Clearance of young parasite forms following treatment of falciparum malaria in humans: Comparison of three simple mathematical models

Abstract

To characterize post-treatment clearance of young forms of Plasmodium falciparum from the blood, three differential equation models, a linear decline, a linear then logarithmic decline, and the Michaelis-Menten (MM) kinetic equation, were fitted to log-transformed serial parasite counts from 30 semi-immune patients with synchronous parasitaemias allocated one of six antimalarial drug regimens. The first two equations were solved analytically. The MM equation was solved numerically using a fifth-order Runge-Kutta method. For each equation, parasite clearance was assumed stochastic and log-transformed parasite counts were assumed to be normally distributed at each time-point. Comparisons between models were by Minimum Akaike Information Criterion Estimate. A constrained MM equation fitted the data at least as well as the other two models in 5 of 6 drug groups and also when pooled data were analysed, providing a single index which could be used in drug efficacy studies in similar situations or as part of more complex models that encompass asynchronous, complicated infections.