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Investigating antigenic variation and other parasite–host interactions in Plasmodium falciparum infections in naïve hosts

Published online by Cambridge University Press:  16 April 2004

M. L. GATTON
Affiliation:
Australian Centre for International and Tropical Health & Nutrition, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Qld 4029, Australia
Q. CHENG
Affiliation:
Department of Drug Resistance and Diagnostics, Australian Army Malaria Institute, Gallipoli Barracks, Enoggera, Qld 4051, Australia

Abstract

Mathematical models of the in-host dynamics of malaria infections provide a valuable tool to explore aspects of the host–parasite interaction that are not possible to investigate experimentally. This paper presents predictions of several important parameter values for 2 parasite strains/groups: parasite PfEMP1 switching rates, dynamics of host anti-PfEMP1 antibodies and parameters related to specific and non-specific host immune responses. A stochastic simulation model of the in-host dynamics of Plasmodium falciparum infections in naïve hosts was used to make these predictions. This model incorporates a novel process to simulate antigenic variation by the parasite, and specific and non-specific immune responses by the host. Comparison of model output to a range of published statistics indicated that the model is capable of reproducing the features of clinical P. falciparum infections, including the characteristic recrudescent behaviour. Using the model, we explored the hypothesized switching mechanism of a fast overall rate of antigenic variation early in an infection and found that it is compatible with chronic infections when the var genes are split into 2 groups; fast and slow switching.

Type
Research Article
Copyright
© 2004 Cambridge University Press

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