Theoretical Development of a Multiscale Computational Model of Malaria Infection Dynamics for Biomedical Device Design Guidance

The design of biomedical devices for malaria diagnosis, treatment monitoring, and drug delivery requires quantitative understanding of Plasmodium falciparum infection dynamics across intracellular, cellular, and systemic physiological scales, but existing computational models of malaria infection do not adequately integrate these scales nor incorporate the specific parasite biology and patient physiology relevant to Nigerian endemic transmission conditions. This dissertation develops an original multiscale computational model of malaria infection dynamics intended to provide quantitative design guidance for malaria biomedical devices in Nigerian transmission settings. The model integrates three coupled sub-models. The intracellular scale sub-model describes Plasmodium falciparum metabolic flux and haemoglobin digestion kinetics during erythrocytic development using a constraint-based metabolic network formulation calibrated to published proteomics data from Nigerian clinical isolates. The cellular scale sub-model describes erythrocyte invasion, rupture, and cytoadherence dynamics using a discrete-event stochastic simulation framework incorporating observed parasite phenotypic distributions from Kano and Lagos clinical isolate datasets. The systemic scale sub-model describes haematological, immunological, and clinical dynamics using coupled ordinary differential equations validated against longitudinal clinical data from the Nigerian malarial anaemia cohort. Cross-scale coupling mechanisms are formulated theoretically and numerically verified. The integrated model is applied to three device design questions: optimal antigen concentration detection sensitivity requirements for next-generation rapid diagnostic tests, pharmacokinetic sampling window specification for therapeutic drug monitoring devices, and erythrocyte biomechanical property change profiles relevant to microfluidic parasite enrichment device design. Original theoretical contributions include the cross-scale coupling formulation and the clinical isolate-derived parasite population heterogeneity models. Keywords: malaria infection model, multiscale computation, biomedical device design, Plasmodium falciparum, Nigeria.