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 leprosy (also known as Hansen's disease). NTM do cause pulmonary diseases that resemble tuberculosis.[2] Mycobacteriosis is any of these illnesses, usually meant to exclude tuberculosis. They occur in many animals, including humans.

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:

Taxonomy

In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (Runyon classification):[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.[5]

However, even with these new techniques, the Runyon classification is still sometimes used to organize the mycobacteria into categories.[6]

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.[7] 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".[8]

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.[8]

Mayo Clinic researchers found a three-fold increased incidence of cutaneous NTM infection between 1980 to 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.[9] M. chelonae infection outbreaks, as a consequence of tattooing with infected ink, have been reported in the United Kingdom[10] and the United States.[11]

Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery) and pulmonary infections.[12]

Pathogenesis

The most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, and disseminated disease are also important.[8]

Pulmonary disease caused by NTM is most often seen in post-menopausal women. It is not uncommon for cystic fibrosis, Alpha-1 Antitrypsin Deficiency, Marfan Syndrome and Primary ciliary dyskinesia 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.[13]

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.[14]

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.[14]

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.[13]

Diagnosis

A) Neck and chest of a 53-year-old woman 14 days after fractionated CO2 laser resurfacing, showing Nontuberculous Mycobacterial infection B) Neck of the patient after 5 months of multidrug therapy and pulsed dye laser treatment.

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.[13] 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.[7]

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 conducted 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 were made by mid-2009, and the study can be found at the CDC: Nontuberculous Mycobacteria from Household Plumbing of Patients with Nontuberculous Mycobacteria Disease[15]

An epidemiology study on pulmonary NTM was conducted by National Institute of Allergy & Infectious Disease and results published in 2010. This study was funded by NTM Info & Research. The data can be found at PubMed here: "Nontuberculous Mycobacterial Lung Disease Prevalence at Four Integrated Health Care Delivery Systems"[16]

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.

Colorado State University have a massive research department dedicated solely to Mycobacteria research. It is dubbed the MRL, which stands for the Mycobacteria Research Lab.[17] The MRL, among many Mycobacteria species, studies the pathogenesis and drug resistance of NTMs. Specifically, Dr. Mary Ann DeGroote, a researcher at Colorado State University (as of September 2015) is conducting research on novel therapies for nontuberuclous (NTM) mycobacterial infections.[18]

Notes

  1. ↑ Atypical Mycobacteria at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ↑ American Thoracic Society (1997). "Diagnosis and treatment of disease caused by nontuberculous mycobacteria. This official statement of the American Thoracic Society was approved by the Board of Directors, March 1997. Medical Section of the American Lung Association". American Journal of Respiratory and Critical Care Medicine 156 (2 Pt 2): S1–25. doi:10.1164/ajrccm.156.2.atsstatement. PMID 9279284.
  3. 1 2 3 Grange, p. 221
  4. 1 2 Grange, p. 222
  5. ↑ American Thoracic Society, p.369
  6. ↑ 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.
  7. 1 2 Grange, p. 226
  8. 1 2 3 American Thoracic Society, p. 370
  9. ↑ Wentworth, A.B.; Drage L.A.; Wengenack N.L.; Wilson J.W.; Lohse C.M. (4 December 2012). "Increased Incidence of Cutaneous Nontuberculous Mycobacterial Infection, 1980 to 2009: A Population-Based Study.". Mayo Clinic Proceedings 88 (1): 38–45. doi:10.1016/j.mayocp.2012.06.029. PMID 23218797. Retrieved 13 December 2012.
  10. ↑ Sergeant, A.; Conaglen P.; Laurenson I.F.; Claxton P.; Mathers M.E.; Kavanagh G.M.; Tidman M.J. (25 July 2012). "Mycobacterium chelonae infection: a complication of tattooing.". Clinical and Experimental Dermatology 38 (2): 140–2. doi:10.1111/j.1365-2230.2012.04421.x. PMID 22831709. Retrieved 13 December 2012.
  11. ↑ Centers for Disease Control and Prevention (CDC) (24 August 2012). "Tattoo-associated nontuberculous mycobacterial skin infections--multiple states, 2011-2012.". CDC - Morbidity and Mortality Weekly Report (MMWR) 61 (33): 635–6. PMID 22914227. Retrieved 13 December 2012.
  12. ↑ De Groote, MA and Huitt G. Infections due to Rapidly Growing Mycobacteria. Clinical Infectious Diseases 2006;42:1756–1763.
  13. 1 2 3 Grange, p. 225
  14. 1 2 Grange, p. 223
  15. ↑ http://wwwnc.cdc.gov/eid/article/17/3/10-1510_article
  16. ↑ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2970866/
  17. ↑ http://mrl.colostate.edu/
  18. ↑ http://mrl.colostate.edu/faculty/

References

External links

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