Mathematical and statistical analysis of the Trypanosoma brucei slender to stumpy transition. 2004

N J Savill, and J R Seed
Department of Zoology, Cambridge University, Downing Street, Cambridge CB2 3EJ, UK. njs@zoo.cam.ac.uk

We propose a new model for the Stumpy Induction Factor-induced slender to stumpy transformation of Trypanosoma brucei gambiense cells in immunosuppressed mice. The model is a set of delay differential equations that describe the time-course of the infection. We fit the model, using a maximum-likelihood method, to previously published data on parasitaemia in four mice. The model is shown to be a good fit and parameter estimates and confidence intervals are derived. Our estimated parameter values are consistent with estimates from previous experimental studies. The model predicts the following. Slender cells can be classified as uncommitted, committed and dividing, and committed and non-dividing. A committed slender cell undergoes about 5 divisions before exiting the cell-cycle. Committed slender cells must produce SIF, and stumpy cells must not produce SIF. There are two mechanisms for differentiation, a background differentiation rate, and a SIF-concentration-dependent differentiation rate, which is proportional to SIF concentration. SIF has a half-life of about 1.4 h in mice. We also show, with suitable changes in the parameter values, that the model reflects behaviours seen in other host species and trypanosome strains.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D009716 Numerical Analysis, Computer-Assisted Computer-assisted study of methods for obtaining useful quantitative solutions to problems that have been expressed mathematically. Analysis, Computer-Assisted Numerical,Computer-Assisted Numerical Analysis,Analyses, Computer-Assisted Numerical,Analysis, Computer Assisted Numerical,Computer Assisted Numerical Analysis,Computer-Assisted Numerical Analyses,Numerical Analyses, Computer-Assisted,Numerical Analysis, Computer Assisted
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014346 Trypanosoma brucei brucei A hemoflagellate subspecies of parasitic protozoa that causes nagana in domestic and game animals in Africa. It apparently does not infect humans. It is transmitted by bites of tsetse flies (Glossina). Trypanosoma brucei,Trypanosoma brucei bruceus,Trypanosoma bruceus,brucei brucei, Trypanosoma,brucei, Trypanosoma brucei,bruceus, Trypanosoma,bruceus, Trypanosoma brucei
D015800 Protozoan Proteins Proteins found in any species of protozoan. Proteins, Protozoan
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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