Cross-resistance of the chloroquine-derivative AQ-13 with amodiaquine in Cambodian Plasmodium falciparum isolates
| Autor: | Rithea Leang, Didier Leroy, Melissa Mairet-Khedim, Camille Roesch, Sopheakvatey Ke, Steven P. Maher, Benoit Witkowski, Flore Nardella |
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| Přispěvatelé: | 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), Malaria Molecular Epidemiology, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Center for Tropical and Emerging Global Diseases, University of Georgia [USA], National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Medicines for Malaria Venture (MMV), Université de Genève (UNIGE), Réseau International des Instituts Pasteur (RIIP), This study was supported by Medicine for Malaria Venture. Flore Nardella was supported by a fellowship from the Fondation Pierre Ledoux Jeunesse Internationale and the Pasteur Institute International Network. Melissa Mairet-Khedim was supported by Initiative 5% Grant (MIVS-ACT Grant #15SANIN211)., We would like to thank the patients who agreed to participate in TES studies and the Cambodian Health Centres 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)-Université Paris Cité (UPCité), Center for Tropical and Emerging Global Diseases [Athens, GA, USA], Université de Genève = University of Geneva (UNIGE), Witkowski, Benoit, Malaria Molecular Epidemiology (MMEU) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Drug Resistance chemistry.chemical_compound 0302 clinical medicine Chloroquine Pharmacology (medical) Clinical efficacy Malaria Falciparum Hypoxanthine MESH: Plasmodium falciparum Original Research biology MESH: Malaria Falciparum MESH: Chloroquine 3. Good health Drug Combinations AcademicSubjects/MED00290 Infectious Diseases [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology MESH: Drug Resistance medicine.drug Microbiology (medical) Plasmodium falciparum 030231 tropical medicine 030106 microbiology Amodiaquine Antimalarials 03 medical and health sciences Asian People Piperaquine parasitic diseases medicine Humans AcademicSubjects/MED00740 MESH: Amodiaquine [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology Cross-resistance Pharmacology MESH: Drug Combinations MESH: Humans business.industry biology.organism_classification medicine.disease Virology MESH: Antimalarials chemistry MESH: Asians AcademicSubjects/MED00230 business Malaria |
| Zdroj: | Journal of Antimicrobial Chemotherapy Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2021, 76 (10), pp.2565-2568. ⟨10.1093/jac/dkab219⟩ Journal of Antimicrobial Chemotherapy, 2021, 76 (10), pp.2565-2568. ⟨10.1093/jac/dkab219⟩ |
| ISSN: | 0305-7453 1460-2091 |
| Popis: | Background Expanding resistance to multiple antimalarials, including chloroquine, in South-East Asia (SEA) urges the development of new therapies. AQ-13, a chloroquine derivative, is a new drug candidate for treating malaria caused by Plasmodium falciparum. Objectives Possible cross-resistance between the 4-aminoquinolines amodiaquine, piperaquine and AQ-13 has not been assessed. In vitro parasite growth assays were used to characterize the susceptibility of multidrug-resistant and susceptible P. falciparum patient isolates to AQ-13. Methods A [3H]hypoxanthine uptake assay and a 384-well high content imaging assay were used to assess efficacy of AQ-13 and desethyl-amodiaquine against 38 P. falciparum isolates. Results We observed a strong cross-resistance between the chloroquine derivative amodiaquine and AQ-13 in Cambodian P. falciparum isolates (Pearson correlation coefficient of 0.8621, P Conclusions In light of the poor efficacy of amodiaquine that we described recently in Cambodia, and its cross resistance with AQ-13, there is a significant risk that similar clinical efficacy of AQ-13-based combinations should be anticipated in areas of amodiaquine resistance. |
| Databáze: | OpenAIRE |
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