In vitro activity of ferroquine against artemisinin-based combination therapy (ACT)-resistant Plasmodium falciparum isolates from Cambodia

Autor: Jean Christophe Barale, Chanra Khean, Nimol Khim, Sopheakvatey Ke, Saorin Kim, Benoit Witkowski, Nimol Kloeung, Didier Leboulleux, Pascal Ringwald, Didier Leroy, Didier Menard, Chhayleang Kauy, Rithea Leang, Rotha Eam, Flore Nardella, Alain Pellet, Melissa Mairet-Khedim
Přispěvatelé: Malaria Molecular Epidemiology, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Evotec, National Center of Parasitology (CNM), National Malaria Center [Phnom Penh], National Center for Malariology, Ministry of Health [Phnom Penh], World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Malaria : parasites et hôtes - Malaria : parasites and hosts, Institut Pasteur [Paris], Medicines for Malaria Venture (MMV), Université de Genève (UNIGE), This study was supported by Medicines for Malaria Venture (project RD/13/0002). M. M.-K. and B. W. were supported by 5% initiative [molecular and in vitro surveillance of ACT partner drug efficacy in the Greater Mekong Subregion (MIVS-ACT), grant #15SANIN211]. F. N. was supported by Foundation Pierre Ledoux., We would like to thank the patients who participated in TESs and the Cambodian Health Centre medical staff for their contribution, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université de Genève = University of Geneva (UNIGE), Barale, Jean-Christophe, Malaria Molecular Epidemiology (MMEU)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Journal of Antimicrobial Chemotherapy
Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2019, 74 (11), pp.3240-3244. ⟨10.1093/jac/dkz340⟩
Journal of Antimicrobial Chemotherapy, 2019, 74 (11), pp.3240-3244. ⟨10.1093/jac/dkz340⟩
ISSN: 0305-7453
1460-2091
DOI: 10.1093/jac/dkz340⟩
Popis: Background Cambodia is the epicentre of resistance emergence for virtually all antimalarial drugs. Selection and spread of parasites resistant to artemisinin-based combination therapy (ACT) is a major threat for malaria elimination, hence the need to renew the pool of effective treatments. Objectives To determine whether ACT resistance haplotypes could have an effect on ferroquine in vitro antimalarial activity. Methods In vitro susceptibility to ferroquine was measured for 80 isolates from Cambodia characterized for their molecular resistance profile to artemisinin, piperaquine and mefloquine. Results Among the 80 isolates tested, the overall median (IQR) IC50 of ferroquine was 10.9 nM (8.7–18.3). The ferroquine median (IQR) IC50 was 8.9 nM (8.1–11.8) for Pfk13 WT parasites and was 12.9 nM (9.5–20.0) for Pfk13 C580Y parasites with no amplification of Pfpm2 and Pfmdr1 genes. The median (IQR) IC50 of ferroquine for Pfk13 C580Y parasites with amplification of the Pfpm2 gene was 17.2 nM (14.5–20.5) versus 9.1 nM (7.9–10.7) for Pfk13 C580Y parasites with amplification of the Pfmdr1 gene. Conclusions Ferroquine exerts promising efficacy against ACT-resistant isolates. Whereas Pfpm2 amplification was associated with the highest parasite tolerance to ferroquine, the susceptibility range observed was in accordance with those measured in ACT resistance-free areas. This enables consideration of ferroquine as a relevant therapeutic option against ACT-resistant malaria.
Databáze: OpenAIRE
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