{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:54:53Z","timestamp":1776408893958,"version":"3.51.2"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Agha Kan Development"},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia"},{"name":"Portugal"},{"DOI":"10.13039\/501100000348","name":"Funda\u00e7\u00e3o Calouste Gulbenkian","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vetenskapr\u00e5det","award":["2021\u201305666"],"award-info":[{"award-number":["2021\u201305666"]}]},{"name":"Vetenskapr\u00e5det","award":["2021-06048"],"award-info":[{"award-number":["2021-06048"]}]},{"name":"Vetenskapr\u00e5det","award":["2021-03105"],"award-info":[{"award-number":["2021-03105"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["200075\/2022-5"],"award-info":[{"award-number":["200075\/2022-5"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006129","name":"FCT","doi-asserted-by":"publisher","award":["SFRH\/BD\/142860\/2018"],"award-info":[{"award-number":["SFRH\/BD\/142860\/2018"]}],"id":[{"id":"10.13039\/100006129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u201310 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\u00d7N), 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\u00d7N.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed a significant posttreatment selection of gene amplification, suggesting a role in the parasite in vivo response to this drug. pfmdr1\u00d72 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 \u22651.4 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study suggests pfmdr1\u00d7N as a marker of P. falciparum in vivo response to lumefantrine in Africa, while indicating patients carrying infections with a pretreatment pfmdr1\u00d7N score \u22651.4 before treatment are a group experiencing decreased artemether-lumefantrine performance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiaf155","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T08:17:57Z","timestamp":1744273077000},"page":"e1119-e1128","source":"Crossref","is-referenced-by-count":6,"title":["Artemether-Lumefantrine Treatment Selects <i>Plasmodium falciparum<\/i> Multidrug Resistance 1 (<i>pfmdr1<\/i>) Increased Copy Number Among African Malaria Infections"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-1769","authenticated-orcid":false,"given":"Claudia","family":"Fan\u00e7ony","sequence":"first","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9378-3643","authenticated-orcid":false,"given":"Elsa","family":"Fortes-Gabriel","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]},{"name":"Instituto Superior T\u00e9cnico Militar , Luanda ,","place":["Angola"]}]},{"given":"F\u00e9lix","family":"Zage","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"given":"Evangelia","family":"Alexiou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-3820","authenticated-orcid":false,"given":"Ioanna","family":"Broumou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Solna, Karolinska Institutet , Stockholm ,","place":["Sweden"]}]},{"given":"Leyre","family":"Pernaute-Lau","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"The Art of Discovery , Derio, Basque Country ,","place":["Spain"]}]},{"given":"Jorge","family":"Panzo","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"given":"Esperan\u00e7a J","family":"Ant\u00f3nio","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"given":"Mario S","family":"Cristov\u00e3o","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"given":"Jos\u00e9 M","family":"Domingos","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"given":"Estev\u00e3o","family":"Sassoma","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]},{"name":"Faculdade de Medicina, Universidade Agostinho Neto , Luanda ,","place":["Angola"]}]},{"given":"Fernando","family":"Kuatoko","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]},{"name":"Faculdade de Medicina, Universidade Agostinho Neto , Luanda ,","place":["Angola"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0419-6181","authenticated-orcid":false,"given":"Edite V N","family":"Rosario","sequence":"additional","affiliation":[{"name":"Centro de Investiga\u00e7\u00e3o em Sa\u00fade de Angola, Instituto Nacional de Investiga\u00e7\u00e3o em Sa\u00fade , Caxito ,","place":["Angola"]}]},{"given":"Ant\u00f3nio","family":"Martins","sequence":"additional","affiliation":[{"name":"Centro de Saude Materno Infantil das Mabubas, Ministerio da Saude , Mabubas ,","place":["Angola"]}]},{"given":"Anna","family":"F\u00e4rnert","sequence":"additional","affiliation":[{"name":"Department of Medicine, Solna, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Department of Infectious Diseases, Karolinska University Hospital , Stockholm ,","place":["Sweden"]}]},{"given":"Luis","family":"Bernardino","sequence":"additional","affiliation":[{"name":"Hospital Pedi\u00e1trico David Bernardino , Luanda ,","place":["Angola"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6874-9427","authenticated-orcid":false,"given":"Tais N","family":"de Sousa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Molecular Biology and Malaria Immunology Research Group, Instituto Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz , Belo Horizonte ,","place":["Brazil"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6107-9379","authenticated-orcid":false,"given":"Jos\u00e9 Pedro","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor, and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Clinical Tropical Medicine, Global Health, and Tropical Medicine, Institute of Hygiene and Tropical Medicine, Nova University of Lisbon , Lisbon ,","place":["Portugal"]}]}],"member":"286","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"2025071111130548600_jiaf155-B1","doi-asserted-by":"crossref","first-page":"e01949-20","DOI":"10.1128\/AAC.01949-20","article-title":"Continued low efficacy of artemether-lumefantrine in Angola in 2019","volume":"65","author":"Dimbu","year":"2021","journal-title":"Antimicrob Agents 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