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'') and ...

which do not cause

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...

leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...

(also known as Hansen's disease). NTM do 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 the purpose of diagnosis and treatment: * ''Mycobacterium tuberculosis'' complex, which can cause

: '' M. tuberculosis'', '' M. bovis'', '' M. africanum'', '' M. microti'' and '' M. canetti'' * ''

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 a ...

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

* 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 ''Mycobacteroides abscessus'' (formerly ''Mycobacterium abscessus'') is a species of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that is a common soil and water contaminant. Although ''M. abscessus'' most commonly causes ch ...

'' (see image).

Taxonomy

In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (

Runyon classification The Timpe and Runyon classification of nontuberculous mycobacteria based on the rate of growth, production of yellow pigment and whether this pigment was produced in the dark or only after exposure to light. It was introduced by Ernest Runyon i ...

):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 ''Mycobacterium xenopi'' is a slow-growing scotochromogenic species of ''Mycobacterium''. It was first reported by Schwabacher in 1959, having been isolated in lesions found on a ''Xenopus laevis'', but the possibility of human infection was n ...

'', '' M. malmoense'', ''M. terrae'', '' M. haemophilum'', and ''

M. genavense Mycobacterium genavense is a slow-growing species of the phylum Actinomycetota (Gram-positive bacteria with high guanine and cytosine content, one of the dominant phyla of all bacteria), belonging to the genus ''Mycobacterium''. Description ...

''.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 ''Mycobacterium fortuitum'' is a nontuberculous species of the phylum Actinomycetota (Gram-positive bacteria with high guanine and cytosine content, one of the dominant phyla of all bacteria), belonging to the genus ''Mycobacterium''. Backgrou ...

'', 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 still 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 environment. 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 The Mayo Clinic () is a nonprofit American academic medical center focused on integrated health care, education, and research. It employs over 4,500 physicians and scientists, along with another 58,400 administrative and allied health staf ...

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 disease such as

cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Ot ...

bronchiectasis Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest ...

, 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 ...

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 long arms, legs, fingers, and toes. They also typically have exceptionally flexible joints a ...

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

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...

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 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 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 Swimming is the self-propulsion of a person through water, or other liquid, usually for recreation, sport, exercise, or survival. Locomotion is achieved through coordinated movement of the limbs and the body to achieve hydrodynamic thrust that r ...

(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, most cases occurring in Sub-Saharan Africa and Australia. The first sign of infection is a ...

(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 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

The NTM Handbook: A Guide for Patients with Nontuberculous Mycobacterial Infections Including MACNTM Info & Research, a nonprofit research and patient support organization
** NTMinfo produce
this 21-page PDF entitled "Insight -- A Patient's Perspective" and vetted by experts in 2014Stop NTM NowNational Jewish Medical and Research CenterUniversity of Texas, Tyler Health Center
* ttp://ait-pharm.com/ntm/ A guide for patients and clinicians - AIT Therapeutics {{Mycobacteria Bacteriology Bacterial diseases