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

[摘要] 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.

[发布机构] Stellenbosch University