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We describe an age-structured mathematical model of the malaria parasite life cycle that uses clinical observations of peripheral parasitaemia to estimate population dynamics of sequestered parasites, which are hidden from the clinical investigator. First, the model was tested on parasite populations cultured in vitro, and was found to account for approximately 72% of the variation in that sub-population of parasites that would have been sequestered in vivo. Next, the model was applied to patients undergoing antimalarial therapy. Using individual data sets we found that although the model fitted the peripheral parasite curves very well, unique solutions for the fit could not be obtained; therefore, robust estimates of sequestered parasite dynamics remained unavailable. We conclude that even given detailed data on individual parasitaemia, estimates of sequestered numbers may be difficult to obtain. However, if data on individuals undergoing similar therapy are collected at equal time intervals, some of these problems may be overcome by estimating specific parameters over groups of patients. In this manner we estimated sequestered parasite density in a group of patients sampled at identical time points following antimalarial treatment. Using this approach we found significant relationships between changes in parasite density, age structure and temperature that were not apparent from the analysis of peripheral parasitaemia only.

Original publication

DOI

10.1006/jtbi.2002.3030

Type

Journal article

Journal

Journal of theoretical biology

Publication Date

07/2002

Volume

217

Pages

137 - 148

Addresses

Department of Paediatrics, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, U.K. michael.gravenor@bbsrc.ac.uk

Keywords

Erythrocytes, Animals, Humans, Plasmodium falciparum, Parasitemia, Malaria, Falciparum, Population Density, Life Cycle Stages, Models, Biological