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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
In vitro piperaquine susceptibility is not associated with the Plasmodium falciparum chloroquine resistance transporter gene
Malaria Journal, Volume 12, No. 1, Article 431, Year 2013
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Description
Background: Dihydroartemisinin-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. Methods. In 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. Results: The IC§ssub§50§ esub§ for piperaquine ranged from 9.8 nM to 217.3 nM (mean = 81.3 nM. The IC§ssub§50§esub§ 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 IC§ssub§50§esub§ 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). Conclusions: The 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. © 2013 Pascual et al.; licensee BioMed Central Ltd.
Authors & Co-Authors
Pascual, Aurélie M.
France, Bretigny-sur-orge
Institut de Recherche Biomédicale Des Armées
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
Madamet, Marylin
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Aix Marseille Université
France, Marseille
Hia Laveran a Marseille
Bertaux, Lionel
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Aix Marseille Université
Amalvict, Rémy
France, Bretigny-sur-orge
Institut de Recherche Biomédicale Des Armées
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Hia Laveran a Marseille
Benoit, Nicolas
France, Bretigny-sur-orge
Institut de Recherche Biomédicale Des Armées
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Hia Laveran a Marseille
Travers, Dominique
France, Bretigny-sur-orge
Institut de Recherche Biomédicale Des Armées
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
Cren, Julien
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Aix Marseille Université
Taudon, Nicolas
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Aix Marseille Université
Rogier, Christophe
Madagascar, Antananarivo
Institut Pasteur de Madagascar
Parzy, Daniel
France, Marseille
Centre National de Référence du Paludisme
France, Marseille
Aix Marseille Université
Pradines, Bruno
France, Bretigny-sur-orge
Institut de Recherche Biomédicale Des Armées
France, Marseille
Unité de Recherche Sur Les Maladies Infectieuses et Tropicales Emergentes
France, Marseille
Centre National de Référence du Paludisme
Statistics
Citations: 30
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1186/1475-2875-12-431
e-ISSN:
14752875
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases