Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are

mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') a ...

which do not cause

tuberculosis Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...

or leprosy/Hansen's disease. NTM can cause pulmonary diseases that resemble tuberculosis. Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans, and are commonly found in soil and water.

Introduction

Mycobacteria are a family of small, rod-shaped bacilli that can be classified into three main groups for diagnosis and treatment: * ''Mycobacterium tuberculosis'' complex, which can cause

: ''

M. tuberculosis ''Mycobacterium tuberculosis'' (M. tb), also known as Koch's bacillus, is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' ha ...

'', '' M. bovis'', '' M. africanum'', '' M. microti'' and '' M. canettii'' * ''

M. leprae ''Mycobacterium leprae'' (also known as the leprosy bacillus or Hansen's bacillus) is one of the two species of bacteria that cause Hansen's disease (leprosy), a chronic but curable infectious disease that damages the peripheral nerves and targ ...

'' and '' M. lepromatosis'', which cause Hansen's disease, also called

leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respir ...

* Nontuberculous mycobacteria (NTM) are all the other mycobacteria that can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease. Although over 150 different species of NTM have been described, pulmonary infections are most commonly due to ''Mycobacterium avium'' complex (MAC), ''Mycobacterium kansasii'', and '' Mycobacterium abscessus'' (see image).

Taxonomy

In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups ( Runyon classification):Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), ''Medical Microbiology'' (17th ed.), pp. 221–227. Elsevier. , p. 221 *Photochromogens develop pigments in or after being exposed to light. Examples include '' M. kansasii'', ''M. simiae'', and '' M. marinum''. *Scotochromogens become pigmented in darkness. Examples include '' M. scrofulaceum'' and ''M. szulgai''. *Nonchromogens include a group of prevalent opportunistic pathogens called ''M. avium'' complex (MAC). Other examples are ''M. ulcerans'', '' M. xenopi'', '' M. malmoense'', ''M. terrae'', '' M. haemophilum'', and '' M. genavense''.Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), ''Medical Microbiology'' (17th ed.), pp. 221–227. Elsevier. ., p. 222 *Rapid growers include four well-recognized, pathogenic, rapidly growing, nonchromogenic species: '' M. chelonae'', '' M. abscessus'', '' M. fortuitum'', and ''M. peregrinum''. Other examples cause disease rarely, such as '' M. smegmatis'' and '' M. flavescens''. The number of identified and cataloged NTM species has been increasing rapidly, from about 50 in 1997 to over 125 by January 2007. The surge is mainly due to improved isolation and identification techniques. Even with these new techniques, though, the Runyon classification is sometimes used to organize the mycobacteria into categories.

Epidemiology

NTM are widely distributed in the environment, particularly in wet soil, marshland, streams, rivers, and estuaries. Different species of NTM prefer different types of environments. Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), ''Medical Microbiology'' (17th ed.), pp. 221–227. Elsevier. .p. 226" Human disease is believed to be acquired from environmental exposures. Unlike tuberculosis and leprosy, animal-to-human or human-to-human transmission of NTM rarely occurs. NTM diseases have been seen in most industrialized countries, where incidence rates vary from 1.0 to 1.8 cases per 100,000 persons. Recent studies, including one done in Ontario, Canada, suggest that incidence is much higher. Pulmonary NTM is estimated by some experts in the field to be at least ten times more common than TB in the U.S., with at least 150,000 cases per year. Most NTM disease cases involve the species known as ''

Mycobacterium avium complex ''Mycobacterium avium ''complex is a group of mycobacteria comprising ''Mycobacterium intracellulare'' and ''Mycobacterium avium'' that are commonly grouped because they infect humans together; this group, in turn, is part of the group of nontub ...

'' or MAC for short, ''M. abscessus'', ''M. fortuitum'' and ''M. kansasii''. ''M. abscessus'' is being seen with increasing frequency and is particularly difficult to treat.American Thoracic Society, p. 370

Mayo Clinic Mayo Clinic () is a Nonprofit organization, private American Academic health science centre, academic Medical centers in the United States, medical center focused on integrated health care, healthcare, Mayo Clinic College of Medicine and Science ...

researchers found a three-fold increased incidence of cutaneous NTM infection between 1980 and 2009 in a population-based study of residents of Olmsted County, Minnesota. The most common species were ''M. marinum'', accounting for 45% of cases and ''M. chelonae'' and ''M. abscessus'', together accounting for 32% of patients. ''M. chelonae'' infection outbreaks, as a consequence of tattooing with infected ink, have been reported in the United Kingdom and the United States. Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery), and pulmonary infections.

