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

Published online by Cambridge University Press:  01 August 1997

T. M. E. DAVIS
Affiliation:
University of Western Australia, Department of Medicine, Fremantle Hospital, P.O. Box 480, Fremantle, Western Australia 6160, Australia
R. B. MARTIN
Affiliation:
University of Ottawa, Department of Psychiatry: Affective Disorders, Royal Ottawa Hospital, 1145 Carling, Ottawa, Ontario K1Z 7K4, Canada
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Abstract

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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.

Type
Research Article
Copyright
© 1997 Cambridge University Press