High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool
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, h...
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th-mahidol.322852018-10-19T12:43:44Z High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool Charles J. Woodrow Sabina Dahlström 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 Jacques Le Bras Nuffield Department of Clinical Medicine Mahidol University Hopital Bichat-Claude-Bernard AP-HP Universite Paris 7- Denis Diderot Centro Internacional de Entrenamiento e Investigaciones Medicas Institut Pasteur du Cambodge Shoklo Malaria Research Unit Institut Pasteur de la Guyane University of Ghana National Institute of Allergy and Infectious Diseases National Center for Parasitology, Entomology and Malaria Control Makerere University Aix Marseille Universite Medizinische Universitat Wien Institut de recherche biomedicale des armees Unite de Recherche sur les Maladies Infectieuses et Tropicales emergentes Centre National de Référence du Paludisme Walter Reed Project University of Washington, Seattle Universite Paris Descartes IRD Institut de Recherche pour le Developpement Medicine Pharmacology, Toxicology and Pharmaceutics 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 Emaxmodel-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. Copyright © 2013, American Society for Microbiology. 2018-10-19T05:22:20Z 2018-10-19T05:22:20Z 2013-07-01 Article Antimicrobial Agents and Chemotherapy. Vol.57, No.7 (2013), 3121-3130 10.1128/AAC.02350-12 10986596 00664804 2-s2.0-84879030186 https://repository.li.mahidol.ac.th/handle/123456789/32285 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84879030186&origin=inward |
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Medicine Pharmacology, Toxicology and Pharmaceutics Charles J. Woodrow Sabina Dahlström 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 Jacques Le Bras High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool |
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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 Emaxmodel-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. Copyright © 2013, American Society for Microbiology. |
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Nuffield Department of Clinical Medicine |
author_facet |
Nuffield Department of Clinical Medicine Charles J. Woodrow Sabina Dahlström 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 Jacques Le Bras |
format |
Article |
author |
Charles J. Woodrow Sabina Dahlström 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 Jacques Le Bras |
author_sort |
Charles J. Woodrow |
title |
High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool |
title_short |
High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool |
title_full |
High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool |
title_fullStr |
High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool |
title_full_unstemmed |
High-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (WWARN) In Vitro analysis and reporting tool |
title_sort |
high-throughput analysis of antimalarial susceptibility data by the worldwide antimalarial resistance network (wwarn) in vitro analysis and reporting tool |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/32285 |
_version_ |
1763496455948992512 |