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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum
Malaria Journal, Volume 11, Article 45, Year 2012
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Description
Background: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN). Methods. The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours 3H-hypoxanthine uptake inhibition method. Results: The IC 50values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC 50and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs. Conclusions: In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs. © 2012 Pascual et al; licensee BioMed Central Ltd.
Authors & Co-Authors
Pascual, Aurélie M.
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
Parola, Philippe
France, Marseille
Hôpital Nord Ap-hm
Benoit-Vical, Françoise
France, Toulouse
Hôpital Rangueil
Simon, Fabrice
France, Marseille
Hia Laveran a Marseille
Malvy, Denis Jean Marie
France, Talence
Centre Hospitalier Universitaire de Bordeaux
Picot, Stèphane
France, Villeurbanne
Institut de Chimie et Biochimie Moléculaire et Supramoléculaire
Delaunay, Pascal
France, Nice
Centre Hospitalier Universitaire de Nice, Hôpital L'archet
Basset, Didier
France, Montpellier
Centre Hospitalier Universitaire de Montpellier
Maubon, Danièle
France, Saint Martin D'heres
Université Grenoble Alpes
Faugére, Bernard
France, Marseille
Hopital la Timone
Ménard, Guillaume
France, Toulon
Hia Sainte-anne a Toulon
Bourgeois, Nathalie
France, Nimes
Hôpital Universitaire Carémeau
Oeuvray, Claude
Switzerland, Geneve
Medicines for Malaria Venture
Rogier, Christophe
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
Pradines, Bruno
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
Statistics
Citations: 23
Authors: 15
Affiliations: 14
Identifiers
Doi:
10.1186/1475-2875-11-45
ISSN:
14752875