THE AETIOLOGY AND EPIDEMIOLOGY OF NONTUBERCULOUS MYCOBACTERIA (NTM) IN AUSTRALIANS WITH CF

Abstract

Introduction: Nontuberculous mycobacterial (NTM) infections have rapidly emerged in people with CF (pwCF), threatening survival. Here, we aim to understand the epidemiology and risk of NTM infection in pwCF in Australia. Methods: 18 CF Centres prospectively collected respiratory samples for NTM culture from pwCF (baseline, 6 months, 1 year, then annual to 4 years) (2016-2021); associated clinical, microbiological, geographic and social data was supplied by the clinic and linkage with Australian CF Data Registry. NTM pulmonary disease (PD) based on ATS micro criteria. Bayesian geostatistical modelling, incorporating environmental/climatic variables along with spatial random effects, was applied to generate predictive maps identifying high-risk areas for NTM in Australian CF patients. Results: Similar prevalence rates of Mycobacterium avium complex (MAC) and Mycobacterium abscessus (Mabs) occurred (-8%), Mabs progressed to PD more frequently than MAC (37.8% and 12.3%, respectively (p < 0.01)). Risk of isolating Mabs is 2-4 times higher in participants <25 years compared to participants >25 years (p < 0.05-0.001). Isolation of pathogenic NTM species was reduced by chronic Pseudomonas aeruginosa infection (Mabs Odds Ratio (OR) 0.4, Confidence Interval (CI) 0.2-0.7, p < 0.001; MAC OR 0.6, CI 0.4-0.9, p < 0.01) and macrolide prescription (Mabs OR 0.5, CI 0.3-0.8). Environmental factors associated with the occurrence of MAC include the proportion of cropland cover (OR = 7.55; 95% Credible Interval (CrI): 1.74, 32.88) and bareland cover (OR = 0.012; 95% CrI: 0.002, 0.56). Mabs was positively associated with the proportion of grassland cover (OR = 3.25; 95% CrI: 1.11, 9.51), while higher elevation was negatively associated with Mabs occurrence (OR = 0.98; 95% CrI: 0.96, 0.99). Conclusion: NTM infection in pwCF is common. The frequency of NTM was negatively associated with macrolide use and P. aeruginosa infection. Geospatial analysis highlights that environmental risks vary for different NTM species.