Linking human genotype and immunological phenotype to understand pathogenesis and improve treatment in tuberculosis

Tuberculosis (TB) kills more people worldwide than any other infectious disease, but if we are to reduce this burden we need to better understand how the disease develops. TB is a complicated disease with many different clinical forms and variations in human genes which affect how the body responds to infection and how a person responds to treatment.

My aim is to better understand the links between human genes and the type and severity of disease. I will investigate TB affecting the lung and brain in adults in Vietnam by analysing the genetic messaging (RNA) expressed by the body to make proteins. This will allow me to compare the body’s response in different forms of TB, particularly inflammation, and assess how different treatments are working. I will investigate: the impact of the anti-inflammatory drug dexamethasone on TB-associated inflammation; the body’s ability to kill bacteria and survival or death from TB in the brain; and how the gene LTA4H affects inflammation. I will also identify other genes that alter inflammation and outcome from TB in the brain and investigate how genes and inflammation are associated with treatment failure or relapse in TB in the lung.

My results will help improve understanding of the links between human genes and the type and severity of TB and this will help improve treatments.

This grant was awarded under the scheme's previous name of Intermediate Fellowships in Public Health and Tropical Medicine.