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Title: Investigating the efficacy of triple artemisinin-based combination therapies for treating plasmodium falciparum malaria patients using mathematical modeling
Authors: Saber Dini
Sophie Zaloumis
Pengxing Cao
Ric N. Price
Freya J.I. Fowkes
Rob W. Van Der Pluijm
James M. McCaw
Julie A. Simpson
Melbourne School of Population and Global Health
University of Melbourne
Royal Children's Hospital, Melbourne
Menzies School of Health Research
Monash University
Mahidol University
Nuffield Department of Clinical Medicine
Burnet Institute
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Nov-2018
Citation: Antimicrobial Agents and Chemotherapy. Vol.62, No.11 (2018)
Abstract: © 2018 Dini et al. The first line treatment for uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), which consists of an artemisinin derivative coadministered with a longer-acting partner drug. However, the spread of Plasmodium falciparum resistant to both artemisinin and its partner drugs poses a major global threat to malaria control activities. Novel strategies are needed to retard and reverse the spread of these resistant parasites. One such strategy is triple artemisinin-based combination therapy (TACT). We developed a mechanistic within-host mathematical model to investigate the efficacy of a TACT (dihydroartemisinin-piperaquine-mefloquine [DHA-PPQ-MQ]) for use in South-East Asia, where DHA and PPQ resistance are now increasingly prevalent. Comprehensive model simulations were used to explore the degree to which the underlying resistance influences the parasitological outcomes. The effect of MQ dosing on the efficacy of TACT was quantified at various degrees of DHA and PPQ resistance. To incorporate interactions between drugs, a novel model is presented for the combined effect of DHA-PPQ-MQ, which illustrates how the interactions can influence treatment efficacy. When combined with a standard regimen of DHA and PPQ, the administration of three 6.7-mg/kg doses of MQ was sufficient to achieve parasitological efficacy greater than that currently recommended by World Health Organization (WHO) guidelines. As a result, three 8.3-mg/kg doses of MQ, the current WHO-recommended dosing regimen for MQ, combined with DHA-PPQ, has the potential to produce high cure rates in regions where resistance to DHA-PPQ has emerged.
ISSN: 10986596
Appears in Collections:Scopus 2018

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