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Artemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 (pfmdr1) Increased Copy Number Among African Malaria Infections

2025-06-15Artigo científico Acesso aberto
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dc.contributor.authorFançony, Claudia
dc.contributor.authorFortes-Gabriel, Elsa
dc.contributor.authorZage, Félix
dc.contributor.authorAlexiou, Evangelia
dc.contributor.authorBroumou, Ioanna
dc.contributor.authorPernaute-Lau, Leyre
dc.contributor.authorPanzo, Jorge
dc.contributor.authorAntónio, Esperança J.
dc.contributor.authorCristovão, Mario S.
dc.contributor.authorDomingos, José M.
dc.contributor.authorSassoma, Estevão
dc.contributor.authorKuatoko, Fernando
dc.contributor.authorRosario, Edite V. N.
dc.contributor.authorMartins, António
dc.contributor.authorFärnert, Anna
dc.contributor.authorBernardino, Luis
dc.contributor.authorDe Sousa, Tais N.
dc.contributor.authorGil, José Pedro
dc.contributor.institutionIndividual Health Care (IHC)
dc.contributor.institutionGlobal Health and Tropical Medicine (GHTM)
dc.contributor.institutionInstituto de Higiene e Medicina Tropical (IHMT)
dc.contributor.pblOxford University Press
dc.date.accessioned2025-10-01T22:02:44Z
dc.date.available2025-10-01T22:02:44Z
dc.date.issued2025-06-15
dc.descriptionFunding Information: This work was supported by the Agha Kan Development Network, Fundacao para a Ciencia e Tecnologia (FCT) Portugal, and Fundacao Calouste Gulbenkian MalAngo Project; the Swedish Research Council (Vetenskapradet, Stockholm) (grant numbers 2021-05666, 2021-06048, and 2021-03105); and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Brazil (grant number 200075/2022-5). C. F. is the recipient of a Fundacao Calouste Gulbenkian training grant. L. P.-L. was the recipient of a fellowship from the FCT Portugal Biological Systems, Functional, and Integrative Genomics PhD program PD65-2012 (grant number SFRH/BD/142860/2018). Publisher Copyright: © 2025 The Author(s).
dc.description.abstractBackground Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa. Methods An efficacy trial was carried out based on directly observed artemether-lumefantrine therapy at Bengo, Northern Angola. One-hundred Plasmodium falciparum uncomplicated malaria patients (2-10 years old) were enrolled, hospitalized for the treatment period, and followed up for 42 days. Polymerase chain reaction (PCR) correction was performed with pfmsp1/2 plus glurp, with analysis considering 2 or 3 coincident markers. Infections were tested by quantitative PCR (qPCR) for pfmdr1 copy number (pfmdr1×N), a potential P. falciparum marker of lumefantrine resistance previously identified in the region. In vitro clone mixtures were built and used to determine the relation between qPCR copy number scores and actual intrainfection quantitative fractions of pfmdr1×N. Results We observed a significant posttreatment selection of gene amplification, suggesting a role in the parasite in vivo response to this drug. pfmdr1×2 qPCR scores of 1.3, 1.4, and 1.5 were determined to correspond to 15%, 25%, and 35% intrainfection rates. Patients carrying infections with a score ≥1.4 at baseline were linked to decreased artemether-lumefantrine day 42 efficacy (79% vs 97% single-copy pfmdr1). All infections were pfmdr1 N86 carriers and no pfk13 mutations were found. Conclusions Our study suggests pfmdr1×N as a marker of P. falciparum in vivo response to lumefantrine in Africa, while indicating patients carrying infections with a pretreatment pfmdr1×N score ≥1.4 before treatment are a group experiencing decreased artemether-lumefantrine performance.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent760967
dc.identifier.doi10.1093/infdis/jiaf155
dc.identifier.issn0022-1899
dc.identifier.otherPURE: 123206537
dc.identifier.otherPURE UUID: c5893c52-0003-4e8a-82a5-59a0707a6179
dc.identifier.otherScopus: 105010930023
dc.identifier.otherWOS: 001462765400001
dc.identifier.otherPubMed: 40138574
dc.identifier.otherPubMedCentral: PMC12247823
dc.identifier.urihttp://hdl.handle.net/10362/188866
dc.identifier.urlhttps://www.scopus.com/pages/publications/105010930023
dc.language.isoeng
dc.peerreviewedyes
dc.subjectartemether-lumefantrine
dc.subjectdrug resistance
dc.subjectgene copy number
dc.subjectpfmdr1
dc.subjectPlasmodium falciparum malaria
dc.subjectGeneral Medicine
dc.subjectSDG 3 - Good Health and Well-being
dc.titleArtemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 (pfmdr1) Increased Copy Number Among African Malaria Infectionsen
dc.typejournal article
degois.publication.firstPagee1119
degois.publication.issue6
degois.publication.lastPagee1128
degois.publication.titleJournal of Infectious Diseases
degois.publication.volume231
dspace.entity.typePublication
rcaap.rightsopenAccess

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