Abstract
Even after decades of attempted control, tuberculosis (TB) remains the world's deadliest infectious disease. The resistance of Mycobacterium tuberculosis (MTB) to the most powerful anti-TB drug, rifampicin, poses a primary threat to global TB care, with around 500,000 new patients developing rifampicin-resistant TB (RR-TB) worldwide each year. New approaches are needed to close the detection gap of RR-TB and improve treatment success while preventing acquired resistance to 2nd-line drugs. This project will tackle the main current challenges in the field of RR-TB, from diagnosis of patients until confirmed cure. First, I will study the performance of the Xpert Ultra and its impact on the diagnostic flowchart in Rwanda. Secondly, I will be the first to develop and implement an innovative and accessible direct-on sputum phenotypic drug-susceptibility testing (pDST) assay for the detection of resistance to 2nd-line drugs. Once direct pDST is established, I will evaluate its potential to monitor MTB viability and emerging resistance to fluroquinolones and bedaquiline. Finally, I will evaluate the early bactericidal activity of the 2020-WHO-recommended all-oral treatment regimen versus the previous injectable-based regimen. These findings will inform optimal and simplified rifampicin and 2nd-line drug DST algorithm with the aim to achieve the global target 'universal DST' in Rwanda and elsewhere and help identify critical next steps towards safe and effective RR-TB treatment.
Researcher(s)
Research team(s)
Project type(s)