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Population dynamics of untreated Plasmodium falciparum malaria within the adult human host during the expansion phase of the infection

Published online by Cambridge University Press:  05 August 2002

J. A. SIMPSON ,
L. AARONS ,
W. E. COLLINS ,
G. M. JEFFERY  and
N. J. WHITE
J. A. SIMPSON
Affiliation:
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Department of General Practice and Primary Care, University of Aberdeen, Aberdeen, UK
L. AARONS
Affiliation:
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK
W. E. COLLINS
Affiliation:
Division of Parasitic Diseases, Centers for Disease Control and Prevention, U.S. Public Health Service, Department of Health and Human Services, Atlanta, Georgia, USA
G. M. JEFFERY
Affiliation:
Division of Parasitic Diseases, Centers for Disease Control and Prevention, U.S. Public Health Service, Department of Health and Human Services, Atlanta, Georgia, USA
N. J. WHITE
Affiliation:
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK
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Abstract

A retrospective analysis was performed of parasite count data recorded from the first 7 days of blood or mosquito transmitted Plasmodium falciparum infections given for the treatment of neurosyphilis in the USA before 1963. The objective of this study was to characterize initial growth dynamics before host defences have significant effects on the infecting parasite population. Of the 328 patients' data available for analysis, 83 were excluded because they had received anti-malarial treatment during the first 7 days of the patent infection. Nonlinear mixed effects modelling was performed to estimate the parameters of interest; ‘parasite multiplication rate per 48 h’ (PMR), and length of the parasite life-cycle (periodicity). The parasitaemia versus time profiles showed great variability between patients. The mean population estimate of ‘PMR’ was approximately 8, and was highly dependent on the P. falciparum ‘strain’. PMR also varied significantly between patients with a 90% prediction interval varying from 5·5 to 12·3-fold. Both intrinsic parasite multiplication rate (an intrinsic virulence determinant), and host susceptibility and defence contribute to expansion of the parasite biomass and thus disease severity in falciparum malaria.

Keywords

Plasmodium falciparumparasite multiplication rateperiodicitynonlinear mixed effects modelling
Type
Research Article
Information
Parasitology , Volume 124 , Issue 3 , March 2002 , pp. 247 - 263
Copyright
2002 Cambridge University Press

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