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We represent a community with a shared interest in data analysis using the population approach.


2001
   Basel, Switzerland

The natural progression of P.falciparum malaria:- Investigation of a historical cohort of syphilis patients treated with malariatherapy.

Julie A Simpson 1,2,3; Leon Aarons 4; William E Collins 5; Geoffrey M Jeffrey 5; Nicholas J White 1,2;

1. Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. 2. Centre for Tropical Medicine, University of Oxford, Oxford, UK. 3. Department of General Practice and Primary Care, University of Aberdeen, Aberdeen, UK. 4. School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK. 5. Division of Parasitic Diseases, Centres for Disease Control and Prevention, Atlanta, Georgia, U.S.A.

A retrospective analysis was performed of parasite count data recorded from the first seven days of blood or mosquito transmitted P.falciparum infections given for the treatment of neurosyphilis in the USA before 1963. The objective of this was to characterise initial growth dynamics before host defences have significant effects on the infecting parasite population. Of the 328 patients available for analysis, 83 were excluded because they had received antimalarial treatment during the first seven days of the patent infection. Different statistical methods were used to estimate the parameters of interest, 'parasite multiplication rate 48 hours' (PMR) and 'periodicity' of the parasite life cycle. The methods were the Standard two-stage (STS) method, Global two-stage (GTS) method and nonlinear mixed effects modelling.

The parasitaemia versus time profiles showed great variability between patients. The three statistical methods applied to fit the empirical model to the data produced nearly identical parameter estimates, but varying estimates were observed for the inter-patient variability of some of the parameters. The mean population estimate of 'PMR' was approximately 8, and was highly dependent on the P.falciparum strain. PMR also varied significantly between patients. The mean population estimate of the length of the parasite life cycle was approximately 55 hours (2.3 days) which is greater than the generally quoted 48 hours. Intra-host models and pharmacokinetic-pharmacodynamic models that include parasite multiplication must incorporate both variation between parasites and individual hosts.



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