| Author | Fançony, Claudia | |
| Author | Fortes-Gabriel, Elsa | |
| Author | Zage, Félix | |
| Author | Alexiou, Evangelia | |
| Author | Broumou, Ioanna | |
| Author | Pernaute-Lau, Leyre | |
| Author | Panzo, Jorge | |
| Author | António, Esperança J | |
| Author | Cristovão, Mario S | |
| Author | Domingos, José M | |
| Author | Sassoma, Estevão | |
| Author | Kuatoko, Fernando | |
| Author | Rosario, Edite V N | |
| Author | Martins, António | |
| Author | Färnert, Anna | |
| Author | Bernardino, Luis | |
| Author | Sousa, Tais Nobrega de | |
| Author | Gil, José Pedro | |
| Access date | 2025-04-30T19:03:10Z | |
| Available date | 2025-04-30T19:03:10Z | |
| Document date | 2025 | |
| Citation | 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. | en_US |
| ISSN | 0022-1899 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/70059 | |
| Language | eng | en_US |
| Publisher | Oxford University Press | en_US |
| Rights | open access | en_US |
| Title | Artemether-Lumefantrine treatment selects Plasmodium falciparum multidrug resistance 1 (pfmdr1) increased copy number among African malaria infections. | en_US |
| Type | Article | en_US |
| DOI | 10.1093/infdis/jiaf155 | |
| Abstract | 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. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. / Instituto Superior Técnico Militar. Luanda, Angola | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet. Stockholm, Sweden. | en_US |
| Affilliation | Department of Medicine Solna. Karolinska Institutet. Stockholm, Sweden. | en_US |
| Affilliation | Department of Microbiology, Tumor and Cell Biology. Karolinska Institutet. Stockholm, Sweden. / The Art of Discovery. Derio. Basque Country, Spain. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. / Universidade Agostinho Neto. Faculdade de Medicina. Luanda, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. / Universidade Agostinho Neto. Faculdade de Medicina. Luanda, Angola. | en_US |
| Affilliation | Centro de Investigação em Saúde de Angola. Instituto Nacional de Investigação em Saúde. Caxito, Angola. | en_US |
| Affilliation | Ministerio da Saude. Centro de Saude Materno Infantil das Mabubas. Mabubas, Angola. | en_US |
| Affilliation | Department of Medicine Solna. Karolinska Institutet. Stockholm, Sweden. / Department of Infectious Diseases. Karolinska University hospital. Stockholm, Sweden. | en_US |
| Affilliation | Hospital Pediátrico David Bernardino, Luanda, Angola. | en_US |
| Affilliation | 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. | en_US |
| Affilliation | 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. | en_US |
| Subject | Plasmodium falciparum malaria | en_US |
| Subject | Pfmdr1 | en_US |
| Subject | Artemether-lumefantrine. | en_US |
