Improving the evaluation of severe malaria

Severe malaria remains a major cause of preventable childhood mortality in sub-Saharan Africa. Improved understanding of human genetic susceptibility to severe disease and the effect of therapeutic interventions will save lives. A major difficulty for all quantitative research in severe malaria is the evaluation and classification of the severe malaria phenotypes in areas of high transmission. The diagnosis of severe malaria in young children and the distinction from bacterial sepsis is imprecise. The biomarker model will be validated using Mendelian randomisation (natural experiment using genetic polymorphisms with known protective effects). The biomarker model will be then applied to evaluate the effect of blood transfusion in severe malaria and re-evaluate the role of glucose-6-phosphate dehydrogenase deficiency in the protection against severe illness. Underpinning all of the work will be the development of new statistical methods for case-control studies which have phenotypic imprecision in the case definitions. These methods will improve genome-wide association studies in severe malaria and help guide the design of early phase evaluations of new therapeutic interventions.

Diagnostics

Jan 2022 — Dec 2026

$954,872

United Kingdom