Nya metoder för diagnostik av aktiv och latent tuberkulos

Bakgrund:

A quarter of the world´s population is infected with Mycobacterium tuberculosis (Mtb) and 10% of those latently infected will develop active tuberculosis (TB) with an increased risk in immunesuppression. Eight million new cases of TB and 1.4 million deaths occur each year. New tools to combat TB are urgently needed.

Our group has developed an assay for diagnosis of TB by the detection of lipoarabinomannan (LAM), a cell wall component of tubercle bacilli that is excreted in urine of infected patients. To provide a simple point of patient care (POC) test we have now developed an even simpler device.

To identify mycobacterial antigens and host markers for immunological diagnosis of individuals with latent TB at risk of developing active disease, we are using single cell mass cytometry followed by cluster analysis, as well as protein profiling to dissect relevant cell subsets and responses of the immune system in patients with active and latent TB. We found that certain monocyte and NK cell subsets display a memory response/trained immunity after stimulation with LAM and its precursor PIM in individuals with latent TB, indicating potential biomarkers for latent TB.

Målsättning:

To determine how the mycobacterial glycolipids LAM and PIM can be used for the identification and follow up of patients with active and various forms of latent TB. Our aims are:

1) To determine the performance of a new prototype of our urinary LAM test for: i) the diagnosis of active TB; and ii) to identify patients with LTB at high risk of developing active TB.

2) To define new diagnostic biomarkers based on LAM and PIM to detect patients with latent TB and identify those who will progress to active TB. Arbetsplan: Following our previous work on the role of LAM and PIM we will:

1) Evaluate a new prototype of our urine based test for active TB diagnosis in clinical settings in TB low- and high-endemic settings. 2) Dissect the pattern of the immune responses elicited by LAM and PIM in patients at different stages of latent TB. Betydelse:

By correct identification and treatment of patients with active and latent TB respectively, and identifying patients with latent TB who are at risk of developing active TB, chains of transmission can be interrupted and the number of secondary cases of active TB reduced. The suffering and costs caused by TB both on an individual basis and for health care as a whole will thus be greatly reduced.