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Open Access Research

In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays

Florian Kurth123*, Peter Pongratz12, Sabine Bélard124, Benjamin Mordmüller12, Peter G Kremsner12 and Michael Ramharter15

Author Affiliations

1 Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon

2 Institute for Tropical Medicine, Department of Parasitology, University of Tübingen, Tübingen, Germany

3 Department of Paediatrics, University Hospital Carl Gustav Carus Dresden, Dresden, Germany

4 Department of Pediatrics and Adolescent Medicine, University Freiburg, Freiburg, Germany

5 Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria

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Malaria Journal 2009, 8:79  doi:10.1186/1475-2875-8-79

Published: 23 April 2009

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.