Evaluation of novel immunodiagnostic tests in the diagnosis of tuberculosis

Even though tuberculosis (TB) is currently the world’s most lethal infectious disease, it has been forgotten in the developed world. Estimates suggest that globally 10 million people have developed TB disease in 2017, killing 1.6 million of whom approximately 233’000 were children. With a recent increase in human migration, conflict and climate change, authorities worldwide are faced with growing challenges in providing health. However, diagnostic tools, especially suitable for children and immunocompromised individuals, to ensure proper case detection, are lacking. New tools are urgently needed in order to control the global pandemic.

This PhD thesis aims to look at possibilities to improve immunodiagnosis of TB in children and immunocompromised individuals. Currently used immunodiagnostic tests are insufficient to diagnose TB in these patients groups. Therefore we aimed at assessing risk factors for indeterminate results in IGRA in children. Furthermore a study in children and a study in HIV-positive individuals evaluated the potential of novel Mycobacterium tuberculosis antigens and additional cytokine read-outs in immune-based tests to diagnose TB.

First a systematic review on novel Mycobacterium tuberculosis antigens and their use in immunodiagnosis of TB was performed. Findings of published studies investigating antigens that are not used in commercially available immunodiagnostic tests were summarized and compared. In another systematic review and meta-analysis on indeterminate results of IGRA in children we assessed risk factors contributing to inconclusive results of T-SPOT.TB and QFT in children. Finally a selection of novel Mycobacterium tuberculosis antigens was tested in two different study settings in Switzerland. Immune responses induced by 10 novel antigens were evaluated in children with TB disease, TB infection and healthy, exposed ones. The same antigens were also evaluated in HIV-positive individuals.