Statistical Evaluation of Two-compartment Mathematical Models for Prediction of Parasite Clearance in Cerebral Malaria

• Activity Number: 266
• Type: Contributed
• Date/Time: Tuesday, August 9, 2005 : 10:30 AM to 12:20 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Wayne Chen*+ and Christine McLaren and Wen-Pin Chen and Sornchai Looareesuwan and Gary M. Brittenham
• Companies: Minnesota State University Moorhead and University of California, Irvine and Chao Family Comprehensive Cancer Center and Mahidol University and Columbia University
• Keywords: malaria ; cerebral malaria ; sequestered malarial parasites ; parasite population dynamics ; curve fitting ; 2-compartment mathematical model

Abstract

Cerebral malaria is one of the most severe manifestations of infection with parasites, Plasmodium falciparum. Accurate clinical evaluation of malarial infection and parasite clearance in response to therapy requires consideration of the natural life cycle of P. falciparum, including both circulation of parasites in the peripheral blood and sequestration in the lining of blood vessels. There is no direct measure of the sequestered parasite population. We evaluated a two-compartment model of parasite population dynamics by Gravenor et al. (1998) for prediction of parasite clearance in children treated for malaria in Bangkok, Thailand. Objectives were to determine the minimum number of sequential blood samples needed and to estimate the population size of the sequestered malarial parasites during therapy. Results show that with only four longitudinal data points, patient-specific model parameter estimates predict the initial sequestered parasite population and discriminate between three types of malaria (uncomplicated, severe, and cerebral). The modeling technique is promising for evaluation of the effect of antimalarial drug therapy.