Nontuberculous Mycobacteria

Etiology

NTM are ubiquitous in the environment all over the world, existing as saprophytes in soil and water (including municipal water supplies, tap water, hot tubs, and shower heads), environmental niches that are the supposed sources of human infections. With the introduction of molecular identification tools such as 16S recombinant DNA gene sequencing, the number of identified NTM species has grown to more than 150; the clinical relevance (i.e., percentage of isolates that are causative agents of true NTM disease, rather than occasional contaminants) differs significantly by species.

Mycobacterium avium complex ( MAC ; i.e., M. avium , Mycobacterium intracellulare, and several closely related but rarer species) and Mycobacterium kansasii are most often isolated from clinical samples, yet the isolation frequency of these species differs significantly by geographic area. MAC bacteria have been frequently isolated from natural and synthetic environments, and cases of MAC disease have been successfully linked to home exposure to shower and tap water. Although the designation M. avium suggests that human infections are acquired from birds (Latin avium ), molecular typing has established that M. avium strains that cause pediatric lymphadenitis and adult pulmonary disease represent the M. avium hominis suis subgrouping, mainly found in humans and pigs and not in birds.

Some NTM have well-defined ecologic niches that help explain infection patterns. The natural reservoir for Mycobacterium marinum is fish and other cold-blooded animals, and the fish tank granuloma , a localized skin infection caused by M. marinum, follows skin injury in an aquatic environment. Mycobacterium fortuitum complex bacteria and Mycobacterium chelonae are ubiquitous in water and have caused clusters of nosocomial surgical wound and venous catheter–related infections . Mycobacterium ulcerans is associated with severe, chronic skin infections ( Buruli ulcer disease ) and is endemic mainly in West Africa and Australia, although other foci exist. Its incidence is highest in children <15 yr old. M. ulcerans had been detected in environmental samples by polymerase chain reaction (PCR) but was only recently recovered by culture from a water strider (an insect of the Gerris genus) from Benin.

Epidemiology

Humans are exposed to NTM on a daily basis. In rural U.S. counties, where M. avium is common in swamps, the prevalence of asymptomatic infections with M. avium complex, as measured by skin test sensitization, approaches 70% by adulthood. Still, the incidence and prevalence of the various NTM disease types remain largely unknown, especially for pediatric NTM disease. In Australian children the overall incidence of NTM infection is 0.84 per 100,000, with lymphadenitis accounting for two thirds of cases. The incidence of pediatric NTM disease in the Netherlands is estimated at 0.77 infections per 100,000 children per year, with lymphadenitis making up 92% of all infections.

In comparison, estimations of the prevalence of NTM from respiratory samples in adults are 5-15 per 100,000 persons per year, with important differences between countries or regions. Because pulmonary NTM disease progresses slowly, over years rather than months, and usually takes several years to cure, the prevalence of pulmonary NTM disease is much higher than incidence rates would suggest.

The paradigm that NTM disease is a rare entity limited to developed countries is changing. In recent studies in African countries with a high prevalence of HIV infection, it has been found that NTM might play a much larger role as a cause of tuberculosis-like disease of children and adults than previously assumed and thus confuse the diagnosis of tuberculosis.

Although it is generally believed that NTM infections are contracted from environmental sources, recent whole genome sequence analysis of Mycobacterium abscessus strains of patients in a cystic fibrosis (CF) clinic in the United Kingdom has raised the possibility of nosocomial transmission among CF patients.