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Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling

Julie A Simpson, James McCaw, Pengxing Cao, Freya J.I. Fowkes, Sophie Zaloumis, Ric N Price, Saber Dini
doi: https://doi.org/10.1101/331850
Julie A Simpson
University of Melbourne, Australia;
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  • For correspondence: julieas@unimelb.edu.au
James McCaw
University of Melbourne, Australia;
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Pengxing Cao
University of Melbourne, Australia;
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Freya J.I. Fowkes
Burnet Institute, Australia;
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Sophie Zaloumis
University of Melbourne, Australia;
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Ric N Price
Menzies School of Health Research, Australia
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Saber Dini
University of Melbourne, Australia;
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Abstract

The first line treatment for uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), which consists of an artemisinin derivative co-administered 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-PQ-MQ), for use in South-East Asia, where DHA and PQ 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 varying degrees of DHA and PQ resistance. To incorporate interactions between drugs, a novel model is presented for the combined effect of DHA-PQ-MQ, which illustrates how the interactions can influence treatment efficacy. When combined with a standard regimen of DHA and PQ, the administration of three 8.3 mg/kg doses of MQ was sufficient to achieve parasitological efficacy greater than that currently recommended by WHO guidelines.

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Posted May 27, 2018.
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Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling
Julie A Simpson, James McCaw, Pengxing Cao, Freya J.I. Fowkes, Sophie Zaloumis, Ric N Price, Saber Dini
bioRxiv 331850; doi: https://doi.org/10.1101/331850
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Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling
Julie A Simpson, James McCaw, Pengxing Cao, Freya J.I. Fowkes, Sophie Zaloumis, Ric N Price, Saber Dini
bioRxiv 331850; doi: https://doi.org/10.1101/331850

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