Nontuberculous mycobacteria

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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/Hansen's disease. NTM are able to 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 and are commonly found in soil and water. [3]

Contents

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:

Taxonomy

In 1959, botanist Ernest Runyon put these human disease-associated bacteria into four groups (Runyon classification): [4]

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. [6]

Even with these new techniques, though, the Runyon classification is still sometimes used to organize the mycobacteria into categories. [7]

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. [8] 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. [9]

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.[ citation needed ] 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 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. [10]

Mayo Clinic 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. [11] M. chelonae infection outbreaks, as a consequence of tattooing with infected ink, have been reported in the United Kingdom [12] and the United States. [13]

Rapidly growing NTMs are implicated in catheter infections, post-LASIK, skin and soft tissue (especially post-cosmetic surgery) and pulmonary infections. [14]

Pathogenesis

The most common clinical manifestation of NTM disease is lung disease, but lymphatic, skin/soft tissue, and disseminated diseases are also important. [10]

Pulmonary disease caused by NTM is most often seen in postmenopausal women and patients with underlying lung disease such as cystic fibrosis, bronchiectasis, and prior tuberculosis. It is not uncommon for 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. [15]

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. [16] 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. [17]

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. [17]

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. [15]

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 five months of multidrug therapy and pulsed dye laser treatment. Nontuberculous Mycobacterial Infection on neck and chest.jpg
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 five 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. [15] 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. [8]

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.

Related Research Articles

<span class="mw-page-title-main">Tuberculosis</span> Infectious disease

Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, 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, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. Infection of other organs can cause a wide range of symptoms.

<span class="mw-page-title-main">Bronchiectasis</span> Disease of the lungs

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 pain. Wheezing and nail clubbing may also occur. Those with the disease often get lung infections.

<span class="mw-page-title-main">Mycobacterial cervical lymphadenitis</span> Human medical condition

The disease mycobacterial cervical lymphadenitis, also known as scrofula and historically as king's evil, involves a lymphadenitis of the cervical lymph nodes associated with tuberculosis as well as nontuberculous (atypical) mycobacteria.

<i>Mycobacterium</i> Genus of bacteria

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 and leprosy in humans. The Greek prefix myco- means 'fungus', alluding to this genus' mold-like colony surfaces. Since this genus has cell walls with a waxy lipid-rich outer layer that contains high concentrations of mycolic acid, acid-fast staining is used to emphasize their resistance to acids, compared to other cell types.

<span class="mw-page-title-main">Granuloma</span> Aggregation of macrophages in response to chronic inflammation

A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious organisms including bacteria and fungi, as well as other materials such as foreign objects, keratin, and suture fragments.

<span class="mw-page-title-main">Tuberculosis diagnosis</span>

Tuberculosis is diagnosed by finding Mycobacterium tuberculosis bacteria in a clinical specimen taken from the patient. While other investigations may strongly suggest tuberculosis as the diagnosis, they cannot confirm it.

<i>Mycobacterium avium-intracellulare</i> infection Medical condition

Mycobacterium avium-intracellulare infection (MAI) is an atypical mycobacterial infection, i.e. one with nontuberculous mycobacteria or NTM, caused by Mycobacterium avium complex (MAC), which is made of two Mycobacterium species, M. avium and M. intracellulare. This infection causes respiratory illness in birds, pigs, and humans, especially in immunocompromised people. In the later stages of AIDS, it can be very severe. It usually first presents as a persistent cough. It is typically treated with a series of three antibiotics for a period of at least six months.

<span class="mw-page-title-main">Mycobacteriophage</span> Virus infecting mycobacteria

A mycobacteriophage is a member of a group of bacteriophages known to have mycobacteria as host bacterial species. While originally isolated from the bacterial species Mycobacterium smegmatis and Mycobacterium tuberculosis, the causative agent of tuberculosis, more than 4,200 mycobacteriophage have since been isolated from various environmental and clinical sources. 2,042 have been completely sequenced. Mycobacteriophages have served as examples of viral lysogeny and of the divergent morphology and genetic arrangement characteristic of many phage types.

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.

Lipoarabinomannan, also called LAM, is a glycolipid, and a virulence factor associated with Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. Its primary function is to inactivate macrophages and scavenge oxidative radicals.

<i>Mycobacteroides abscessus</i> Species of bacterium

Mycobacteroides abscessus is a species of rapidly growing, multidrug-resistant, nontuberculous mycobacteria (NTM) that is a common soil and water contaminant. Although M. abscessus most commonly causes chronic lung infection and skin and soft tissue infection (SSTI), it can also cause infection in almost all human organs, mostly in patients with suppressed immune systems. Amongst NTM species responsible for disease, infection caused by M. abscessus complex are more difficult to treat due to antimicrobial drug resistance.

<i>Mycobacterium fortuitum</i> Species of bacterium

Mycobacterium fortuitum is a nontuberculous species of the phylum Actinomycetota, belonging to the genus Mycobacterium.

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 nontuberculous mycobacteria. These bacteria cause Mycobacterium avium-intracellulare infections or Mycobacterium avium complex infections in humans. These bacteria are common and are found in fresh and salt water, in household dust and in soil. MAC bacteria usually cause infection in those who are immunocompromised or those with severe lung disease.

