ConditionsSevere Malaria, Malaria, Antimalarial Drug Resistance
NCT01736319 completednot on this map

Artemisinin-resistant Plasmodium Falciparum Malaria in Cambodia

TypeobservationalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2012 to 2016Enrolled561ConditionsPlasmodium Falciparum Malaria
NCT02604966 phase4unknown statusnot on this mapstarted 2015, after this paper: background citation

Efficacy of Artesunate Monotherapy and Dihydroartemisinin - Piperaquine in Patients With Uncomplicated Falciparum Malaria in Central Vietnam

TypeinterventionalSponsorNational Institute of Malariology, Parasitology and Entomology, VietnamRan2015 to 2016Enrolled120ConditionsDrug Resistant Malaria Due to Plasmodium FalciparumArmsArtesunate (AS) group, DHA - PPQ group
NCT03241901 phase4completednot on this mapstarted 2017, after this paper: background citation

"Aiming at Prolonging the Therapeutic Life Span of Artemisinin-based Combination Therapies (ACT) in an Era of Imminent Plasmodium Falciparum Resistance in Bagamoyo District, Tanzania - New Strategies With Old Tools"

TypeinterventionalSponsorMuhimbili University of Health and Allied SciencesRan2017 to 2018Enrolled280ConditionsMalaria,FalciparumArmsArtemether-Lumefantrine Tab 20-120mg, Primaquine Phosphate 0.25 mg/kg, Placebo
3 · Its place in the literature

Who cites it

390 citing papers in PubMed, 3 syntheses or guidelines pooled it, 641 citations in OpenAlex.

  1. Pooled it
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  7. Pharmacokinetics andAntimicrobial agents and chemotherapy · 2020
    Trial
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330 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 3 countries.

Benoit WitkowskiMalaria Molecular Epidemiology Unit, Institut Pasteur du Cambodge, Phnom Penh, Cambodia.
Chanaki Amaratunga
Nimol Khim
Sokunthea Sreng
Pheaktra Chim
Saorin Kim
Pharath Lim
Sivanna Mao
Chantha Sopha
Baramey Sam
Jennifer M Anderson
Socheat Duong
Char Meng Chuor
Walter R J Taylor
Seila Suon
Odile Mercereau-Puijalon
Rick M Fairhurst
Didier Menard
Institut Pasteur du Cambodge · KHCambodia National Malaria Center · KHNational Institutes of Health · USInstitut Pasteur · FRNational Institute of Allergy and Infectious Diseases · 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
Intramural NIH HHS Z99 AI999999
6 · The paper itself

Abstract

backgroundArtemisinin resistance in Plasmodium falciparum lengthens parasite clearance half-life during artemisinin monotherapy or artemisinin-based combination therapy. Absence of in-vitro and ex-vivo correlates of artemisinin resistance hinders study of this phenotype. We aimed to assess whether an in-vitro ring-stage survival assay (RSA) can identify culture-adapted P falciparum isolates from patients with slow-clearing or fast-clearing infections, to investigate the stage-dependent susceptibility of parasites to dihydroartemisinin in the in-vitro RSA, and to assess whether an ex-vivo RSA can identify artemisinin-resistant P falciparum infections.

methodsWe culture-adapted parasites from patients with long and short parasite clearance half-lives from a study done in Pursat, Cambodia, in 2010 (registered with ClinicalTrials.gov, number NCT00341003) and used novel in-vitro survival assays to explore the stage-dependent susceptibility of slow-clearing and fast-clearing parasites to dihydroartemisinin. In 2012, we implemented the RSA in prospective parasite clearance studies in Pursat, Preah Vihear, and Ratanakiri, Cambodia (NCT01736319), to measure the ex-vivo responses of parasites from patients with malaria. Continuous variables were compared with the Mann-Whitney U test. Correlations were analysed with the Spearman correlation test.

findingsIn-vitro survival rates of culture-adapted parasites from 13 slow-clearing and 13 fast-clearing infections differed significantly when assays were done on 0-3 h ring-stage parasites (10·88% vs 0·23%; p=0·007). Ex-vivo survival rates significantly correlated with in-vivo parasite clearance half-lives (n=30, r=0·74, 95% CI 0·50-0·87; p<0·0001).

interpretationThe in-vitro RSA of 0-3 h ring-stage parasites provides a platform for the molecular characterisation of artemisinin resistance. The ex-vivo RSA can be easily implemented where surveillance for artemisinin resistance is needed.

fundingInstitut Pasteur du Cambodge and the Intramural Research Program, NIAID, NIH.

Indexed as

AntimalarialsArtemisininsCambodiaDrug ResistanceGenotypeHumansMalaria, FalciparumPhenotypePlasmodium falciparumProspective StudiesSurvival AnalysisSurvival RateAntimalarialsArtemisininsartenimol

Identifiers

PMID24035558
PMCPMC5015432
OpenAlexW2129428401

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.