| Title: |
Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda |
| Authors: |
Uwimana, Aline; Legrand, Eric; Stokes, Barbara; Ndikumana, Jean-Louis Mangala; Warsame, Marian; Umulisa, Noella; Ngamije, Daniel; Munyaneza, Tharcisse; Mazarati, Jean-Baptiste; Munguti, Kaendi; Campagne, Pascal; Criscuolo, Alexis; Ariey, Frederic; Murindahabi, Monique; Ringwald, Pascal; Fidock, David; Mbituyumuremyi, Aimable; Ménard, Didier |
| Contributors: |
Rwanda Biomedical Center (RBC); Génétique du paludisme et résistance - Malaria Genetics and Resistance; Institut Pasteur Paris (IP); Columbia University Irving Medical Center (CUIMC); Göteborgs Universitet = University of Gothenburg (GU); Johns Hopkins University Baltimore (JHU); Ministry of Health Rwanda; U.S. President’s Malaria Initiative Antananarivo (PMI); U.S. President's Malaria Initiative Atlanta, GA; Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB; Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS); Institut Cochin (IC UM3 (UMR 8104 / U1016)); Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); Columbia University Medical Center (CUMC); Columbia University New York; Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions; Institut Pasteur Paris (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); This work was supported by the World Bank through the East African Public Health Laboratory Networking Project (A.U., JL.M.N., A.M., T.M. and JB.M.), the Bill and Melinda Gates Foundation through the World Health Organization (grant OPP1140599, D.M. and P.R.), the US Department of Defense W81XWH-19-1-0086 (D.A.F.) and the National Institutes of Health R01 AI109023 (D.A.F.).; This work used the computational and storage services (TARS cluster) provided by the IT department at Institut Pasteur, Paris. We thank all patients who contributed samples and their guardians in the communities of the Kicukiro (Masaka), Bugesera (Ruhuha), Rusizi (Bugarama), Gisagara (Kibirizi), Nyagatare (Nyarurema) and Kayonza (Rukara) and all team members in the health centers. We are also grateful to the members of the Malaria and Other Parasitic Diseases Division at the Rwanda Biomedical Center for their support. We acknowledge L. Duval (National Museum of Natural History, Paris) who furnished the probes for Plasmodium DNA capture and B. Izac who performed Illumina sequencing. We also thank B. Menu, C. Gicquel, N. Jolly, M. Ait Ahmed, V. Pirard and S. Ouchhi (Institut Pasteur, Paris) for their support.; ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011) |
| Source: |
ISSN: 1078-8956. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2020 |
| Subject Terms: |
[SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology |
| Description: |
International audience ; Artemisinin resistance (delayed P. falciparum clearance following artemisinin-based combination therapy), is widespread across Southeast Asia but to date has not been reported in Africa1-4. Here we genotyped the P. falciparum K13 (Pfkelch13) propeller domain, mutations in which can mediate artemisinin resistance5,6, in pretreatment samples collected from recent dihydroarteminisin-piperaquine and artemether-lumefantrine efficacy trials in Rwanda7. While cure rates were >95% in both treatment arms, the Pfkelch13 R561H mutation was identified in 19 of 257 (7.4%) patients at Masaka. Phylogenetic analysis revealed the expansion of an indigenous R561H lineage. Gene editing confirmed that this mutation can drive artemisinin resistance in vitro. This study provides evidence for the de novo emergence of Pfkelch13-mediated artemisinin resistance in Rwanda, potentially compromising the continued success of antimalarial chemotherapy in Africa. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/32747827; PUBMED: 32747827 |
| DOI: |
10.1038/s41591-020-1005-2 |
| Availability: |
https://pasteur.hal.science/pasteur-02911712; https://pasteur.hal.science/pasteur-02911712v1/document; https://pasteur.hal.science/pasteur-02911712v1/file/s41591-020-1005-2.pdf; https://doi.org/10.1038/s41591-020-1005-2 |
| Rights: |
http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.9E07521C |
| Database: |
BASE |