Heteroresistance: an occult threat to the treatment success of resistant tuberculosis Acronym "DeepMTB".

Rifampicin-resistant (RR) tuberculosis (TB) is an especially lethal form of TB, with less than 50% of over 0.5 million patients affected each year reaching successful treatment outcomes. Due to difficulties in defining the full drug resistance profile in each individual patient, there is a tremendous risk of losing key classic- (fluoroquinolones) and new drugs (bedaquiline (BDQ)) at a faster pace than novel drugs can be developed. The Mycobacteriology Unit at ITM is uniquely placed due to its key role as central microbiological laboratory for the largest RR-TB trials conducted to date. The two STREAM and two endTB trials, enrolling over 2000 patients, allow to robustly assess the impact of heteroresistance on treatment outcomes. In collaboration with the University of Antwe , we will use innovative, state-of-the-art methods to test the hypothesis that heteroresistance at RR-TB treatment initiation is associated with microbiological failure. We will be the first to apply targeted deep sequencing to clinical samples of RR-TB clinical trial participants and to quantify culture bias in the detection of heteroresistance. In addition, we aim to quantify the effect of treatment interruption on acquisition of resistance to BDQ, which poses a threat to the durability of new RR-TB regimens. The results will provide a leap forward in our knowledge and provide evidence required for defining the most appropriate diagnostic and management strategies for patients afflicted by RR-TB.

Keywords:TUBERCULOSIS

Disciplines:Bacteriology, Infectious diseases, Microbial diagnostics, Respiratory medicine, Tropical medicine

Project type:Collaboration project