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Global Indoor Health Network 

Mycobacterium

Mycobacterium
Mycobacterium belong to the family Mycobacterineae of the Actinobacteria. The genus contains pathogens known to cause serious disease in mammals including humans. 

Two of the better known diseases are tuberculosis and leprosy. 

Lesser known conditions are mycobacterium avium complex (MAC), hypersensitivity pneumonitis, ulcerated skin and muscle lesions, mycetoma, suspected causation of sarcoidosis, among others. Several of these conditions will be discussed below. 

A good review of MAC by the American Thoracic Society is published in the American Journal of Respiratory and Critical Care Medicine. Read the paper.

Mycobacterium are aerobic non-motile Gram-positive, being classified as an acid-fast Gram positive straight or slightly curved rods. 

All Mycobacterium species have a characteristic thick cell wall, which is hydrophobic and rich in mycolic acids (mycolates). 

Many species of the genus adapt very readily to growth on simple substrates, using ammonia or amino acids as a nitrogen source and glycerol as a carbon source. Optimum growth temperature ranges form 25 to over 50 °C. Thus, some are classified as thermophilic and are associated with lung disease.

Mycobacterium can produce pigments and are classified as to the types of pigments as follows:

Group I - Photochromogens: The species produce non-pigmented colonies when grown in the dark and become pigmented after exposures to light and re-incubated. Examples are M. kansasii, M. marinum and M. Simiae.

Group II: Scotochromogens: This group produces deep orange colonies when grown in either light or dark. The species include scrofulaceum, gordonae, xenopi and szulgai.

Groups III & IV: Non-Chromogens: The members of this group are non-pigmented in either dark or light growth conditions. Some may be pale yellow, buff or tan in color. Species of this group include tuberculosis, avium-intra-cellulare, bovis, ulcerans, fortuitum and chelonae .

Mycobacteria are widely spread in the eco-system, being present in water and food sources. They can even persist in chlorinated drinking water. Some species appear to be obligate intracellular parasites, such as in tuberculosis and leprosy. 

Several species have been identified in water-damaged building materials and contribute to the indoor air microbial contamination (Andersson et al, 1997; Torvinen et al 2006; Lignell et al, 2005; Rautiala et al, 2004; Pessi et al, 2002).

Pathogenicity and Literature on Diseases Caused by Mycobacterium species

Mycobacteria can colonize without overt symptoms of adverse health effects. A good example of this is M. tuberculosis. Billions of people around the world are infected with this organism but will never know, because they do not develop symptoms characteristic of tuberculosis. 

In addition, those individuals who develop the disease may be genetically pre-disposed. Mycobacteria infections are notoriously difficult to treat. Again, tuberculosis, leprosy and infections from M. ulcerans are prime examples. 

Because of their thick wall, these bacteria are resistant to antibiotics that attack the integrity of the cell walls, e.g., Penicillin. Also, the cell wall allows resistance to alkalis, acids, detergents, oxidative bursts and other chemical actions that cause disruption of the cell wall and eventual cell death. With this short background, we will now look at some of the health problems associated with Mycobacterium spp.

Mycobacterium Tuberculosis Complex: Several species are causative agents in human and animal tuberculosis. The species are: tuberculosis (human disease), bovis, africanum, canetfi, caprae, micro and pinnipea.

Mycobacterium Avium Complex (MAC): The below introduction is lifted from the American Thoracic Society Review in 2007, mentioned above. 

The NTM acronym used below refers to Non Tuberculosis Mycobacterium. 

This is the third statement in the last 15 years dedicated entirely to disease caused by WM. The current, unprecedented high level of interest in NTM disease is the result of two major recent trends: the association of NTM infection with AIDS and recognition that NTM lung disease is encountered with increasing frequency in the non-AIDS population. 

Furthermore, NTM infections are emerging in previously unrecognized settings with new clinical manifestations. 

Another major factor contributing to increased awareness of the importance of NTM as a human pathogen is improvement in methodology in the mycobacteriology laboratory, resulting in enhanced isolation and more rapid and accurate identification of NTM from clinical specimens. 

Consistent with the advances in the mycobacteriology laboratory, this statement has an emphasis on individual NTM species and the clinical disease—specific syndromes they produce. A major goal is facilitating the analysis of NTM isolates by the health care provider, including determination of the clinical and prognostic significance of NTM isolates and therapeutic options. 

There are controversies in essentially all aspects of this very broad field and, whenever possible, these controversies are highlighted. Hence, an attempt is made to provide enough information so that the clinician understands the recommendations in their appropriate context, especially those made with inadequate or imperfect supporting information. 

Also, when there is not compelling evidence for one recommendation, alternative recommendations or options are presented. 

When the last ATS statement about NW was prepared in 1997, there were approximately 50 NTM species that had been identified. Currently, more than 125 NTM species have been cataloged. 

A list of NM species identified since 1990 is provided in the online supplement. 

There has been a dramatic, recent increase not only in the total number of mycobacterial species but also in the number of clinically significant species. 

Clinicians might reasonably ask, 'Why are there so many new NTM species?" 

The increase relates to improved microbiologic techniques for isolating NTM from clinical specimens and, more importantly, to advances in molecular techniques with the development and acceptance of 165 rRNA gene sequencing as a standard for defining new species. 

PATHOGENESIS 

Over the past two decades, three important observations have been made regarding the pathogenesis of NTM infections: 

1. In patients infected with HIV, disseminated NTM infections typically occurred only after the CD4+ T-lymphocyte number had fallen below 50Ip1, suggesting that specific T-cell products or activities are required for mycobacterial resistance. 

