A comparative analysis of within-host models of malaria infection with immune response

Horn, Shade (2019-04)

Thesis (MSc)--Stellenbosch University, 2019.

Thesis

ENGLISH ABSTRACT: With growing resistance of malaria parasites to different antimalarial treatments, there is an ever present need for new investigative approaches into disease eradication. The symptoms of the disease commonly include fever, nausea and dizziness, and can be attributed to the response of the immune system to disease. This thus emphasizes the imperativeness of the inclusion of the immune response in investigations. Within-host models are used to describe the disease dynamics within the human host during infection. Models commonly describe the change in populations of disease-associated cells within an individual, over time. Model parameters are usually incorporated as mean values from clinical data or estimated from literature. Apart from experimental error, in reality parameters can vary greatly between individuals. Consequently, it is unclear how much trust should be placed in these mathematical models to describe disease dynamics realistically. In this project, local sensitivity, uncertainty, robustness and global sensitivity analysis was performed on within-host malaria infection models that incorporate the immune system’s response. These analyses were used to determine which processes play an important role in the disease dynamics and can therefore possibly be of interest for drug targeting. The results also indicated whether the description of the disease processes can accommodate heterogeneity and uncertainty while still giving reliable and realistic model predictions. Comparison of the model analysis results in this project allowed for identifying which models would be more relevant in describing biologically realistic disease dynamics under the influence of the human immune response, and would be more suited to further studies to identify possible drug targets.

AFRIKAANSE OPSOMMING: Met groeiende weerstandigheid van malaria parasiete teen verskillende anti-malariese behandeling, is daar 'n groeiende behoefte aan ondersoeke na siekte-uitwissing. Die simptome van die siekte sluit gewoonlik koors, naarheid en duiseligheid in, en kan toegeskryf word aan die respons van die immuunsisteem op die siekte. Dit beklemtoon die noodsaak vir die insluiting van die immuunsisteem in hierdie ondersoeke. Binne-gasheer modelle word gebruik om die siekte-dinamiek binne 'n mens tydens infeksie te beskryf. Modelle beskryf gewoonlik die tyd-afhanklike veranderinge in siekte-verwante selpopulasies binne 'n individu. Model parameters word gewoonlik geïnkorporeer as die gemiddelde waardes van kliniese data of geskat vanaf literatuur. Buiten eksperimentele foute, kan parameters in werklikheid dramaties varieer tussen individue. Dit is dus onduidelik hoeveel vertroue geplaas kan word in die vermoëns van hierdie wiskundige modelle om die dinamiek van die siekte realisties te kan beskryf. In hierdie projek word sensitiwiteit-, onsekerheid-, robuustheid- en globale sensitiwiteitsanalise toegepas op binne-gasheer modelle van malaria infeksie waarin die immuunsisteem se respons ingesluit is. Hierdie analises word gebruik om te bepaal watter prosesse belangrik is vir die dinamiek van die siekte en as moontlik teikens vir farmaseutiese intervensie kan dien. Die resultate dui ook aan of beskrywings van die prosesse heterogeniteit en onsekerheid kan akkommodeer en steeds realistiese en betroubare modelvoorspellings kan lewer. Vergelyking van die model analise resultate kan gebruik word vir die identifisering van modelle wat meer relevant is vir die beskrywing van siekte-dinamiek onder die invloed van die menslike immuunsisteem en wat gebruik kan word vir verdere soeke na teikens vir farmaseutiese intervensie.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/105982
This item appears in the following collections: