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The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine
BACKGROUND: The pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (ACTs) recommended for the treatment of uncomplicated P. falciparum malaria. The emergence of P. falciparum resistance to artemisinin has recently developed in Southeast Asia...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746765/ https://www.ncbi.nlm.nih.gov/pubmed/26858119 http://dx.doi.org/10.1186/s13071-016-1358-z |
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author | Madamet, Marylin Briolant, Sébastien Amalvict, Rémy Benoit, Nicolas Bouchiba, Housem Cren, Julien Pradines, Bruno |
author_facet | Madamet, Marylin Briolant, Sébastien Amalvict, Rémy Benoit, Nicolas Bouchiba, Housem Cren, Julien Pradines, Bruno |
author_sort | Madamet, Marylin |
collection | PubMed |
description | BACKGROUND: The pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (ACTs) recommended for the treatment of uncomplicated P. falciparum malaria. The emergence of P. falciparum resistance to artemisinin has recently developed in Southeast Asia. Little data are available on the association between pyronaridine susceptibility and polymorphisms in genes involved in antimalarial drug resistance. The objective of the present study was to investigate the association between ex vivo responses to pyronaridine and the K76T mutation in the pfcrt gene in P. falciparum isolates. METHODS: The assessment of ex vivo susceptibility to pyronaridine was performed on 296 P. falciparum isolates using a standard 42-h 3H-hypoxanthine uptake inhibition method. The K76T mutation was also investigated. RESULTS: The pyronaridine IC(50) (inhibitory concentration 50 %) ranged from 0.55 to 80.0 nM. Ex vivo responses to pyronaridine were significantly associated with the K76T mutation (p-value = 0.020). The reduced susceptibility to pyronaridine, defined as IC(50) > 60 nM, was significantly associated with the K76T mutation (p-value = 0.004). Using a Bayesian mixture modelling approach, the pyronaridine IC(50) were classified into three components: component A (IC(50) median 15.9 nM), component B (IC(50) median 34.2 nM) and component C (IC(50) median 63.3 nM). The K76T mutation was represented in 46.3 % of the isolates in component A, 47.2 % of the isolates in component B and 73.3 % of the isolates in component C (p-value = 0.021). CONCLUSION: These results showed the ex vivo reduced susceptibility to pyronaridine, i.e., IC(50) > 60 nM, associated with the K76T mutation. |
format | Online Article Text |
id | pubmed-4746765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47467652016-02-10 The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine Madamet, Marylin Briolant, Sébastien Amalvict, Rémy Benoit, Nicolas Bouchiba, Housem Cren, Julien Pradines, Bruno Parasit Vectors Short Report BACKGROUND: The pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (ACTs) recommended for the treatment of uncomplicated P. falciparum malaria. The emergence of P. falciparum resistance to artemisinin has recently developed in Southeast Asia. Little data are available on the association between pyronaridine susceptibility and polymorphisms in genes involved in antimalarial drug resistance. The objective of the present study was to investigate the association between ex vivo responses to pyronaridine and the K76T mutation in the pfcrt gene in P. falciparum isolates. METHODS: The assessment of ex vivo susceptibility to pyronaridine was performed on 296 P. falciparum isolates using a standard 42-h 3H-hypoxanthine uptake inhibition method. The K76T mutation was also investigated. RESULTS: The pyronaridine IC(50) (inhibitory concentration 50 %) ranged from 0.55 to 80.0 nM. Ex vivo responses to pyronaridine were significantly associated with the K76T mutation (p-value = 0.020). The reduced susceptibility to pyronaridine, defined as IC(50) > 60 nM, was significantly associated with the K76T mutation (p-value = 0.004). Using a Bayesian mixture modelling approach, the pyronaridine IC(50) were classified into three components: component A (IC(50) median 15.9 nM), component B (IC(50) median 34.2 nM) and component C (IC(50) median 63.3 nM). The K76T mutation was represented in 46.3 % of the isolates in component A, 47.2 % of the isolates in component B and 73.3 % of the isolates in component C (p-value = 0.021). CONCLUSION: These results showed the ex vivo reduced susceptibility to pyronaridine, i.e., IC(50) > 60 nM, associated with the K76T mutation. BioMed Central 2016-02-09 /pmc/articles/PMC4746765/ /pubmed/26858119 http://dx.doi.org/10.1186/s13071-016-1358-z Text en © Madamet et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 | Short Report Madamet, Marylin Briolant, Sébastien Amalvict, Rémy Benoit, Nicolas Bouchiba, Housem Cren, Julien Pradines, Bruno The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine |
title | The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine |
title_full | The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine |
title_fullStr | The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine |
title_full_unstemmed | The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine |
title_short | The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine |
title_sort | plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo p. falciparum african parasite response to pyronaridine |
topic | Short Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746765/ https://www.ncbi.nlm.nih.gov/pubmed/26858119 http://dx.doi.org/10.1186/s13071-016-1358-z |
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