Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.

Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.

Detalles Bibliográficos
Autores: Fançony, Claudia, Fortes-Gabriel, Elsa, Zage, Félix, Alexiou, Evangelia, Broumou, Ioanna, Pernaute-Lau, Leyre, Panzo, Jorge, António, Esperança J., Cristovão, Mario S., Domingos, José M., Sassoma, Estevão, Kuatoko, Fernando, Rosario, Edite V. N., Martins, António, Färnert, Anna, Bernardino, Luis, Sousa, Taís Nóbrega de, Gil, José Pedro
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:Brasil
Institución:Fundação Oswaldo Cruz (FIOCRUZ)
Repositorio:Repositório Institucional da FIOCRUZ (ARCA)
Idioma:inglés
OAI Identifier:oai:arca.fiocruz.br:icict/70059
Acceso en línea:https://arca.fiocruz.br/handle/icict/70059
Access Level:acceso abierto
Palabra clave:Plasmodium falciparum malaria
Pfmdr1
Artemether-lumefantrine
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dc.title.none.fl_str_mv Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
title Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
spellingShingle Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
Fançony, Claudia
Plasmodium falciparum malaria
Pfmdr1
Artemether-lumefantrine
title_short Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
title_full Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
title_fullStr Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
title_full_unstemmed Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
title_sort Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.
dc.creator.none.fl_str_mv Fançony, Claudia
Fortes-Gabriel, Elsa
Zage, Félix
Alexiou, Evangelia
Broumou, Ioanna
Pernaute-Lau, Leyre
Panzo, Jorge
António, Esperança J.
Cristovão, Mario S.
Domingos, José M.
Sassoma, Estevão
Kuatoko, Fernando
Rosario, Edite V. N.
Martins, António
Färnert, Anna
Bernardino, Luis
Sousa, Taís Nóbrega de
Gil, José Pedro
author Fançony, Claudia
author_facet Fançony, Claudia
Fortes-Gabriel, Elsa
Zage, Félix
Alexiou, Evangelia
Broumou, Ioanna
Pernaute-Lau, Leyre
Panzo, Jorge
António, Esperança J.
Cristovão, Mario S.
Domingos, José M.
Sassoma, Estevão
Kuatoko, Fernando
Rosario, Edite V. N.
Martins, António
Färnert, Anna
Bernardino, Luis
Sousa, Taís Nóbrega de
Gil, José Pedro
author_role author
author2 Fortes-Gabriel, Elsa
Zage, Félix
Alexiou, Evangelia
Broumou, Ioanna
Pernaute-Lau, Leyre
Panzo, Jorge
António, Esperança J.
Cristovão, Mario S.
Domingos, José M.
Sassoma, Estevão
Kuatoko, Fernando
Rosario, Edite V. N.
Martins, António
Färnert, Anna
Bernardino, Luis
Sousa, Taís Nóbrega de
Gil, José Pedro
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.en.none.fl_str_mv Plasmodium falciparum malaria
Pfmdr1
Artemether-lumefantrine
topic Plasmodium falciparum malaria
Pfmdr1
Artemether-lumefantrine
description Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-04-30T19:03:10Z
dc.date.available.fl_str_mv 2025-04-30T19:03:10Z
dc.date.issued.fl_str_mv 2025
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv FANCONY, Cláudia et al. Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections. The Journal of infectious diseases, 2025 Mar 26 (Epub 2025 Mar 26) 2025.
dc.identifier.uri.fl_str_mv https://arca.fiocruz.br/handle/icict/70059
dc.identifier.issn.none.fl_str_mv 0022-1899
dc.identifier.doi.none.fl_str_mv 10.1093/infdis/jiaf155
identifier_str_mv FANCONY, Cláudia et al. Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections. The Journal of infectious diseases, 2025 Mar 26 (Epub 2025 Mar 26) 2025.
0022-1899
10.1093/infdis/jiaf155
url https://arca.fiocruz.br/handle/icict/70059
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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spelling 2025-04-30T19:03:10Z2025-04-30T19:03:10Z2025FANCONY, Cláudia et al. Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections. The Journal of infectious diseases, 2025 Mar 26 (Epub 2025 Mar 26) 2025.0022-1899https://arca.fiocruz.br/handle/icict/7005910.1093/infdis/jiaf155engOxford University PressArtemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleCentro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. / Instituto Superior Técnico Militar. Luanda, AngolaCentro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet. Stockholm, Sweden.Department of Medicine Solna. Karolinska Institutet. Stockholm, Sweden.Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet. Stockholm, Sweden. / The Art of Discovery. Derio. Basque Country, Spain.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. / Universidade Agostinho Neto. Faculdade de Medicina. Luanda, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. / Universidade Agostinho Neto. Faculdade de Medicina. Luanda, Angola.Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola.Ministerio da Saude. Centro de Saude Materno Infantil das Mabubas. Mabubas, Angola.Department of Medicine Solna. Karolinska Institutet. Stockholm, Sweden. / Department of Infectious Diseases. Karolinska University hospital. Stockholm, Sweden.Hospital Pediátrico David Bernardino, Luanda, Angola.Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet. Stockholm, Sweden. / Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Biologia Molecular e Imunologia da Malária. Belo Horizonte, MG, Brasil.Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet. Stockholm, Sweden. / Clinical Tropical Medicine. Global Health and Tropical Medicine. Institute of Hygiene and Tropical Medicine. Nova University of Lisbon. Lisbon, Portugal.Background: Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa. Methods: An efficacy trial based on directly observed artemether-lumefantrine therapy at Bengo, Northern Angola. 100 Plasmodium falciparum uncomplicated malaria patients (2-10 year-old) were enrolled, hospitalized for the treatment period, and followed up for 42 days. PCR correction was performed with pfmsp1/2 + glurp, with analysis considering 2 or 3 coincident markers. Infections were tested by qPCR for pfmdr1 copy number (pfmdr1xN), a potential Plasmodium 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 intra-infection quantitative fractions of pfmdr1xN. Results: We observed a significant post-treatment selection of gene amplification, suggesting a role in the parasite in vivo response to this drug. pfmdr1x2 qPCR scores of 1.3, 1.4 and 1.5 were determined to correspond to 15%, 25% and 35% intra-infection rates. Patients carrying infections with a score ≥1.4 at baseline were linked to decreased AL 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 pfmdr1xN as a marker of P. falciparum in vivo response to lumefantrine in Africa, while pointing for patients carrying infections with a pre-treatment pfmdr1xN score ≥1.4 before treatment as a group experiencing decreased artemether-lumefantrine performance.Plasmodium falciparum malariaPfmdr1Artemether-lumefantrineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZFançony, ClaudiaFortes-Gabriel, ElsaZage, FélixAlexiou, EvangeliaBroumou, IoannaPernaute-Lau, LeyrePanzo, JorgeAntónio, Esperança J.Cristovão, Mario S.Domingos, José M.Sassoma, EstevãoKuatoko, FernandoRosario, Edite V. 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