Pathogenesis

The most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, and disseminated diseases are also important. Pulmonary disease caused by NTM is most often seen in postmenopausal women and patients with underlying lung diseases such as

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

bronchiectasis Bronchiectasis is a disease in which there is permanent enlargement of parts of the bronchi, airways of the lung. Symptoms typically include a chronic cough with sputum, mucus production. Other symptoms include shortness of breath, hemoptysis, co ...

, and prior

. It is not uncommon for

alpha 1-antitrypsin deficiency Alpha-1 antitrypsin deficiency (A1AD or AATD) is a genetic disorder that may result in lung disease or liver disease. Onset of lung problems is typically between 20 and 50 years of age. This may result in shortness of breath, wheezing, or an inc ...

Marfan syndrome Marfan syndrome (MFS) is a multi-systemic genetic disorder that affects the connective tissue. Those with the condition tend to be tall and thin, with dolichostenomelia, long arms, legs, Arachnodactyly, fingers, and toes. They also typically ha ...

, and

primary ciliary dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, fallopian tube, and flagella of spe ...

patients to have pulmonary NTM colonization and/or infection. Pulmonary NTM can also be found in individuals with

AIDS The HIV, human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a Preventive healthcare, pr ...

and malignant disease. It can be caused by many NTM species, which depends on region, but most frequently MAC and ''M. kansasii''.Grange, p. 225 Clinical symptoms vary in scope and intensity but commonly include chronic cough, often with purulent sputum. Hemoptysis may also be present. Systemic symptoms include malaise, fatigue, and weight loss in advanced disease. The diagnosis of ''M. abscessus'' pulmonary infection requires the presence of symptoms, radiologic abnormalities, and microbiologic cultures.

Lymphadenitis Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...

can be caused by various species that differ from one place to another, but again, MAC is the main cause worldwide. Most patients are aged less than 5 years, but the incidence is rare for children having

BCG vaccine The Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recom ...

. The disease has a high curability.Grange, p. 223 Soft-tissue disease due to NTM infection include post-traumatic abscesses (caused by rapid growers), swimming pool granuloma (caused by ''M. marinum'') and

Buruli ulcer Buruli ulcer () is an infectious disease characterized by the development of painless open wounds. The disease is limited to certain areas of the world, with most cases occurring in Sub-Saharan Africa and Australia. The first sign of infection i ...

(caused by ''M. ulcerans'' or ''M. shinshuense''). Post-traumatic abscesses most commonly occur after injection. Disseminated mycobacterial disease was common in US and European AIDS patients in the 1980s and early 1990s, though the incidence has declined in developed nations since the introduction of highly active antiretroviral therapy. It can also occur in individuals after having renal transplantation.

Diagnosis

Nontuberculous Mycobacterial Infection on neck and chest

Diagnosis of opportunistic mycobacteria is made by repeated isolation and identification of the pathogen with compatible clinical and radiological features. Similar to ''M. tuberculosis'', most nontuberculous mycobacteria can be detected microscopically and grow on Löwenstein-Jensen medium. Many reference centres now use a nucleic acid-based method such as sequence differences detection in the gene coding for

16S ribosomal RNA 16S ribosomal RNA (or 16 S rRNA) is the RNA component of the 30S subunit of a prokaryotic ribosome ( SSU rRNA). It binds to the Shine-Dalgarno sequence and provides most of the SSU structure. The genes coding for it are referred to as 16S ...

to identify the species. Pulmonary NTM disease diagnosis requires both identification of the mycobacterium in the patient's lung(s), as well as a high-resolution CT scan of the lungs.

Research

French researchers finalized the genome sequence of ''M. abscessus'' in March 2008. The genome is available at https://www.ncbi.nlm.nih.gov/sites/entrez?db=genome&cmd=search&term=abscessus.

References

External links

NTM Info & Research, a nonprofit research and patient support organizationLung, Nontuberculous Mycobacterial Infections from eMedicine Radiology
{{Mycobacteria Bacteriology Bacterial diseases