All Title Author
Keywords Abstract

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

DOI: 10.1186/1475-2875-8-79

Full-Text   Cite this paper   Add to My Lib


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


comments powered by Disqus

Contact Us


微信:OALib Journal