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Journal articles
In vitro activity of ferroquine against artemisinin-based combination therapy (ACT)-resistant Plasmodium falciparum isolates from Cambodia
Mélissa Mairet-Khedim
1
Flore Nardella
2
Nimol Khim
1
Saorin Kim
1
Nimol Kloeung
1
Sopheakvatey Ke
1
Chhayleang Kauy
1
Rotha Eam
1
Chanra Khean
1
Alain Pellet
3
Didier Leboulleux
3
Rithea Leang
4, 5
Pascal Ringwald
6
Jean Christophe Barale
7, 8
Didier Leroy
9
Didier Ménard
2
Benoît Witkowski
1, *
*
Corresponding author
3
Evotec
Pascal Ringwald 6
Author
Jean Christophe Barale 7, 8
Author
Didier Leroy 9
Author
Didier Ménard 2
Author IdHAL : didier-menard ORCID : https://orcid.org/0000-0003-1357-4495
Benoît Witkowski 1
Correspondent author
1
Malaria Molecular Epidemiology (Phnom Penh - Cambodia)
- Institut Pasteur du Cambodge (BP 983 - 5 , Boulevard Monivong, Phnom Penh - Cambodia)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
2
Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions (Département des Parasites et Insectes vecteurs, 25-28, rue du docteur Roux, 75724 Paris Cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1201 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : ERL9195 (France)
3
Evotec
4
CNM - National Center of Parasitology (National Center for Parasitology, Entomology and Malaria Control #372 Monivong Blvd (Corner St.322) - Cambodia)
- National Malaria Center [Phnom Penh] (372 boulevard Monivong, Phnom Penh - Cambodia)
5
National Center for Malariology (Cambodia)
- Ministry of Health [Phnom Penh] (No 151-153 Kampuchea Krom Blvd. Phnom Penh - Cambodia)
6
WHO - World Health Organisation (genève - Switzerland)
- OMS / WHO - Organisation Mondiale de la Santé / World Health Organization Office (Genève - Switzerland)
7
Microb. Struc. (UMR_3528 / U-Pasteur_5) - Microbiologie structurale - Structural Microbiology (Département de Biologie structurale et Chimie, 25-28 rue du Dr Roux 75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] : U-Pasteur_5 (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
- UPD7 - Université Paris Diderot - Paris 7 : UMR_3528 (5 rue Thomas-Mann - 75205 Paris cedex 13 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR_3528 (France)
8
Malaria : parasites et hôtes - Malaria : parasites and hosts (Département Parasites et Insectes Vecteurs
25-28, rue du Docteur Roux
75724 Paris cedex 15 - France)
- Institut Pasteur [Paris] (25-28, rue du docteur Roux, 75724 Paris cedex 15 - France)
9
MMV - Medicines for Malaria Venture (PO Box 1826, ICC Building, 20, rte de Pré-Bois, 1215 Geneva 15, Switzerland - Switzerland)
- UNIGE - Université de Genève (24 rue du Général-Dufour CH - 1211 Genève 4 - Switzerland)
Abstract : 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.
Document type :
Journal articles
Complete list of metadatas
https://hal-pasteur.archives-ouvertes.fr/pasteur-02385376
Contributor : Jean-Christophe Barale <>
Submitted on : Thursday, November 28, 2019 - 5:32:42 PM
Last modification on : Tuesday, May 5, 2020 - 12:10:17 PM
Contributor : Jean-Christophe Barale <>
Submitted on : Thursday, November 28, 2019 - 5:32:42 PM
Last modification on : Tuesday, May 5, 2020 - 12:10:17 PM
Identifiers
- HAL Id : pasteur-02385376, version 1
- DOI : 10.1093/jac/dkz340
- PUBMED : 31518407
Collections
PASTEUR | RIIP | RIIP_CAMBODGE | UNIV-PARIS7 | CNRS | USPC | UNIV-PARIS | UP-SCIENCES
Citation
Mélissa Mairet-Khedim, Flore Nardella, Nimol Khim, Saorin Kim, Nimol Kloeung, et al.. In vitro activity of ferroquine against artemisinin-based combination therapy (ACT)-resistant Plasmodium falciparum isolates from Cambodia. Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2019, 74 (11), pp.3240-3244. ⟨10.1093/jac/dkz340⟩. ⟨pasteur-02385376⟩
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