High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool
Language: 
English
Abstract: 

Assessment of in vitro susceptibility is a fundamental component of antimalarial surveillance studies, but wide variations in the measurement of parasite growth and the calculation of inhibitory constants make comparisons of data from different laboratories difficult. Here we describe a Web-based, high-throughput in vitro analysis and reporting tool (IVART) generating inhibitory constants for large data sets. Fourteen primary data sets examining laboratory-determined susceptibility to artemisinin derivatives and artemisinin combination therapy partner drugs were collated from 11 laboratories. Drug concentrations associated with half-maximal inhibition of growth (IC50s) were determined by a modified sigmoid Emax model-fitting algorithm, allowing standardized analysis of 7,350 concentration-inhibition assays involving 1,592 isolates. Examination of concentration-inhibition data revealed evidence of apparent paradoxical growth at high concentrations of nonartemisinin drugs, supporting amendment of the method for calculating the maximal drug effect in each assay. Criteria for defining more-reliable IC50s based on estimated confidence intervals and growth ratios improved correlation coefficients for the drug pairs mefloquine-quinine and chloroquine-desethylamodiaquine in 9 of 11 and 8 of 8 data sets, respectively. Further analysis showed that maximal drug inhibition was higher for artemisinins than for other drugs, particularly in ELISA (enzyme-linked immunosorbent assay)-based assays, a finding consistent with the earlier onset of action of these drugs in the parasite life cycle. This is the first high-throughput analytical approach to apply consistent constraints and reliability criteria to large, diverse antimalarial susceptibility data sets. The data also illustrate the distinct biological properties of artemisinins and underline the need to apply more sensitive approaches to assessing in vitro susceptibility to these drugs.

Author(s): 
Woodrow, Charles J.
Dahlstrom, Sabina
Cooksey, Richard
Flegg, Jennifer A.
Le Nagard, Hervé
Mentré, France
Murillo, Claribel
Ménard, Didier
Nosten, François
Sriprawat, Kanlaya
Musset, Lise
Quashie, Neils B.
Lim, Pharath
Fairhurst, Rick M.
Nsobya, Sam L.
Sinou, Veronique
Noedl, Harald
Pradines, Bruno
Johnson, Jacob D.
Guerin, Philippe J.
Sibley, Carol H.
Le Bras, Jacques
Item Type: 
Journal Article
Publication Title: 
Antimicrobial Agents and Chemotherapy
Journal Abbreviation: 
Antimicrob. Agents Chemother.
Publication Date: 
7/13/2015
Publication Year: 
2013
Pages: 
3121-3130
Volume: 
57
Issue: 
7
ISSN: 
1098-6596
DOI: 
10.1128/AAC.02350-12
Library Catalog: 
PubMed
Extra: 
PMID: 23612201 PMCID: PMC3697366

Turabian/Chicago Citation

Charles J. Woodrow, Sabina Dahlstrom, Richard Cooksey, Jennifer A. Flegg, Hervé Le Nagard, France Mentré, Claribel Murillo, Didier Ménard, François Nosten, Kanlaya Sriprawat, Lise Musset, Neils B. Quashie, Pharath Lim, Rick M. Fairhurst, Sam L. Nsobya, Veronique Sinou, Harald Noedl, Bruno Pradines, Jacob D. Johnson, Philippe J. Guerin, Carol H. Sibley and Jacques Le Bras. 7/13/2015. "High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool." Antimicrobial Agents and Chemotherapy 57: 7: 3121-3130. 10.1128/AAC.02350-12.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1128/AAC.02350-12 | issn = 1098-6596 | volume = 57 | pages = 3121-3130 | last = Woodrow | first = Charles J. | coauthors = Dahlstrom, Sabina, Cooksey, Richard, Flegg, Jennifer A., Le Nagard, Hervé, Mentré, France, Murillo, Claribel, Ménard, Didier, Nosten, François, Sriprawat, Kanlaya, Musset, Lise, Quashie, Neils B., Lim, Pharath, Fairhurst, Rick M., Nsobya, Sam L., Sinou, Veronique, Noedl, Harald, Pradines, Bruno, Johnson, Jacob D., Guerin, Philippe J., Sibley, Carol H., Le Bras, Jacques | title = High-throughput analysis of antimalarial susceptibility data by the WorldWide Antimalarial Resistance Network (WWARN) in vitro analysis and reporting tool | journal = Antimicrobial Agents and Chemotherapy | date = 7/13/2015 | pmid = | pmc = }} </ref>