In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene

Malaria Journal

Research

Nicolas Taudon¹  Daniel Parzy¹  Lionel Bertaux¹  Julien Cren¹  Marilyn Madamet²  Dominique Travers³  Bruno Pradines³  Aurélie Pascual³  Nicolas Benoit⁴  Rémy Amalvict⁴  Christophe Rogier⁵ 

[1] Centre National de Référence du Paludisme, Marseille, France;UMR MD3, Aix Marseille Université, Institut de Recherche Biomédicale des Armées, Marseille, France;Centre National de Référence du Paludisme, Marseille, France;UMR MD3, Aix Marseille Université, Institut de Recherche Biomédicale des Armées, Marseille, France;Equipe Résidente de Recherche en Infectiologie Tropicale, Institut de Recherche Biomédicale des Armées, Hôpital d’Instruction des Armées Laveran, Marseille, France;Département d’Infectiologie de Terrain, Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France;Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, 1095, Inserm, Marseille, France;Centre National de Référence du Paludisme, Marseille, France;Département d’Infectiologie de Terrain, Unité de Parasitologie, Institut de Recherche Biomédicale des Armées, Marseille, France;Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, UM 63, CNRS 7278, IRD 198, 1095, Inserm, Marseille, France;Centre National de Référence du Paludisme, Marseille, France;Equipe Résidente de Recherche en Infectiologie Tropicale, Institut de Recherche Biomédicale des Armées, Hôpital d’Instruction des Armées Laveran, Marseille, France;Institut Pasteur de Madagascar, Antananarivo, Madagascar;

关键词: Malaria;    Plasmodium falciparum;    Anti-malarial;    Resistance;    in vitro;    Molecular marker;    Piperaquine;    Chloroquine;    pfcrt;   

DOI  :  10.1186/1475-2875-12-431

 received in 2013-07-04, accepted in 2013-11-22,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundDihydroartemisinin-piperaquine is a new ACT that is administered as single daily dose for three days and has been demonstrated to be tolerated and highly effective for the treatment of uncomplicated Plasmodium falciparum malaria. Piperaquine was used alone to replace chloroquine as the first-line treatment for uncomplicated malaria in China in response to increasing chloroquine resistance in the 1970s. However, the rapid emergence of piperaquine-resistant strains that resulted in the cessation of its use in China in the 1980s, suggests that there is cross-resistance between piperaquine and chloroquine. Very few data are available on cross-resistance between piperaquine and chloroquine, and the data that do exist are often contradictory.MethodsIn total, 280 P. falciparum isolates, collected between April 2008 and June 2012 from patients hospitalized in France with imported malaria from a malaria-endemic country, were assessed ex vivo for piperaquine and chloroquine susceptibilities by using the standard 42-hour 3H-hypoxanthine uptake inhibition method. The chloroquine resistance-associated mutation K76T in pfcrt was also investigated for the 280 isolates.ResultsThe IC50 for piperaquine ranged from 9.8 nM to 217.3 nM (mean = 81.3 nM. The IC50 for chloroquine ranged from 5.0 nM to 1,918 nM (mean = 83.6 nM. A significant but low correlation was observed between the Log IC50 values for piperaquine and chloroquine (r = 0.145, p < 0.001). However, the coefficient of determination of 0.021 indicates that only 2.1% of the variation in the response to piperaquine is explained by the variation in the response to chloroquine. The mean value for piperaquine was 74.0 nM in the Pfcrt K76 wild-type group (no = 125) and 87.7 nM in the 76 T mutant group (no = 155). This difference was not significant (p = 0.875, Mann Whitney U test).ConclusionsThe present work demonstrates that there was no cross-resistance between piperaquine and chloroquine among 280 P. falciparum isolates and that piperaquine susceptibility is not associated with pfcrt, the gene involved in chloroquine resistance. These results confirm the efficacy of piperaquine in association with dihydroartemisinin and support its use in areas in which parasites are resistant to chloroquine.

【 授权许可】

Unknown   
© Pascual et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.