Curbing rifampicin-resistant tuberculosis in Rwanda and beyond.
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)
- Promoter: Rigouts Leen
- Fellow: Cuella Martin Isabel
Research team(s)
Project type(s)
- Research Project
Using novel molecular approaches to understand the transmission dynamics of Mycobacterium leprae in the Comoros.
Abstract
Leprosy is a serious mutilating disease and although Mycobacterium leprae was the first human pathogen discovered, the precise way of spreading between humans remains a mystery. This is part of the reason why leprosy control fails despite the availability of effective treatments. Over 200,000 new leprosy patients are diagnosed worldwide each year, and the high proportion in children indicates its ongoing spread. To stop transmission chains once and for all, new approaches to leprosy control are needed. Therefore, this study will revisit fundamental questions regarding transmission in an innovative way. Firstly, we will evaluate minimally invasive, field-friendly tests to quantify the bacillary load in each patient and correlate with the effectiveness of treatment and the identification of the most infectious patients. In this study, we will be the first to apply targeted Next Generation Sequencing of M. leprae. Within the ongoing "ComLep" study in the Comoros, we will classify the bacteria in M. leprae subtypes and associate them with the GPS data of each patient's house, to identify transmission links. Once these transmission chains have been established, we can determine define where transmission occurs and if a reservoir of asymptomatic people is sustaining transmission of the disease. This in turn will inform which contacts should receive leprosy preventive therapy. These findings will inform optimal control strategies to eliminate leprosy in the Comoros and elsewhere.Researcher(s)
- Promoter: Rigouts Leen
- Fellow: Braet Sofie
Research team(s)
Project type(s)
- Research Project
Identification of novel resistance mechanisms against clofazimine in Mycobacterium tuberculosis.
Abstract
Increasing resistance of Mycobacterium tuberculosis to antibiotics plays a crucial role in the current epidemiology of tuberculosis (TB). Because of, amongst others, inadequate treatment of multi-drug resistant (MDR) TB - with resistance to isoniazid and rifampicin - the incidence of extreme-drug resistant (XDR) TB - defined as MDR-TB with additional resistance to fluoroquinolones (FQ) and one of the injectable second-line antibiotics - worldwide. Clinical studies show that the use of FQs is necessary for successful MDR-TB treatment. Clofazimin (CLOF) is also being used more and more in the standard treatment of MDR-TB. Clinical CLOF-resistant M. tuberculosis isolates have been poorly described to date and the resistance mechanisms are insufficiently known. It is suspected that CLOF provides an increased release of lysophospholipids on the one hand and superoxide and hydrogen peroxide on the other, resulting in bacterial cell death. The molecular mechanism behind the potential effect of CLOF is not well known, but efflux pumps may play a role in resistance. The proposed study aims to identify new resistance mechanisms for two antibiotics that form the pillars of MDR-TB treatment.Researcher(s)
- Promoter: Rigouts Leen
- Fellow: Coeck Nele
Research team(s)
Project type(s)
- Research Project
Research for new mechanisms of resistance in fluorochinolone resistant Mycobacterium tuberculosis.
Abstract
This project represents a formal research agreement between UA and on the other hand EU. UA provides EU research results mentioned in the title of the project under the conditions as stipulated in this contract.Researcher(s)
- Promoter: Rigouts Leen
- Fellow: Coeck Nele
Research team(s)
Project type(s)
- Research Project