PhD defence Souleymane Hassane Harouna

Supervisors

• Prof. dr. Bouke C. de Jong (ITM)

• Prof. dr. Leen Rigouts (ITM/University of Antwerp)

Abstract

Tuberculosis (TB) is a contagious disease caused by the Mycobacterium tuberculosis complex (MTBc) posing a global health challenge, particularly with drug-resistant TB (DR-TB) detection and treatment. Indeed, despite global efforts, only about 43% of DR-TB cases are diagnosed and treated, with a 68% treatment success rate for the World Health Organization (WHO) 2021 cohort. This thesis aimed to enhance the diagnosis and management of multidrug-resistant TB (MDR-TB) in Guinea by testing novel diagnostic approaches and improving therapeutic strategies. To achieve our objectives, we conducted two diagnostic studies and to therapeutic studies

Chapter II explored face mask sampling (FMS) as a minimally invasive method for pulmonary TB diagnosis among symptomatic patients. FMS results, compared to sputum samples analyzed by the Xpert MTB/RIF and Xpert MTB/RIF Ultra (Xpert Classic and Xpert Ultra), showed moderate agreement (kappa value of 0.47), with overall low sensitivity (48.1%) but high specificity (95.7%). While Xpert Ultra yielded higher sensitivity than Xpert Classic (60.2% vs 38.0%), Xpert Classic had superior specificity (100% vs 90.6%).

Following these mitigated results, we explored in Chapter III tongue swabbing (TS) with Xpert Ultra and in-house swab IS6110-qPCR as another minimally invasive diagnostic approach. In a prospective study, single TS showed lower sensitivity (88.5%) than sputum, although pooling swabs improved sensitivity to 93.8%. Furthermore, bacillary load of positive TS samples was not affected by the sampling order, and "MTB low" results were predominant for both single and pooled series of TS. Sample adequacy control via qPCR assay detected human mitochondrial DNA and thus confirmed the oral source of TS samples. In a retrospective analysis, the agreement between the in-house swab IS6110-qPCR and sputum-Xpert was high (k=0.91 for Xpert Classic and k=0.86 for Ultra).

Chapter IV addressed MDR-TB treatment with a longer regimen (lasting 18-20 months) and a shorter regimen (9-11 months) outcomes in a post-Ebola setting. Results showed that patients on a shorter regimen were more likely to achieve successful treatment outcome (74.0% vs. 58.7%) and less likely to experience adverse events (loss to follow-up, death or treatment failure), with a two-fold increase in risk for those on a longer regimen (aOR: 2.5).

In Chapter V, community supported self-administered TB treatment (CS-SAT) and active TB screening among household contacts were evaluated. CS-SAT achieved a 94.7% favorable outcome, exceeding the national target of 90%. Active household screening enabled the referral of 376 children for isoniazid preventive therapy and the detection of five pulmonary confirmed TB among household contacts.

Our studies contributed to enhancing TB diagnosis and treatment. Findings suggest that further diagnostic studies using the new sampling approches are need for pulmonary TB diagnosis. Children and paucibacillary group patients should be prioritized for such studies. For MDR-TB treatment, shorter regimens should be prioritized. Additionally, enhancing the technical capacity of laboratories and medical services is crucial to ensure improved outcomes. Finally, community-supported TB treatment should be tailored to specific contexts and patient needs, to guarantee the continuity of the patient treatment