In Silico Investigation of the Decline in Clinical Efficacy of Artemisinin Combination Therapies Due to Increasing Artemisinin and Partner Drug Resistance

Sophie G Zaloumis; Pengxing Cao; Saber Dini; Miles P Davenport; Deborah Cromer; David S Khoury; Freya JI Fowkes; James M McCaw; Julie A Simpson

Journal article

In Silico Investigation of the Decline in Clinical Efficacy of Artemisinin Combination Therapies Due to Increasing Artemisinin and Partner Drug Resistance

Sophie G Zaloumis, Pengxing Cao, Saber Dini, Miles P Davenport, Deborah Cromer, David S Khoury, Freya JI Fowkes, James M McCaw, Julie A Simpson

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | AMER SOC MICROBIOLOGY | Published : 2018

DOI: 10.1128/AAC.01292-18

Abstract

Antimalarial treatment currently relies on an artemisinin derivative and a longer-acting partner drug. With the emergence of resistance to the artemisinin derivatives and the potential pressure this exerts on the partner drugs, the impact of resistance to each drug on efficacy needs to be investigated. An in silico exploration of dihydroartemisinin-piperaquine and mefloquine-artesunate, two artemisinin-based combination therapies that are commonly used in Southeast Asia, was performed. The percentage of treatment failures was simulated from a within-host pharmacokinetic-pharmacodynamic (PKPD) model, assuming that parasites developed increasing levels of (i) artemisinin derivative resistance ..

View full abstract

University of Melbourne Researchers

Pengxing Cao Author Mathematics and Statistics

Freya Fowkes Author Melbourne School of Population and Global Health

James McCaw Author Mathematics and Statistics

Sophie Zaloumis Author Melbourne School of Population and Global Health

Saber Dini Author Melbourne School of Population and Global Health

Related Projects (4)

Mathematical and statistical modelling of antimalarial drug action

This project aims to develop a mathematical model to optimise global antimalarial treatment policy. Malaria-causing parasites are resistant ..

INTEGRATION OF BIOSTATISTICS AND MATHEMATICAL MODELLING TO IMPROVE THE CONTROL OF INFECTIOUS DISEASES

Improving the control of infectious diseases requires the evaluation of interventions that prevent disease at the population level and succe..

SLOWING THE SPREAD OF MALARIA DRUG RESISTANCE BY EXTENDING THE LIFESPAN OF THE ARTEMISININ DERIVATIVES

Approximately 200 million clinical cases of malaria are treated globally each year. Alarmingly, resistance to the most highly effective anti..

CENTRE FOR RESEARCH EXCELLENCE IN MALARIA ELIMINATION

The CRE will work to accelerate progress towards malaria elimination in our region, through Surveillance, to develop better ways to monitor ..

Grants

Awarded by National Health and Medical Research Council (NHMRC) project grant

Awarded by Australian Research Council (ARC) Discovery Project grant

Awarded by NHMRC Centre of Research Excellence for Biostatistics (Victorian Centre for Biostatistics)

Awarded by Australian Centre of Research Excellence on Malaria Elimination

Awarded by NHMRC Senior Research Fellowship

Awarded by ARC DECRA Fellowship

Awarded by ARC Future Fellowship

Funding Acknowledgements

This work was supported by a National Health and Medical Research Council (NHMRC) project grant (grant 1100394), by an Australian Research Council (ARC) Discovery Project grant (grant 170103076), and in part by an NHMRC Centre of Research Excellence for Biostatistics (Victorian Centre for Biostatistics, grant 1035261) and the Australian Centre of Research Excellence on Malaria Elimination (grant 1134989). J.A.S. is funded by a NHMRC Senior Research Fellowship (grant 1104975), S.G.Z. is funded by an ARC DECRA Fellowship (grant 170100785), and F.J.I.F. is funded by an ARC Future Fellowship (grant 130101122).