2. h the HIV-uninfected patient group, genetic syndromes of disseminated NTM infection have been associated with specific mutations in interferon (IFN)- y and interieulcin (114-12 synthesis and response pathways (FN-y receptor 1 [FNyR1], IFN-y receptor 2 [IFNyR2], IL-12 receptor 131 subunit [11_12R1311, the 1-12 subunit p40 [IL12p40], the signal transducer and activator of transcription 1 ISTAT1], and the nuclear factor-1 essential modulator [NE MC]). 

3. There is also an association between bronchiectasis, nodular pulmonary NTM infections and a particular body habitus, predominantly in postmenopausal women (e.g., pectus excavatum, scoliosis, mitral valve prolapse). 
Mycobacterium bovis

Mycobacterium bovis


CLINICAL PRESENTATIONS AND DIAGNOSTIC CRITERIA 

Pulmonary Disease

Chronic pulmonary disease is the most common clinical manifestation of NTM. MAC, M. kansasii, and M. abscessus, in that order, were the most fre quent NTM pulmonary pathogens in the United States between 1981 and 1983. 

In that study, there was a predominance of males with NTM pulmonary disease in general and in disease caused by all species except M. chelonae (probably M. abscessus) and M. simiae. The mean age of patients with NTM pulmonary disease was 57 years. 

In the CDC report from the mid-1990s, MAC, M. kansasii, and M. fortuitum were the most frequent pulmonary pathogens in the United States between 1993 and 1996. Males predominated in disease caused by all species except M. abscessus and the majority of isolates were from patients 50 years of age or older. 

In light of more recent information that reflects a post-menopausal female patient predominance for MAC lung disease, it is likely that these epidemiologic estimates are not currently valid. 

Symptoms and signs

The symptoms of NTM pulmonary disease are variable and nonspecific. However, virtually all patients have chronic or recurring cough. Other symptoms variably include sputum production, fatigue, malaise, dyspnea, fever, hemoptysis, chest pain and weight loss. Constitutional symptoms are progressively more prevalent with advancing NTM lung disease. 

Evaluation is often complicated by symptoms caused by coexisting lung diseases, such as bronchiectasis, chronic obstructive airway disease associated with smoking, cystic fibrosis and pneumoconiosis. 

Physical findings are nonspecific and reflect underlying pulmonary pathology, such as bronchiectasis and chronic obstructive lung disease. 

On chest auscultation, findings may include bronchi, crackles, wheezes and squeaks. Patients with nodular/bronchiectatic MAC disease tend to be postmenopausal women, many of whom also have a characteristic morphotype with a thin body habitus and may also have scoliosis, pectus excavatum and mitral valve prolapse. 

Mycobacterium and Sarcoidosis 

Sarcoidosis is an inflammatory disease that can affect almost any organ in the body. It causes heightened immunity, which means that a person's immune system, which normally protects the body from infection and disease, overreacts resulting in damage to the body's own tissues. The disease is mediated by either or both Th1 and Th2 T cells. 

The classic feature of sarcoidosis is the formation of granulomas--microscopic clumps of inflammatory cells that group together (and look like granules, hence the name). When too many of these clumps form in an organ, they can interfere with how that organ functions. 

In people in the United States, sarcoidosis most commonly targets the lungs and lymph nodes, but the disease can and usually does affect others organs, too, including (but not limited to) the skin, eyes, liver, salivary glands, sinuses, kidneys, heart, the muscles and bones, and the brain and nervous system. 

Evidence from several lines indicates that Mycobacterium spp are involved in the disease process. The evidence includes: 

(1) demonstration of Mycobacterium DNA in granulomas (Drake et al, 2002; Saboor et al, 1992); 

(2) the induction of interferon gamma of patient lymphocytes by antigens of Mycobacterium (Carlisle et al, 2007; Allen et al, 2008) and 

(3) and epidemiological evidence that have an etiological role in the disease (Gupta et al, 2007). 

Finally, HLA phenotypes appear to increase the risk for developing sarcoidosis in both Caucasians and Afro-Americans (Rossman et al, 2003; 2008). 

From these data, it can be concluded that Mycobacterium spp have an etiological role in some cases of Sarcoidosis and that certain HLA phenotypes increase the risk of the disease. 

Mycobacterium and Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (also known as Hot Tub Fever or Farmer's Lung disease) is a granulomatous disease of the lungs caused by Mycobacterium avium complex. The disease is characterized by reactive airways, inflammation, nodular infiltrates (granulomas), and bronchiectasis. The intracellulare form is increasingly recognized as a pulmonary pathogen. 

For more information, see: Waller et al, 2006; Sood et al, 2006; Hanak et al, 2007; Embil et al, 1997. 

Several species of Mycobacterium avium complex have been identified in damp indoor spaces. 

Skin Lesions and Lymphoadenopathy

M. Ulcerans is endemic to the tropical regions of the world. It produces Mycolactone which is immunosuppressive and cytotoxic. 

M. marinum and liflandii have been identified as two other species that produce this toxin. These organisms are present in fresh and salt water. Ulcerans and marinum have been noted to cause skin lesions in humans that ulcerate and can cause necrosis of underlying muscle. 

Inflammation is found in the lesions that include neutrophils and lymphocytes. Usually, the lesions are not painful because mycolactone suppresses pain reception. Infections may occur in individuals who handle fish, e.g., aquarium fish or fisherman who are exposed to the organisms. 

Marinum has a worldwide distribution and has been identified off the Florida Coast, Gulf of Mexico an California Coast. These conditions are noted here since the spectrum of mycolactone producing Mycobacterium has not been completely investigated. 

For more information, see Pidot et al, 2008; Ang et al, 2000; Tran et al, 2008; Williamson et al, 2008; Simmonds et al, 2009; Sarfo et al, 2020). 
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