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Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine
BACKGROUND: In 2002, the World Health Organization recommended that artemisinin-based combination therapy (ACT) be used to treat uncomplicated malaria. Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new combinations. The aim of the present work was to assess the distribu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323025/ https://www.ncbi.nlm.nih.gov/pubmed/25848972 http://dx.doi.org/10.1186/s12936-015-0586-6 |
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author | Pascual, Aurélie Madamet, Marilyn Briolant, Sébastien Gaillard, Tiphaine Amalvict, Rémy Benoit, Nicolas Travers, Dominique Pradines, Bruno |
author_facet | Pascual, Aurélie Madamet, Marilyn Briolant, Sébastien Gaillard, Tiphaine Amalvict, Rémy Benoit, Nicolas Travers, Dominique Pradines, Bruno |
author_sort | Pascual, Aurélie |
collection | PubMed |
description | BACKGROUND: In 2002, the World Health Organization recommended that artemisinin-based combination therapy (ACT) be used to treat uncomplicated malaria. Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new combinations. The aim of the present work was to assess the distribution of the in vitro values of pyronaridine (PND) and piperaquine (PPQ) and to define a cut-off for reduced susceptibility for the two anti-malarial drugs. METHODS: The distribution and range of the 50% inhibitory concentration values (IC(50)) of PND and PPQ were determined for 313 isolates obtained between 2008 and 2012 from patients hospitalized in France for imported malaria. The statistical Bayesian analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to PND and PPQ. RESULTS: The PND IC(50) values ranged from 0.6 to 84.6 nM, with a geometric mean of 21.1 ± 16.0 nM (standard deviation). These values were classified into three components. The PPQ IC(50) values ranged from 9.8 to 217.3 nM, and the geometric mean was 58.0 ± 34.5 nM. All 313 PPQ values were classified into four components. Isolates with IC(50) values greater than 60 nM or four-fold greater than 3D7 IC(50) are considered isolates that have reduced susceptibility to PND and those with IC(50) values greater than 135 nM or 2.3-fold greater than 3D7 IC(50) are considered isolates that have reduced susceptibility to PPQ. CONCLUSION: The existence of at least three phenotypes for PND and four phenotypes for PPQ was demonstrated. Based on the cut-off values, 18 isolates (5.8%) and 13 isolates (4.2%) demonstrated reduced susceptibility to PND and PPQ, respectively. |
format | Online Article Text |
id | pubmed-4323025 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43230252015-02-11 Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine Pascual, Aurélie Madamet, Marilyn Briolant, Sébastien Gaillard, Tiphaine Amalvict, Rémy Benoit, Nicolas Travers, Dominique Pradines, Bruno Malar J Research BACKGROUND: In 2002, the World Health Organization recommended that artemisinin-based combination therapy (ACT) be used to treat uncomplicated malaria. Dihydroartemisinin-piperaquine and artesunate-pyronaridine are two of these new combinations. The aim of the present work was to assess the distribution of the in vitro values of pyronaridine (PND) and piperaquine (PPQ) and to define a cut-off for reduced susceptibility for the two anti-malarial drugs. METHODS: The distribution and range of the 50% inhibitory concentration values (IC(50)) of PND and PPQ were determined for 313 isolates obtained between 2008 and 2012 from patients hospitalized in France for imported malaria. The statistical Bayesian analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to PND and PPQ. RESULTS: The PND IC(50) values ranged from 0.6 to 84.6 nM, with a geometric mean of 21.1 ± 16.0 nM (standard deviation). These values were classified into three components. The PPQ IC(50) values ranged from 9.8 to 217.3 nM, and the geometric mean was 58.0 ± 34.5 nM. All 313 PPQ values were classified into four components. Isolates with IC(50) values greater than 60 nM or four-fold greater than 3D7 IC(50) are considered isolates that have reduced susceptibility to PND and those with IC(50) values greater than 135 nM or 2.3-fold greater than 3D7 IC(50) are considered isolates that have reduced susceptibility to PPQ. CONCLUSION: The existence of at least three phenotypes for PND and four phenotypes for PPQ was demonstrated. Based on the cut-off values, 18 isolates (5.8%) and 13 isolates (4.2%) demonstrated reduced susceptibility to PND and PPQ, respectively. BioMed Central 2015-02-05 /pmc/articles/PMC4323025/ /pubmed/25848972 http://dx.doi.org/10.1186/s12936-015-0586-6 Text en © Pascual et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Pascual, Aurélie Madamet, Marilyn Briolant, Sébastien Gaillard, Tiphaine Amalvict, Rémy Benoit, Nicolas Travers, Dominique Pradines, Bruno Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine |
title | Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine |
title_full | Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine |
title_fullStr | Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine |
title_full_unstemmed | Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine |
title_short | Multinormal in vitro distribution of Plasmodium falciparum susceptibility to piperaquine and pyronaridine |
title_sort | multinormal in vitro distribution of plasmodium falciparum susceptibility to piperaquine and pyronaridine |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323025/ https://www.ncbi.nlm.nih.gov/pubmed/25848972 http://dx.doi.org/10.1186/s12936-015-0586-6 |
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