Curbing rifampicin-resistant tuberculosis in Rwanda and beyond

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 (RRTB) 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 2ndline 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.