## 5 Mycobacteria Infection
### Clinically-Relevant Species  
Due to their environmental nature, NTM mycobacteria are distributed worldwide, however, several knowledge gaps remain, namely concerning disease incidence across countries and continents, as disease notification is not mandatory. A prevalence report of NTM in pulmonary samples evidenced a differential distribution, with MAC, _M. xenopi_, _M. fortuitum_, and _M. abcessus_ dispersed throughout the globe, and _M. kansasii_ and _M. malmoense_ with a higher incidence in Europe [180]. Overall, _M. ulcerans_, MAC, _M. kansasii_, _M. malmoense_, _M. abscessus_, _M. chelonae_, _M. fortuitum_, _M. xenopi_, and _M. marinum_ are globally the most clinically relevant groups. _M. ulcerans_ causes the third most common mycobacterial disease in the world, the Buruli ulcer, following TB and leprosy, with a total of 2713 cases reported in 2018, mainly in countries from West and Central Africa [253]. _M. ulcerans_ affects mainly skin and bone, and the clinical presentation can vary from a localized nodule or ulcer to generalized ulcerative or nonulcerative disease, leading to long-term disability [252]. The transmission pathway to humans is unknown, however, evidence suggests that mild skin injury after exposure to contaminated environmental sources, such as water or soil, can be a transmission route [252]. MAC currently encompasses 14 members, being _M. avium_ subspecies _avian_ (MAA), MAP, MAH, _M. intrracellular_, and _M. chimera_ the most clinically relevant members [254]. MAC can survive in several environmental conditions, isolated from water systems in residences and hospitals, and is the most common NTM associated with lung disease worldwide [255]. Cutaneous involvement of MAC infections has been rarely reported, with the infection been a result of trauma, cosmetic procedures, and postsurgical infections [251]. Several reports indicate a tendency to increase the prevalence of MAC species in the USA, Europe, and South Korea [256]. MAA is also connected to lymphadenitis in young children; and _M. chimera_ was recently implicated in disease in patients subjected to cardiac surgery [257]. MAP causes a chronic granulomatous enteric infection in ruminants, mainly cattle, named [PERSON]'s disease, and has a long-term hypothesized association with [PERSON]'s disease in humans. _M. kansasi_ is responsible for pulmonary disease with nodular bronchiectasis and fibrocavitary forms of clinical presentation, being the second most common cause of NTM lung disease in some European countries and the USA [255,258]. However, individuals with extra-pulmonary and disseminated disease were already reported [258]. Patients with previous lung conditions like COPD, bronchiectasis, or tumors are group risks [258]. Furthermore, in immunocompromised patients with HIV infection or subjected to renal transplantation, _M. kansasi_ can upsurge as a cutaneous infection as well, sometimes in a concomitant way, or even as a disseminated disease episode [258]. The tap water is pointed out as the main reservoir of _M. kansasi_ and the contamination occurs through aerosol inhalation [255,258]. However, despite this species being considered as an environmental opportunistic pathogen, the strains associated with human infections have not yet been isolated from environmental samples, which suggests a different source of infection [258]. _M. malmoense_ is responsible for causing pulmonary disease with a clinical presentation similar to TB [259]. A few reports of lymphadenitis in children and tenosynovitis by _M. malmoense_ were reported by the medical community [252]. The isolation from water and soil is reported in the literature, however, the environmental sources are not well defined. _M. malmoense_ infection is frequently reported in the UK and northern Europe [176]. Nowadays, genomic data support the classification of _M. abscessus_ in _M. abscessus_ subsp. _abscessus_, _M. abscessus_ subsp. _bolletii_, and _M. abscessus_ subsp. _massiliense_[260].