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

DOI: 10.1186/1475-2875-8-79

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Abstract:

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.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.Pyronaridine is highly active in chloroquine-resistant parasites and seems a promising partner drug for artemisinin-based combination therapy in Africa.Malaria continues to be a major cause of morbidity and mortality in sub-Saharan Africa, particularly in young children. Early detection and effective chemotherapy remain the cornerstones in its control [1]. The rapid development and spread of anti-malarial drug resistance has made surveillance of drug sensitivity a high priority issue. In addition to assessing the activity of common anti-malarials against Plasmodium falciparum in routine surveys, the evaluation of new compounds against field isolates is of major importance for drug development.In Lambaréné, Gabon, routine anti-malarial drug susceptibility monitoring has been performed since 1992 [2-5]. So far the WHO microtest – one of the longest used and best validated assays for the assessment of in vitro drug sensitivity under field conditions – has been used for this purpose [6]. Meanwhile, novel methods in drug susceptibility testing have been developed, such

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