Impact van vertragingen bij de diagnose en korte behandelingsregimes op de resultaten bij patiënten met rifampicine-resistente tuberculose in Kameroen

Supervisors: Prof. dr. Tom Decroo (ITM) Prof. dr. Emmanuel André (KU Leuven/UZ Leuven) Prof. Palmer Masumbe Netongo (Université of Yaoundé I, Cameroon) Prof. dr. em. baroness Lut Lynen (former director ITM) Abstract: My thesis aimed to identify the gaps in RR-TB diagnosis and treatment in Cameroon and suggest areas for improvement. In the first objective, using spatial analysis and mathematical modelling, I identified regions with probable low TB and RR-TB notification, including the corrected national TB and RR-TB diagnostic gap for each of the ten regions. Considering that at present, 58% and 28% of WHO-estimated TB and RR-TB patients are being diagnosed, this result could support the efficient allocation of available rapid molecular diagnostic tools nationwide. This may greatly impact closing both TB and RR-TB diagnostic gaps. In the second objective, using a systematic review and meta-analysis, I showed that in high TB/HIV burden countries(including Cameroon), after more than a decade of implementation of the Xpert MTB/RIF as point-of-care TB diagnosis, up to 18% (95%CI: 12-25)% of diagnosed RR-TB patients do not start treatment (most studies being routine program data) while reasons were not systematically reported. Therefore, it will be essential in Cameroon to routinely report pre-treatment attrition in all patients diagnosed with RR-TB, along with the reasons for not starting treatment, to tailor future interventions aimed at closing the RR-TB pre-treatment gap. Finally, in the last objective, using nationwide data over five years, I demonstrated the importance of addressing missing second-line DST data (29.6% in this cohort) for key TB drugs (quinolones and injectables) used to manage RR-TB as a key predictor of mortality. This should definitely be a priority when constructing effective regimens, including using bedaquiline, to sustain high treatment success while safeguarding resistance acquisition to the core drugs used. In summary, my work provides efficient methods for improving the RR-TB diagnostic and therapeutic pathway in Cameroon. More efficient use of diagnostic means may substantially increase RR-TB notification. Identifying the RR-TB pre-treatment gap and its determinants will make the RR-TB programme more effective. Access to DST for the most important second-line drugs will improve treatment outcomes. Altogether, these interventions will contribute to better RR-TB control in Cameroon.