Charles J. WoodrowSabina DahlströmRichard CookseyJennifer A. FleggHervé Le NagardFrance MentréClaribel MurilloDidier MénardFrançois NostenKanlaya SriprawatLise MussetNeils B. QuashiePharath LimRick M. FairhurstSam L. NsobyaVeronique SinouHarald NoedlBruno PradinesJacob D. JohnsonPhilippe J. GuerinCarol H. SibleyJacques Le BrasNuffield Department of Clinical MedicineMahidol UniversityHopital Bichat-Claude-Bernard AP-HPUniversite Paris 7- Denis DiderotCentro Internacional de Entrenamiento e Investigaciones MedicasInstitut Pasteur du CambodgeShoklo Malaria Research UnitInstitut Pasteur de la GuyaneUniversity of GhanaNational Institute of Allergy and Infectious DiseasesNational Center for Parasitology, Entomology and Malaria ControlMakerere UniversityAix Marseille UniversiteMedizinische Universitat WienInstitut de recherche biomedicale des armeesUnite de Recherche sur les Maladies Infectieuses et Tropicales emergentesCentre National de Référence du PaludismeWalter Reed ProjectUniversity of Washington, SeattleUniversite Paris DescartesIRD Institut de Recherche pour le Developpement2018-10-192018-10-192013-07-01Antimicrobial Agents and Chemotherapy. Vol.57, No.7 (2013), 3121-313010986596006648042-s2.0-84879030186https://repository.li.mahidol.ac.th/handle/20.500.14594/32285Assessment 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.Mahidol UniversityMedicinePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1128/AAC.02350-12