  Falciparum malaria is a major parasitic disease causing widespread morbidity
and mortality globally. Artemisinin derivatives---the most effective and
widely-used antimalarials that have helped reduce the burden of malaria by 60%
in some areas over the past decade---have recently been found to induce growth
retardation of blood-stage Plasmodium falciparum when applied at clinically
relevant concentrations. To date, no model has been designed to quantify the
growth retardation effect and to predict the influence of this property on in
vivo parasite killing. Here we introduce a mechanistic model of parasite growth
from the ring to trophozoite stage of the parasite's life cycle, and by
modelling the level of staining with an RNA-binding dye, we demonstrate that
the model is able to reproduce fluorescence distribution data from in vitro
experiments using the laboratory 3D7 strain. We quantify the dependence of
growth retardation on drug concentration and demonstrate the model's utility as
a platform to propose experimentally-testable mechanisms of growth retardation.
Furthermore we illustrate that a drug-induced delay in growth may significantly
influence in vivo parasite dynamics, demonstrating the importance of
considering growth retardation in the design of optimal artemisinin-based
dosing regimens.
