In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays
Abstract Background Pyronaridine, a Mannich base anti-malarial with high efficacy against drug resistant Plasmodium falciparum , is currently evaluated as a fixed dose combination with artesunate for the treatment of uncomplicated malaria. In this study, the in vitro activity of pyronaridine against...
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ftdoajarticles:oai:doaj.org/article:f38cd88ff10144a4abc5b20f069562d2 2023-05-15T15:10:36+02:00 In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays Pongratz Peter Kurth Florian Bélard Sabine Mordmüller Benjamin Kremsner Peter G Ramharter Michael 2009-04-01T00:00:00Z https://doi.org/10.1186/1475-2875-8-79 https://doaj.org/article/f38cd88ff10144a4abc5b20f069562d2 EN eng BMC http://www.malariajournal.com/content/8/1/79 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-79 1475-2875 https://doaj.org/article/f38cd88ff10144a4abc5b20f069562d2 Malaria Journal, Vol 8, Iss 1, p 79 (2009) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2009 ftdoajarticles https://doi.org/10.1186/1475-2875-8-79 2022-12-30T21:52:33Z Abstract Background Pyronaridine, a Mannich base anti-malarial with high efficacy against drug resistant Plasmodium falciparum , is currently evaluated as a fixed dose combination with artesunate for the treatment of uncomplicated malaria. In this study, the in vitro activity of pyronaridine against clinical isolates of P. falciparum from Lambaréné, Gabon, was assessed in order to obtain baseline data on its activity prior to its future use in routine therapy. Moreover, follow-up assessment on the in vitro activity of chloroquine, artesunate and quinine was performed. Methods In vitro response of field isolates of P. falciparum to pyronaridine, chloroquine, artesunate and quinine was assessed using the traditional WHO microtest. In addition, the histidine-rich protein 2 (HRP-2) assay was performed and evaluated for its future implementation for follow-up of drug susceptibility testing. Results Pyronaridine exhibited a high in vitro activity against P. falciparum , with a geometric mean cut-off concentration of 9.3 nmol/l. Fifty percent effective concentrations were 1.9 nmol/l and 2.0 nmol/l in the WHO microtest and HRP-2 assay, respectively. Results matched closely in vivo findings from a recent clinical trial on pyronaridine-artesunate treatment. One isolate showed diminished sensitivity to artesunate. For chloroquine and quinine resistance levels were comparable to prior studies from Lambaréné. Results from the novel HRP-2 assay corresponded well to those obtained by the WHO microtest. Conclusion Pyronaridine is highly active in chloroquine-resistant parasites and seems a promising partner drug for artemisinin-based combination therapy in Africa. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 8 1 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Pongratz Peter Kurth Florian Bélard Sabine Mordmüller Benjamin Kremsner Peter G Ramharter Michael In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Pyronaridine, a Mannich base anti-malarial with high efficacy against drug resistant Plasmodium falciparum , is currently evaluated as a fixed dose combination with artesunate for the treatment of uncomplicated malaria. In this study, the in vitro activity of pyronaridine against clinical isolates of P. falciparum from Lambaréné, Gabon, was assessed in order to obtain baseline data on its activity prior to its future use in routine therapy. Moreover, follow-up assessment on the in vitro activity of chloroquine, artesunate and quinine was performed. Methods In vitro response of field isolates of P. falciparum to pyronaridine, chloroquine, artesunate and quinine was assessed using the traditional WHO microtest. In addition, the histidine-rich protein 2 (HRP-2) assay was performed and evaluated for its future implementation for follow-up of drug susceptibility testing. Results Pyronaridine exhibited a high in vitro activity against P. falciparum , with a geometric mean cut-off concentration of 9.3 nmol/l. Fifty percent effective concentrations were 1.9 nmol/l and 2.0 nmol/l in the WHO microtest and HRP-2 assay, respectively. Results matched closely in vivo findings from a recent clinical trial on pyronaridine-artesunate treatment. One isolate showed diminished sensitivity to artesunate. For chloroquine and quinine resistance levels were comparable to prior studies from Lambaréné. Results from the novel HRP-2 assay corresponded well to those obtained by the WHO microtest. Conclusion Pyronaridine is highly active in chloroquine-resistant parasites and seems a promising partner drug for artemisinin-based combination therapy in Africa. |
format |
Article in Journal/Newspaper |
author |
Pongratz Peter Kurth Florian Bélard Sabine Mordmüller Benjamin Kremsner Peter G Ramharter Michael |
author_facet |
Pongratz Peter Kurth Florian Bélard Sabine Mordmüller Benjamin Kremsner Peter G Ramharter Michael |
author_sort |
Pongratz Peter |
title |
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
title_short |
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
title_full |
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
title_fullStr |
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
title_full_unstemmed |
In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
title_sort |
in vitro activity of pyronaridine against plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays |
publisher |
BMC |
publishDate |
2009 |
url |
https://doi.org/10.1186/1475-2875-8-79 https://doaj.org/article/f38cd88ff10144a4abc5b20f069562d2 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 8, Iss 1, p 79 (2009) |
op_relation |
http://www.malariajournal.com/content/8/1/79 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-8-79 1475-2875 https://doaj.org/article/f38cd88ff10144a4abc5b20f069562d2 |
op_doi |
https://doi.org/10.1186/1475-2875-8-79 |
container_title |
Malaria Journal |
container_volume |
8 |
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1 |
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1766341596661415936 |