New Mathematical Models of Antimalarial Drug Action to Improve Drug Dosing Regimens

  • James M. McCawEmail author
  • Pengxing Cao
  • Sophie Zaloumis
  • Julie A. Simpson
Conference paper
Part of the Mathematics for Industry book series (MFI, volume 28)


Plasmodium falciparum malaria remains a major threat to global public health. Artemisinin-based combination therapies—a critical component of current control strategies—are at risk of failure due to the emergence of artemisinin resistance. To extend the life of artemisinin-based therapies, it is crucial that we develop a better understanding of how they act to reduce parasitemia in the host. Recent laboratory-based experiments have demonstrated that parasites respond to the cumulative, rather than instantaneous, drug concentration. This observation directly challenges the standard paradigm of pharmacokinetic–pharmacodynamic (PK–PD) modelling. Here, we introduce a generalisation to the PK–PD model which accounts for cumulative exposure. Parasites accumulate ‘stress’, which translates into an effective killing rate which can vary with both drug concentration and exposure time. Our model indicates how drug-resistant parasites may avoid killing. Through simulation, we explore alternative drug dosing strategies that may overcome drug resistance.


Mathematics for Industry Biological modelling Malaria Antimalarial drugs 



We thank Leann Tilley and her team (Bio21, The University of Melbourne) for access to data. Pengxing Cao and Sophie Zaloumis were supported by National Health and Medical Research Council project and Centre for Research Excellence funding.


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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • James M. McCaw
    • 1
    Email author
  • Pengxing Cao
    • 1
  • Sophie Zaloumis
    • 2
  • Julie A. Simpson
    • 2
  1. 1.School of Mathematics and StatisticsThe University of MelbourneMelbourneAustralia
  2. 2.Melbourne School of Population and Global HealthThe University of MelbourneMelbourneAustralia

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