Plasmodium falciparum Polymorphisms Associated with Ex Vivo Drug Susceptibility and Clinical Effectiveness of Artemisinin-Based Combination Therapies in Benin
| Autor: | Philippe Deloron, Sandrine Houzé, Jean-François Faucher, Abel Wakpo, Sem Ezinmegnon, Eric Kendjo, Pascal Houzé, Oumou Maïga-Ascofaré, Agnès Aubouy, Achille Massougbodji, Jacques Le Bras, Sabina Dahlström |
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| Přispěvatelé: | Institut de médecine et d'épidémiologie appliquée [AP-HP Hôpital Bichat-Claude Bernard] (IMEA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et l’Enfance (CERPAGE), University of Abomey Calavi (UAC), Service de Biochimie [AP-HP Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut d'études romanes - Université de Tübingen, PRES Sorbonne Paris Cité, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et l’Enfance [Cotonou, Bénin] (CERPAGE), Université d’Abomey-Calavi = University of Abomey Calavi (UAC), Institute for Tropical Medicine = Institut für Tropenmedizin, Reisemedizin, Humanparasitolgie [Tübingen, Allemagne] (ITM), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen |
| Rok vydání: | 2014 |
| Předmět: |
Male
deethylamodiaquine ex vivo study [SDV]Life Sciences [q-bio] medicine.medical_treatment Protozoan Proteins Pharmacology growth inhibition dihydroartemisinin chemistry.chemical_compound 0302 clinical medicine genetic linkage Benin Pharmacology (medical) Artemisinin 0303 health sciences Quinine biology Mefloquine pyrimethamine plus sulfadoxine/pd [Pharmacology] amodiaquine plus artesunate/pd [Pharmacology] lactate dehydrogenase/ec [Endogenous Compound] allele article Artemisinins 3. Good health Drug Combinations Pyrimethamine Infectious Diseases priority journal Ethanolamines malaria falciparum/dt [Drug Therapy] Female Multidrug Resistance-Associated Proteins medicine.drug artemether plus benflumetol/pd [Pharmacology] Sulfadoxine Plasmodium falciparum 030231 tropical medicine cloning malaria recurrent infection/dt [Drug Therapy] Dihydroartemisinin artemether plus benflumetol/dt [Drug Therapy] Lumefantrine yttrium 86 Polymorphism Single Nucleotide reinfection Antimalarials Inhibitory Concentration 50 03 medical and health sciences Mechanisms of Resistance parasitic diseases medicine follow up Humans controlled study human drug sensitivity outcome assessment benflumetol Fluorenes lactate dehydrogenase blood level 030306 microbiology clinical effectiveness Amodiaquine Membrane Transport Proteins IC 50 biology.organism_classification major clinical study enzyme linked immunosorbent assay drug efficacy amodiaquine plus artesunate/dt [Drug Therapy] chemistry DNA polymorphism pyrimethamine plus sulfadoxine/dt [Drug Therapy] |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2013, 58 (1), pp.1-10. ⟨10.1128/AAC.01790-12⟩ Antimicrobial Agents and Chemotherapy, 2014, 58 (1), pp.1-10. ⟨10.1128/AAC.01790-12⟩ |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Artemisinin-based combination therapies (ACTs) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. We assessed the association of Plasmodium falciparum polymorphisms and ex vivo drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine ( n = 96), fixed-dose artesunate-amodiaquine ( n = 96), and sulfadoxine-pyrimethamine ( n = 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed. pfcrt , pfmdr1 , pfmrp1 , pfdhfr , and pfdhps polymorphisms were analyzed pretreatment and in recurrent infections. Drug susceptibility was determined in fresh baseline isolates by Plasmodium lactate dehydrogenase enzyme-linked immunosorbent assay (ELISA). A majority had 50% inhibitory concentration (IC 50 ) estimates (the concentration required for 50% growth inhibition) lower than those of the 3D7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine IC 50 s were higher. No association was found between susceptibility to the ACT compounds and treatment outcome. Selection was observed for the pfmdr1 N86 allele in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%] versus 36/195 [18.5%]), and of the opposite allele, 86Y, in artesunate-amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%]) compared to baseline infections. The importance of pfmdr1 N86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine IC 50 s. Genetic linkage between N86 and Y184 was observed, which together with the low frequency of 1246Y may explain regional differences in selection of pfmdr1 loci. Selection of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. Surveillance based on clinical, ex vivo , molecular, and pharmacological data is warranted. |
| Databáze: | OpenAIRE |
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