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Flow cytometry is an objective method for conducting in vitro antimalarial sensitivity assays with increasing potential for application in field sites. We examined in vitro susceptibility to seven anti-malarial drugs for 40 fresh P. falciparum field isolates via a flow cytometry method (FCM), a colorimetric LDH-based ELISA : DELI), and standard microscopic slide analysis of growth. For FCM, 184/280 (66%) assays met analytical acceptance criteria, compared to 166/280 (59%) for DELI. There was good agreement between FCM and microscopy, while DELI tended to produce higher half-maximal inhibition constants (IC50s) than FCM, with an overall bias of 2.2-fold (Bland-Altman comparison). Values for artesunate and dihydroartemisinin were most affected. Paradoxical increases in signal at very high concentrations of mefloquine and related compounds were more marked with the DELI assay, suggesting that off-target effects on LDH production may be responsible. Loss of FCM signal due to reinvasion or slow growth was observed in a small number of samples. These results extend previous work on use of flow cytometry to determine antimalarial susceptibility in terms of the number of samples, range of drugs, and comparison with other methods.

Original publication

DOI

10.1128/JCM.01226-15

Type

Journal article

Journal

J Clin Microbiol

Publication Date

10/2015

Volume

53

Pages

3296 - 3303

Keywords

Antimalarials, Colorimetry, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Inhibitory Concentration 50, L-Lactate Dehydrogenase, Microscopy, Parasitic Sensitivity Tests, Plasmodium falciparum