Nontuberculous mycobacteria

Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria^[1] and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis or Hansen's disease (also known as leprosy).

Introduction

Mycobacteria are a family of small, rod-shaped bacilli that can be classified into 3 main groups for the purpose of diagnosis and treatment:

• Mycobacterium tuberculosis complex which can cause tuberculosis: M. tuberculosis, M. bovis, M. africanum, M. microti and M. canetti.
• M. leprae which causes Hansen's disease or leprosy.
• Nontuberculous mycobacteria (NTM) are all the other mycobacteria which can cause pulmonary disease resembling tuberculosis, lymphadenitis, skin disease, or disseminated disease.

Taxonomy

In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (Runyon classification):^[2]

• Photochromogens, which develop pigments in or after being exposed to light. Examples include M. kansasii, M. simiae and M. marinum.^[2]
• Scotochromogens, which become pigmented in darkness. Examples include M. scrofulaceum and M. szulgai.^[2]
• Non-chromogens, which includes 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.^[3]
• Rapid growers include four well recognized pathogenic rapidly growing non-chromogenic species: M. chelonae, M. abscessus, M. fortuitum and M. peregrinum. Other examples cause disease rarely, such as M. smegmatis and M. flavescens.^[3]

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 technique.^[4]

However, even with these new techniques, the Runyon classification is still sometimes used to organize the mycobacteria into categories.^[5]

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.^[6] Human disease is believed to be acquired from environmental exposures, and unlike tuberculosis and leprosy, there has been no evidence of animal-to-human or human-to-human transmission of NTM, hence the alternative label "environmental bacteria".^[7]

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 MAC, M. abscessus, M. fortuitum and M. kansasii. M. abscessus is being seen with increasing frequency and is particularly difficult to treat. ^[7]

Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery) and pulmonary infections. ^[8]

Pathogenesis

The most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, and disseminated disease are also important.^[7]

Pulmonary disease caused by NTM is most often seen in post-menopausal women. It is not uncommon for Cystic Fibrosis, Alpha-1, Marfan's and Primary Ciliary Dyskenesia patients to have pulmonary NTM colonization and/or infection. Pulmonary NTM can also be found in individuals with AIDS and malignant disease. It can be caused by many NTM species which depends on region, but most frequently MAC and M. kansasii.^[9]

Lymphadenitis can be caused by various species that is different from one place to another; but again, MAC is the main cause worldwide. Most patient are aged less than 5 years, but the incidence is rare for children having BCG vaccine. The disease has a high curability.^[10]

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 (caused by M. ulcerans or M. shinshuense). Post-traumatic abscesses most commonly occur after injection.^[10]

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.^[9]

Diagnosis

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.^[9] 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.^[6]

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

Virginia Tech is conducting a home water supply and patient sputum comparison study to determine source of infection in pulmonary NTM cases. This study was funded by NTM Info & Research and results will be available by mid-2009. http://www.ntminfo.org/default_aspx/p/research.aspx

An epidemiology study on pulmonary NTM is currently being conducted by National Institute of Allergy & Infectious Disease and Kaiser Permanente in southern California. Results will be available by mid-2009. This study was funded by NTM Info & Research.

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

McGill University in Montreal, Canada is conducting a study to determine the genome sequence (type strain) of M. avium intracellulare. This study is partially funded by NTM Info & Research and results will be available by late 2009.

Notes

1. ^ MeSH Atypical+Mycobacteria
2. ^ ^{a b c} Grange, p. 221
3. ^ ^{a b} Grange, p. 222
4. ^ American Thoracic Society, p.369
5. ^ Tortoli E (April 2003). "Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s". Clinical microbiology reviews 16 (2): 319–54. doi:10.1128/CMR.16.2.319-354.2003. PMC 153139. PMID 12692101. http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=12692101. 
6. ^ ^{a b} Grange, p. 226
7. ^ ^{a b c} American Thoracic Society, p. 370
8. ^ De Groote, MA and Huitt G. Infections due to Rapidly Growing Mycobacteria. Clinical Infectious Diseases 2006;42:1756–1763.
9. ^ ^{a b c} Grange, p. 225
10. ^ ^{a b} Grange, p. 223

References

• Griffith, David E.; Aksamit, Timothy; & A. Brown-Elliott, Barbara et al. (2007). American Thoracic Society Guidelines: Diagnosis, Treatment and Prevention of Nontuberculous Mycobacterial Diseases. Am. J. Respiratory and Critical Care Medicine, Vol. 175, pp. 367-417.

• Grange, J. M. (2007). "Environmental mycobacteria". In Greenwood, David; Slack, Richard; Peitherer, John; & Barer, Mike (Eds.), Medical Microbiology (17th ed.), pp. 221-227. Elsevier. ISBN 978-0-443-10209-7.

External links

• The NTM Handbook: A Guide for Patients with Nontuberculous Mycobacterial Infections Including MAC
• NTM Info & Research, a nonprofit research and patient support organization
• Stop NTM Now
• National Jewish Medical and Research Center
• University of Texas, Tyler Health Center
• Lung, Nontuberculous Mycobacterial Infections from eMedicine Radiology