Evidence map›Paper›PMID 27596849›Full record

Trial reportMalaria journal2016

Selection of Plasmodium falciparum pfcrt and pfmdr1 polymorphisms after treatment with artesunate-amodiaquine fixed dose combination or artemether-lumefantrine in Liberia.

Sabina Dahlström Otienoburu, Oumou Maïga-Ascofaré, Birgit Schramm, Vincent Jullien, Joel J Jones, Yah M Zolia, Pascal Houzé, Elizabeth A Ashley, Jean-René Kiechel, Philippe J Guérin and 2 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in Malaria journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 3 pooled it
3.6field-weighted citation impact, top 7% 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

37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 65 citations in OpenAlex.

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  9. Tracking Drug Resistance inInternational journal of molecular sciences · 2025
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  12. Evolution of Plasmodium falciparum antimalarial drug resistance markers post-adoption of artemisinin-based combination therapies in Yaounde, Cameroon.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2023
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  14. Drug Resistance Molecular Markers ofTropical medicine and infectious disease · 2023
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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

12 authors at 8 institutions in 6 countries.

Sabina Dahlström OtienoburuInstitut de Médecine et d'Epidémiologie Appliquée, Bichat-C. Bernard Hospital, Paris, France. sabina.dahlstrom@gmail.com.ORCID 0000-0001-5042-7924
Oumou Maïga-AscofaréInstitut de Médecine et d'Epidémiologie Appliquée, Bichat-C. Bernard Hospital, Paris, France.
Birgit SchrammEpicentre, 75012, Paris, France.
Vincent JullienINSERM U1129, Service de Pharmacologie, Hôpital Européen Georges Pompidou, Université Paris Descartes, 75015, Paris, France.
Joel J JonesNational Malaria Control Programme, Ministry of Health and Social Welfare, Monrovia, Liberia.
Yah M ZoliaNational Malaria Control Programme, Ministry of Health and Social Welfare, Monrovia, Liberia.
Pascal HouzéAP-HP, Saint-Louis Hospital Biochemistry Laboratory, Paris, France.
Elizabeth A AshleyEpicentre, 75012, Paris, France.
Jean-René KiechelDrugs for Neglected Diseases Initiative, Geneva, Switzerland.
Philippe J GuérinWorldWide Antimalarial Resistance Network, Oxford, UK.
Jacques Le BrasInstitut de Médecine et d'Epidémiologie Appliquée, Bichat-C. Bernard Hospital, Paris, France.
Sandrine HouzéIRD UMR216, Paris-Descartes University, Paris, France.
Délégation Paris 5 · FRMinistry of Health and Social Welfare · LRUniversity of Oxford · GBAssistance Publique – Hôpitaux de Paris · FRDrugs for Neglected Diseases Initiative · CHInserm · FRInstitut de Médecine et d'Epidémiologie Africaines · FRJohnson C. Smith University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlasmodium falciparum uncomplicated malaria can successfully be treated with an artemisinin-based combination therapy (ACT). However resistance is spreading to the different ACT compounds; the artemisinin derivative and the partner drug. Studies of P. falciparum polymorphisms associated with drug resistance can provide a useful tool to track resistance and guide treatment policy as well as an in-depth understanding of the development and spread of resistance.

methodsThe role of P. falciparum molecular markers in selection of reinfections was assessed in an efficacy trial comparing artesunate-amodiaquine fixed-dose combination with artemether-lumefantrine to treat malaria in Nimba County, Liberia 2008-2009. P. falciparum polymorphisms in pfcrt 76, pfmdr1 86, 184 and 1246, and pfmrp1 876 and 1466 were analysed by PCR-RFLP and pyrosequencing.

resultsHigh baseline prevalence of pfmdr1 1246Y was found in Nimba county (38 %). Pfmdr1 1246Y and pfmdr1 86+184+1246 haplotypes NYY and YYY were selected in reinfections in the artesunate-amodiaquine arm and pfcrt K76, pfmdr1 N86 and pfmdr1 haplotype NFD were selected in artemether-lumefantrine reinfections. Parasites harbouring pfmdr1 1246Y could reinfect earlier after treatment with artesunate-amodiaquine and parasites carrying pfmdr1 N86 could reinfect at higher lumefantrine concentrations in patients treated with artemether-lumefantrine.

conclusionsAlthough treatment is highly efficacious, selection of molecular markers in reinfections could indicate a decreased sensitivity or tolerance of parasites to the current treatments and the baseline prevalence of molecular markers should be closely monitored. Since individual drug levels and the day of reinfection were demonstrated to be key determinants for selection of reinfections, this data needs to be collected and taken into account for accurate evaluation of molecular markers for anti-malarial treatments. The protocols for the clinical trial was registered with Current Controlled Trials, under the Identifier Number ISRCTN51688713 on 9 October 2008.

Indexed as

AmodiaquineAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsATP-Binding Cassette, Sub-Family C ProteinsChild, PreschoolDNA, ProtozoanDrug CombinationsDrug ResistanceEthanolaminesFluorenesGenotypeHumansInfantLiberiaMalaria, FalciparumAmodiaquineamodiaquine, artesunate drug combinationAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsATP-Binding Cassette, Sub-Family C ProteinsDNA, ProtozoanDrug CombinationsEthanolaminesFluorenesMdr1 protein, Plasmodium falciparumMembrane Transport ProteinsPfCRT protein, Plasmodium falciparumProtozoan ProteinsAntimalarial agentsArtemisinin-based combination therapyDrug resistanceMalariapfcrtpfmdr1pfmrp1Plasmodium falciparumSelection

Identifiers

PMID27596849
PMCPMC5011943
OpenAlexW2508762646

What OpenQuestion holds

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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.