Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nature Medicine Année : 2020

Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda

Aline Uwimana
  • Fonction : Auteur correspondant
  • PersonId : 1075449

Connectez-vous pour contacter l'auteur
Frederic Ariey
  • Fonction : Auteur
Monique Murindahabi
  • Fonction : Auteur

Résumé

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.

Domaines

Parasitologie
Fichier principal
Vignette du fichier
s41591-020-1005-2.pdf (3.06 Mo) Télécharger le fichier
Loading...

Dates et versions

pasteur-02911712 , version 1 (04-08-2020)

Licence

Paternité

Identifiants

Citer

Aline Uwimana, Eric Legrand, Barbara Stokes, Jean-Louis Mangala Ndikumana, Marian Warsame, et al.. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nature Medicine, 2020, ⟨10.1038/s41591-020-1005-2⟩. ⟨pasteur-02911712v1⟩
148 Consultations
144 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More