<i>Mycobacterium kansasii</i> Species of bacterium

Mycobacterium kansasii is a bacterium in the Mycobacterium genus. It is an environmental bacteria that causes opportunistic infections in humans, and is one of the leading mycobacterial causes of human disease after tuberculosis and leprosy.

Interferon-gamma release assays (IGRAs) are diagnostic tools for latent tuberculosis infection (LTBI). They are surrogate markers of Mycobacterium tuberculosis infection and indicate a cellular immune response to M. tuberculosis if the latter is present.

T-SPOT.TB is a type of ELISpot assay used for tuberculosis diagnosis, which belongs to the group of interferon gamma release assays. The test is manufactured by Oxford Immunotec in the UK. It is available in most European countries, the United States as well as various other countries. It was developed by researchers at the University of Oxford in England.

Mycobacterium scrofulaceum is a species of Mycobacterium.

<span class="mw-page-title-main">Chronic pulmonary aspergillosis</span> Fungal infection

Chronic pulmonary aspergillosis is a long-term fungal infection caused by members of the genus Aspergillus—most commonly Aspergillusfumigatus. The term describes several disease presentations with considerable overlap, ranging from an aspergilloma—a clump of Aspergillus mold in the lungs—through to a subacute, invasive form known as chronic necrotizing pulmonary aspergillosis which affects people whose immune system is weakened. Many people affected by chronic pulmonary aspergillosis have an underlying lung disease, most commonly tuberculosis, allergic bronchopulmonary aspergillosis, asthma, or lung cancer.

<span class="mw-page-title-main">Lung cavity</span> Medical condition

A lung cavity or pulmonary cavity is an abnormal, thick-walled, air-filled space within the lung. Cavities in the lung can be caused by infections, cancer, autoimmune conditions, trauma, congenital defects, or pulmonary embolism. The most common cause of a single lung cavity is lung cancer. Bacterial, mycobacterial, and fungal infections are common causes of lung cavities. Globally, tuberculosis is likely the most common infectious cause of lung cavities. Less commonly, parasitic infections can cause cavities. Viral infections almost never cause cavities. The terms cavity and cyst are frequently used interchangeably; however, a cavity is thick walled, while a cyst is thin walled. The distinction is important because cystic lesions are unlikely to be cancer, while cavitary lesions are often caused by cancer.

<i>Mycobacterium ulcerans</i> Species of bacterium

Mycobacterium ulcerans is a species of bacteria found in various aquatic environments. The bacteria can infect humans and some other animals, causing persistent open wounds called Buruli ulcer. M. ulcerans is closely related to Mycobacterium marinum, from which it evolved around one million years ago, and more distantly to the mycobacteria which cause tuberculosis and leprosy.

References

  1. ↑ Nontuberculous Mycobacteria at the U.S. 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. ↑ Foote, Sydney L.; Lipner, Ettie M.; Prevots, D. Rebecca; Ricotta, Emily E. (2021). "Environmental predictors of pulmonary nontuberculous mycobacteria (NTM) sputum positivity among persons with cystic fibrosis in the state of Florida". PLOS ONE. 16 (12): e0259964. Bibcode:2021PLoSO..1659964F. doi: 10.1371/journal.pone.0259964 . PMC   8659685 . PMID   34882686.
  4. 1 2 3 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, p. 221
  5. 1 2 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., p. 222
  6. ↑ American Thoracic Society, p.369
  7. ↑ 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.
  8. 1 2 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.p. 226"
  9. ↑ Bryant, Josephine M; Grogono, Dorothy M; Greaves, Daniel; Foweraker, Juliet; Roddick, Iain; Inns, Thomas; Reacher, Mark; Haworth, Charles S; Curran, Martin D (May 2013). "Whole-genome sequencing to identify transmission of Mycobacterium abscessus between patients with cystic fibrosis: a retrospective cohort study". The Lancet. 381 (9877): 1551–1560. doi:10.1016/s0140-6736(13)60632-7. ISSN   0140-6736. PMC   3664974 . PMID   23541540.
  10. 1 2 American Thoracic Society, p. 370
  11. ↑ 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. PMC   3690780 . PMID   23218797.
  12. ↑ 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. S2CID   205280965.
  13. ↑ Centers for Disease Control and Prevention (CDC) (24 August 2012). "Tattoo-associated nontuberculous mycobacterial skin infections--multiple states, 2011-2012". MMWR. Morbidity and Mortality Weekly Report. 61 (33): 635–6. PMID   22914227.
  14. ↑ De Groote, M. A.; Huitt, G. (2006-06-15). "Infections Due to Rapidly Growing Mycobacteria". Clinical Infectious Diseases. 42 (12): 1756–1763. doi: 10.1086/504381 . PMID   16705584.
  15. 1 2 3 Grange, p. 225
  16. ↑ Johnson, Margaret M.; Odell, John A. (March 2014). "Nontuberculous mycobacterial pulmonary infections". Journal of Thoracic Disease. 6 (3): 210–220. doi:10.3978/j.issn.2072-1439.2013.12.24. PMC   3949190 . PMID   24624285.
  17. 1 2 Grange, p. 223

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