Nonlinear Mixed-Effects Modelling of In Vitro Drug Susceptibility and Molecular Correlates of Multidrug Resistant Plasmodium falciparum

JA Simpson; KM Jamsen; TJC Anderson; S Zaloumis; S Nair; C Woodrow; NJ White; F Nosten; RN Price

Journal article

Nonlinear Mixed-Effects Modelling of In Vitro Drug Susceptibility and Molecular Correlates of Multidrug Resistant Plasmodium falciparum

JA Simpson, KM Jamsen, TJC Anderson, S Zaloumis, S Nair, C Woodrow, NJ White, F Nosten, RN Price

Plos One | Published : 2013

DOI: 10.1371/journal.pone.0069505

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Abstract

The analysis of in vitro anti-malarial drug susceptibility testing is vulnerable to the effects of different statistical approaches and selection biases. These confounding factors were assessed with respect to pfmdr1 gene mutation and amplification in 490 clinical isolates. Two statistical approaches for estimating the drug concentration associated with 50% effect (EC50) were compared: the commonly used standard two-stage (STS) method, and nonlinear mixed-effects modelling. The in vitro concentration-effect relationships for, chloroquine, mefloquine, lumefantrine and artesunate, were derived from clinical isolates obtained from patients on the western border of Thailand. All isolates were ge..

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University of Melbourne Researchers

Julie Simpson Author

Sophie Zaloumis Author

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Awarded by Wellcome Trust

Funding Acknowledgements

The work was supported by the National Health and Medical Research Centre of Australia (NHMRC) Project Grant 1025319. SZ was supported under a NHMRC Centre of Research Excellence grant, ID#1035261, to the Victorian Centre for Biostatistics (ViCBiostat). RNP is a Wellcome Trust Senior Research Fellow in Clinical Science (091625). NJW is a Principal Wellcome Trust Fellow. The research carried out at the Shoklo Malaria Research Unit is part of the Wellcome Trust Mahidol University of Oxford Tropical Medicine Research Programme also supported by the Wellcome Trust of Great Britain. The research carried out at TBRI was supported by National Institutes for Health grant (RO1 AI48071) to Tim JC Anderson, and was conducted in facilities constructed with support from Research Facilities Improvement Program Grant (Number C06 RR013556) from the National Center for Research Resources, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.