Evidence map›Paper›PMID 30967148›Full record

Trial reportMalaria journal2019

African isolates show a high proportion of multiple copies of the Plasmodium falciparum plasmepsin-2 gene, a piperaquine resistance marker.

Didier Leroy, Fiona Macintyre, Yeka Adoke, Serge Ouoba, Aissata Barry, Ghyslain Mombo-Ngoma, Jacques Mari Ndong Ngomo, Rosauro Varo, Yannelle Dossou, Antoinette Kitoto Tshefu and 7 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIRandomized Controlled Trial
In one paragraph

Trial report in Malaria journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02083380 (Randomised Phase IIb Study of Efficacy, Safety, Tolerability & Pharmacokinetics of a Single Dose Regimen of Artefenomel), which is not on this map. Cited by 29 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 6 pooled it
6.0field-weighted citation impact, top 4% 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.

NCT02083380 phase2 / phase3completednot on this map

Randomised Phase IIb Study of Efficacy, Safety, Tolerability & Pharmacokinetics of a Single Dose Regimen of Artefenomel (OZ439) in Loose Combination With Piperaquine in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria.

TypeinterventionalSponsorMedicines for Malaria VentureRan2014 to 2015Enrolled448ConditionsUncomplicated Plasmodium Falciparum MalariaArmsArtefenomel 800mg: piperaquine 640mg, Artefenomel 800mg: piperaquine 960mg, Artefenomel 800mg: piperaquine 1440mg
3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 6 syntheses or guidelines pooled it, 47 citations in OpenAlex.

  1. Pooled it
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  4. Mapping Antimalarial Drug Resistance in Mozambique: A Systematic Review ofInternational journal of molecular sciences · 2024
    Pooled it
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  7. A Multidimensional Analysis of the Bimodal Piperaquine Response inbioRxiv : the preprint server for biology · 2026
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  20. Drug Resistance Molecular Markers ofTropical medicine and infectious disease · 2023
    Article
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

17 authors at 11 institutions in 12 countries.

Didier LeroyMedicines for Malaria Venture, Geneva, Switzerland. leroyd@mmv.org.ORCID http://orcid.org/0000-0002-5594-3204
Fiona MacintyreMedicines for Malaria Venture, Geneva, Switzerland.
Yeka AdokeInfectious Diseases Research Collaboration, Tororo Hospital, Tororo, Uganda.
Serge OuobaInstitut de Recherche en Sciences de la Santé - Unité de Recherche Clinique de Nanoro, Ouagadougou, Burkina Faso.
Aissata BarryInstitut de Recherche en Sciences de la Santé - Unité de Recherche Clinique de Nanoro, Ouagadougou, Burkina Faso.
Ghyslain Mombo-NgomaCentre de Recherches Médicales de Lambaréné, Lambaréné, Gabon.
Jacques Mari Ndong NgomoDépartement de Parasitologie, Université des Sciences de la Santé Gabon, Libreville, Gabon.
Rosauro VaroISGlobal, Barcelona Ctr. Int. Health Res. (CRESIB), Hospital Clínic - Universitat de Barcelona, Barcelona, Spain.
Yannelle DossouCentre de Recherche sur le Paludisme Associé à la Grossesse et l'Enfance, Faculté Des Sciences De La Santé, Cotonou, Benin.
Antoinette Kitoto TshefuCentre de Recherche du Centre Hospitalier de Mont Amba, Kinshasa School of Public Health, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
Tran Thanh DuongNational Institute of Malariology, Parasitology and Entomology, Hanoi, Vietnam.
Bui Quang PhucClinical Pharmaceutical Research Department, National Institute of Malariology, Parasitology and Entomology, 35 Trung Van Street, Nam Tu Liem District, Hanoi, Vietnam.
Bart LaurijssensBEL Pharm Consulting, Nîmes, France.
Roland KlopperClindata Pty Ltd, Bloemfontein, South Africa.
Nimol KhimMalaria Molecular Epidemiology Unit, Institut Pasteur in Cambodia, Phnom Penh, Cambodia.
Eric LegrandMalaria Genetics and Resistance Group, INSERM U1201-CNRS ERL919, Institut Pasteur, Paris, France.
Didier MénardMalaria Genetics and Resistance Group, INSERM U1201-CNRS ERL919, Institut Pasteur, Paris, France. dmenard@pasteur.fr.
Centre National de la Recherche Scientifique · FRInstitut de Recherche en Sciences de la Santé · BFMedicines for Malaria Venture · CHNational Institute of Malariology, Parasitology and Entomology · VNCentre de Recherche Médicales de Lambaréné · GAInfectious Diseases Research Collaboration · UGInstitució Catalana de Recerca i Estudis Avançats · ESInstitut Pasteur du Cambodge · KHMinistre de la Santé · BJUniversité des Sciences de la Santé · GAUniversity of Kinshasa · CD

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundToday, the development of new and well-tolerated anti-malarial drugs is strongly justified by the emergence of Plasmodium falciparum resistance. In 2014-2015, a phase 2b clinical study was conducted to evaluate the efficacy of a single oral dose of Artefenomel (OZ439)-piperaquine (PPQ) in Asian and African patients presenting with uncomplicated falciparum malaria.

methodsBlood samples collected before treatment offered the opportunity to investigate the proportion of multidrug resistant parasite genotypes, including P. falciparum kelch13 mutations and copy number variation of both P. falciparum plasmepsin 2 (Pfpm2) and P. falciparum multidrug resistance 1 (Pfmdr1) genes.

resultsValidated kelch13 resistance mutations including C580Y, I543T, P553L and V568G were only detected in parasites from Vietnamese patients. In Africa, isolates with multiple copies of the Pfmdr1 gene were shown to be more frequent than previously reported (21.1%, range from 12.4% in Burkina Faso to 27.4% in Uganda). More strikingly, high proportions of isolates with multiple copies of the Pfpm2 gene, associated with piperaquine (PPQ) resistance, were frequently observed in the African sites, especially in Burkina Faso and Uganda (> 30%).

conclusionsThese findings were considered to sharply contrast with the recent description of increased sensitivity to PPQ of Ugandan parasite isolates. This emphasizes the necessity to investigate in vitro susceptibility profiles to PPQ of African isolates with multiple copies of the Pfpm2 gene and estimate the risk of development of PPQ resistance in Africa. Trial registration Clinicaltrials.gov reference: NCT02083380. Study title: Phase II efficacy study of artefenomel and piperaquine in adults and children with P. falciparum malaria. https://clinicaltrials.gov/ct2/results?cond=&term=NCT02083380&cntry=&state=&city=&dist= . FSFV: 23-Jul-2014; LSLV: 09-Oct-2015.

Indexed as

AdamantaneAdolescentAdultAfricaAgedAntimalarialsAspartic Acid EndopeptidasesBiomarkersChildChild, PreschoolDNA Copy Number VariationsDrug CombinationsDrug ResistanceFemaleGenotypeHumansAdamantaneAntimalarialsartefenomelAspartic Acid EndopeptidasesBiomarkersDrug CombinationsPeroxidespiperaquinePiperazinesplasmepsin IIProtozoan ProteinsQuinolines

Identifiers

PMID30967148
PMCPMC6457011
OpenAlexW2941790884

What OpenQuestion holds

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LicenceCC BY
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.