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Within-host Deterministic Modelling of Artesunate Resistance in Plasmodium falciparum
Marselinus Ulu F, 2015
The University of Melbourne
Abstract
A deterministic within-host pharmacokinetic-pharmacodynamic (PK–PD) model in the form of ordinary
differential equations (ODEs) has been generated to understand the artesunate resistance in Plasmodium
falciparum. Using mixed infection assumption, where a single host is infected with artesunate-sensitive
strains and artesunate-resistance strains at time t, we are able to understand the basic characteristics
of some available anti-malarial drugs and the mechanism of the standard three-day artemisinin-based
combination therapy (ACT) treatment protocol recommended by World Health Organisation (WHO) for
uncomplicated falciparum malaria treatment. More importantly, this simpler model is able to describe
how the three-day ACT treatment protocol is fail for treating a single patient with mixed parasite strains
in the bloodstream. It also enables us to propose other alternative treatment strategies to treat a patient
who is infected with resistant strains. It suggests that giving artesunate twice a day in the three-day
(ACT) treatment and administering the fourth dose of artesunate are the best treatment strategies that
can be applied to clear the artesunate-resistant strains.
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