The upcoming challenge of non-tuberculous mycobacterial pulmonary disease and tuberculosis/non-tuberculous mycobacteria co-infection in Ghana and Sub-Saharan Africa

Nontuberculous mycobacteria (NTM) are increasingly detected in tuberculosis (TB)-endemic regions, yet their clinical significance remains poorly defined. In sub-Saharan Africa (SSA), limited diagnostic capacity and absence of guidelines contribute to uncertainty in patient management. This PhD research combined (i) a systematic scoping review of NTM in SSA, (ii) a retrospective laboratory analysis of 2,492 sputum samples in Ghana (2012–2021), (iii) a retrospective cohort of 380 MDR/RR-TB patients in Ghana (2018–2021), and (iv) three prospective cohort studies involving 9,981 symptomatic individuals in Ghana, Nigeria, and Niger. Standard mycobacterial culture, MPT64 antigen testing, line probe assays, and sequencing were used for species identification. Clinical and radiological data were analysed against international ATS/IDSA/ERS/ESCMID criteria for NTM pulmonary disease (NTM-PD). The scoping review highlighted major gaps: most SSA studies did not apply international diagnostic criteria, species-level identification was rare, and MPT64 antigen misclassified Mycobacterium tuberculosis complex (MTBc) as NTM. In Ghana, retrospective laboratory analysis showed 33.7% culture positivity. Initially, 30.6% were presumed NTM, but only 53 isolates (23.6%) were confirmed after molecular speciation, reducing the prevalence to 2%. M. intracellulare (66%) predominated, while 18 MTBc isolates, including M. africanum, were misclassified as NTM by MPT64. Four patients fulfilled NTM-PD criteria, all previously treated as RR-TB. Among 380 MDR/RR-TB patients, 7.1% had NTM isolated, mainly M. intracellulare and M. fortuitum. Treatment success was 67.9%, higher with all-oral bedaquiline regimens (71.4%) compared to injectable-containing regimens (60.3%). HIV was associated with unfavourable outcomes (aOR 1.80, 95% CI 1.05–3.11), while NTM isolation itself was not. Geographic variation showed higher odds of NTM isolation in Eastern (aOR 15.68) and Brong Ahafo regions (aOR 4.74). In the prospective cohorts, 99/938 (10.6%) had NTM isolated. Predominant species were M. intracellulare (34.3%), M. fortuitum (16.2%), and M. abscessus (10.1%). Among patients with ≥2 sputum samples, 15 (30.6%) met NTM-PD criteria, with 20% mortality. Unique isolates such as M. palustre were detected only by sequencing, reflecting diagnostic limitations of commercial assays. This thesis demonstrates that although NTM are frequently isolated among presumed TB patients in West Africa, their presence did not adversely affect MDR/RR-TB treatment outcomes in Ghana, while their clinical significance remains challenging to determine due to limited repeated culture data from SSA. These findings underscore the need to strengthen laboratory capacity for species-level identification, integrate molecular diagnostics into routine algorithms, and develop regional clinical guidelines for the diagnosis and management of NTM-PD, while systematically excluding TB.