A global update on rare non-tuberculous mycobacteria in humans: epidemiology and emergence

Non-tuberculous mycobacteria (NTM) have evolved as an emerging group of pathogens globally. Due to the pitfalls in identification, the majority of them are not familiar or remain 'rare' to clinicians and microbiologists. In available literatures, a consolidated global data analysis is non-existent on rarely encountered NTM. A systematic review and meta-analysis have been carried out on 100 rare NTM species, which are possibly identified only by DNA sequencing methods, to establish their global epidemiology, emergence and clinical relevance. Articles published in English from 1956 to 2018 reporting rare NTM species were searched in MEDLINE, Scopus, Ovid and Embase. A total of 447 articles matched the selection criteria, and 1670 rare NTM cases were identified from 52 countries. The majority of the incidences were reported from North America (33.4%), followed by Europe (23.8%) and Asia (20.8%). Of 100 species, 43 were defined as emerging species, with 1351 (80.9%) new incidence cases globally. In total, 87 species caused clinically relevant pulmonary and extrapulmonary diseases. Interestingly, some NTM species showed significant geographic predominance, such as M. conceptionense to South Korea, M. shinjukuense to Japan; M. arupense and M. non-chromogenicum to the United States and M. riyadhense to Saudi Arabia. Rare NTM species mainly caused pulmonary infection (67.1%), while extrapulmonary infections generally comprised mycobacteremia and skin/soft tissue infections. In conclusion, the majority of rarely encountered NTM species are now well-established pathogens with valid clinical implications. The emergence of these rare pathogens warrants immediate local and international follow-ups. Their increasing clinical and pathological significance should not be disregarded.