Epidemiological and molecular characterization of clinically relevant non-tuberculous mycobacteria in the Western Cape, South Africa, 2016–2022

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Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms increasingly recognised as opportunistic pathogens. Although the global burden of NTM disease is increasing, epidemiological data from sub-Saharan Africa remain limited. This study aimed to investigate the epidemiology of NTM in the Western Cape province of South Africa. Mycobacteria cultures ( n = 3,385) with a GenoType Mycobacterium Common Mycobacteria and Additional Species line probe assay were retrospectively screened for NTM between 2016 and 2022. Temporal incidence, species distribution, demographic characteristics, specimen type distribution, time-to-positivity, spatial–temporal analysis, clinical associations, and antimicrobial exposure were analysed using descriptive and univariable statistical approaches. Geographic mapping was performed using ArcGIS. A total of 684 clinically relevant NTM cases were identified. Annual incidence increased from 0.47/100,000 population (95% confidence interval [CI]: 0.33–0.65) in 2016 to 1.88/100,000 (95% CI: 1.59–2.22) in 2020. Mycobacterium intracellulare (285/684, 41.7%) and Mycobacterium avium (187/684, 27.3%) predominated, with infections occurring mainly in adults aged 18–64 years (median: 41; interquartile range: 31–52). Extrapulmonary specimens represented 41.5% (284/684). Among these, blood cultures (BC) comprised 96/284 (33.8%), with Mycobacterium avium responsible for 81.3% (78/96) of NTM-related BC cases. Mycobacterium avium was associated with increased odds of human immunodeficiency virus (HIV) infection (odds ratio [OR] 5.74, 95% CI: 3.39–9.72) and one-year all-cause mortality (OR 3.38, 95% CI: 2.13–5.36) compared with Mycobacterium intracellulare . Extrapulmonary disease was associated with significantly higher one-year all-cause mortality than pulmonary disease (36.4% vs. 23.8%; p = 0.004). At the species level, a significant difference in extrapulmonary versus pulmonary disease was observed only for Mycobacterium kansasii , which was associated with higher mortality (54.5% vs. 12.5%; p = 0.018). Recurrent NTM cases were mainly associated with the Mycobacterium avium complex, accounting for 80.8% (173/214) of these cases. Spatial–temporal mapping showed a heterogeneous distribution across the province, with no statistically significant temporal clustering at the suburb level. Descriptive spatial analysis identified four municipalities and one district (Cape Winelands) with higher-than-expected observed case numbers during the study period. Antimicrobial exposure varied by species, with frequent macrolide-based regimens for Mycobacterium avium complex and broader multidrug regimens for rapidly growing NTM. NTM disease represents a growing clinical and public health concern in South Africa. Increasing detection, substantial extrapulmonary disease burden, and species-specific clinical heterogeneity highlight the need for improved diagnostic confirmation, expanded molecular identification, and enhanced antimicrobial stewardship. Strengthened surveillance is required to optimise NTM disease management in high tuberculosis- and HIV-burden settings.

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