Nontuberculous mycobacteria
Encyclopedia
Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are mycobacteria which do not cause tuberculosis
or Hansen's disease
(also known as leprosy).
):
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.
However, even with these new techniques, the Runyon classification is still sometimes used to organize the mycobacteria into categories.
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.
Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery) and pulmonary infections.
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.
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.
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.
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.
. 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.
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.
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
or Hansen's disease
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
(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 tuberculosisMycobacterium tuberculosisMycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
complex which can cause tuberculosisTuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
: M. tuberculosisMycobacterium tuberculosisMycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...
, M. bovisMycobacterium bovisMycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...
, M. africanum, M. microti and M. canettiMycobacterium canettiMycobacterium canettii, a novel pathogenic taxon of the Mycobacterium tuberculosis complex , was first reported in 1969 by the French microbiologist Georges Canetti from which the organism has been named. It formed smooth and shiny colonies, which is highly exceptional for the MTBC. It was...
. - M. lepraeMycobacterium lepraeMycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...
which causes Hansen's diseaseLeprosyLeprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
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 classificationRunyon classification
The 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 in 1959....
):
- Photochromogens, which develop pigments in or after being exposed to light. Examples include M. kansasii, M. simiae and M. marinum.
- Scotochromogens, which become pigmented in darkness. Examples include M. scrofulaceumMycobacterium scrofulaceumMycobacterium scrofulaceum is a species of Mycobacterium.It is the most common cause of cervical lymphadenitis in children.It is sometimes included in the "MAIS group" with Mycobacterium avium and Mycobacterium intracellulare....
and M. szulgai. - Non-chromogens, which includes a group of prevalent opportunistic pathogens called M. avium complexMycobacterium avium complexMycobacterium avium complex is a group of genetically related bacteria belonging to the genus Mycobacterium. It includes Mycobacterium avium and Mycobacterium intracellulare....
(MAC). Other examples are M. ulcerans, M. xenopi, M. malmoense, M. terrae, M. haemophilum and M. genavense. - 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.
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.
However, even with these new techniques, 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. 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".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.
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 disease are also important.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
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
and malignant disease. It can be caused by many NTM species which depends on region, but most frequently MAC and M. kansasii.
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.
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
The Buruli ulcer is an infectious disease caused by Mycobacterium ulcerans. The genus also includes the causative agents of tuberculosis and leprosy...
(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
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 mediumLowenstein-Jensen medium
The Lowenstein–Jensen medium, more commonly known as LJ medium, is a growth medium specially used for culture of Mycobacterium, notably Mycobacterium tuberculosis....
. 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
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.aspxAn 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.
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