Atypical Mycobacterial Infections

Atypical mycobacterial infections caused by a species of mycobacterium other than M. tuberculosis complex,  the causative bacteria of pulmonary TB and extrapulmonary TB including cutaneous TB; and Mycobacterium leprae, the cause of leprosy. Atypical mycobacteria include species such as M. avium, M. intracellularae, M. kansasii, M. xenopi, and M. fortuitum. In the acquired immunodeficiency syndrome (AIDS),  Mycobacterium avium-intracellulare, Mycobacterium kansasii, and Mycobacterium xenopi have caused widely disseminated infection.

Other names used to designate Non-tuberculous mycobacteria

• MOTT (mycobacteria other than tubercle bacilli)
• Anonymous
• Atypical
• Tuberculoid
• Environmental
• Opportunistic

Differences with Mycobacterium tuberculosis

1. MOTTs infections are not spread from person to person. With the exception of organisms causing skin lesions (M. kansasii, and possibly M. simiae), there is very little evidence of person-to-person spread of these organisms.
2. Isolation of MOTTs is not equated with a disease whereas if M. tuberculosis is always considered a pathogen when isolated.

NTM lung infections occur more frequently in older adults and people with other lung diseases, like bronchiectasis and chronic obstructive pulmonary disease (COPD).

Some characteristics of Atypical Mycobacteria

• Significant geographical variability both in prevalence and species responsible for the disease.
• Location:
  • Ubiquitous in the environment
  • Colonize skin, respiratory and GI tract
• Little is known about how the infection is acquired.
  • Not usually transmitted from person to person
• Transmission via:
  • Trauma
  • Inhalation of aerosols or ingestion
  • Nosocomially or iatrogenically
• Interpretation of positive NTM culture is complicated
  • Widespread distribution in nature
  • Colonization without causing disease
• With some exceptions, little is known about the pathogenesis of infections caused by NTM
• Atypical Mycobacteria
• Incidence: MOTT is being detected more frequently:
  • better identification techniques
  • becoming more prevalent
• Clinical disease: Presentation is variable.
  • Similar to tuberculosis
  • Predominantly localized skin infection.

Runyon Classification of NTM

• A typical mycobacteria were first classified by Runyon into four groups
• Basis
  • Growth rate
  • Colonial pigmentation

Runyon proposed the following scheme:

• Group I: Photochromogens (photo means light; and chromogen means color, i.e producing color in light)
• Group II: Scotochromogens (scoto-, darkness, Greek σκότος (skotos); chromogen means color i.e. produce the pigments chiefly in dark)
• Group III: Non-chromogens (non: no; chromogen: color) These NTMs produce little or no yellow-orange pigment, irrespective of presence or absence of light
• Group I-III are slow growers: Group IV- Fast growers (3-5 day)

Note: Chromogen (a substance that can be readily converted into a dye or other colored compound.)

Group I: Photochromogens

Among the NTM classified as photochromogens, M. kansasii, M. marinum are the major potential pathogens. M. asiaticum, M. intermedium are found to be associated with pulmonary disease.

1. Mycobacterium Kansasii
   Causes chronic pulmonary disease as well as infections of the skin and subcutaneous lymph nodes.
   The disease tends to progress slowly and is susceptible to usual mycobacterial drugs.
   M.kansasii causes lungs disease (resembling tuberculosis)
   1. Antigenically similar to M. tuberculsois (tuberculin test positive)
   2. Susceptible to standard anti-tuberculosis drugs
   3. Environmental habitat: Tap water
   4. Geographical habitat: USA (Texas)
2. Mycobacterium marinum
   It grows at much lower temperatures than other mycobacteria (i.e. around 30°C) and is present in both fresh and saltwater.  It causes nodular ulcerative lesions of the skin at the site of trauma. The infection may spread to the liver through lymphatic circulation.
   1. Source: fresh and saltwater
   2. Disease: Infects fish. Causes superficial granulomatous nodular skin disease of man at the site of trauma called fishtank granuloma also known as “aquarium granuloma” and “swimming pool granuloma,“
   3. Treatment: Susceptible to tetracyclines, trimethoprim-sulfamethoxazole, and to the usual antituberculous drugs.

Group II (Scotochromogens)

M. scrofulaceum is an NTM classified as scotochromogens and is found in raw milk, soil, water, and dairy products.
It is the most common cause of granulomatous cervical lymphadenitis in children. The disease is characterized by enlarged lymph nodes, which may ulcerate or form draining sinus tracts.

• Natural habitat: environmental water source; human respiratory tract.
• M. scrofulaceum causes scrofula- granulomatous cervical adenitis in children.
• Enters through oropharynx and infects the draining lymph nodes
• Treatment: surgical excision of affected lymph nodes.

Group III (Non-chromogens)

• Includes M. avium and M. Intracellularae also referred to as M. avium-intracellularae (MAC/MAI) Complex
• The important pathogen in immunocompromised individuals.
• Source: ubiquitous in the environment: water, soil, dust, animals, and poultry
• Infection acquired by ingestion or inhalation.
• Pathogenesis not clearly understood.

Mycobacterium avium-intracellulare Complex (MAC)

These Non-Tuberculous Mycobacteria (NTM) are classified as Nonphotochromogens in Runyon classification. M. avium complex was first recognized as human pathogens in the 1990s.  They are an important pathogen in immunocompromised and immunocompetent populations.

They are ubiquitous in environmental sources including natural waters; soil etc.  Taxonomically, the M. avium-intracellularae complex comprises M. avium, M. intracellularae, M. paratuberculosis, M. lepraemurium, and the “wood pigeon” bacillus.

These organisms cause opportunistic infections in immunocompromised patients such as individuals infected with HIV. The lungs are primarily affected, but infection can spread to other organs as well. Disseminated disease is seen in the case of AIDS patients.

• Disease:
  • MAC/MAI causes opportunistic infections in immunocompromised patients g. those with AIDS who have CD4 cell count less than 200/μl
  • Pulmonary disease caused by MAC is clinically indistinguishable from pulmonary tuberculosis.
• Highly resistant to antituberculous drugs
  • As many as six drugs in combination are frequently required for adequate treatment.
  • The current drug of choice-clarithromycin plus one or more of the following: ethambutol, rifabutin, or ciprofloxacin.

Mycobacterium ulcerans

• Mycobacterium ulcerans causes Buruli ulcer: a necrotising disease (causing tissue death) of the skin and underlying tissue.

Buruli ulcer presents in two different forms

• Non-ulcerative forms are nodules, plaques and oedema.
• The ulcerative form may be small or large with the typical undermined edges

Group IV: Rapid growers

Colonies appear on solid media in 7 days or less.

Mycobacterium fortuitum complex (Rapid growers)

It is a group of free-living; rapid-growing NTM. The colonies of these organisms appear on solid media in 7 days or less. They constitute the second major group of NTM.

They have been found in soils, marshes, rivers etc. People acquire the infection when organisms gain entry into the host by inoculation into skin and subcutaneous trauma, injections, or surgery or through animal contact.

Injection site abscesses among drug users are the most common form of this disease but pulmonary infection occurs occasionally. Infection can also be associated with implanted devices.  Little is known about the pathogenesis of these organisms.

Of the potentially pathogenic, rapidly growing NTM, M. fortuitum, M. chelonae, and M. abscessus constitute approximately 97% of disease.

• Group of free living, rapid growing mycobacteria.
• Rarely cause human disease
• Common disease: injection-site abscesses among drug abusers.
• Infections has also been associated with implanted devices such as heart valves, surgery and breast abscesses.

Laboratory diagnosis of Atypical Mycobacterial diseases

Specimen: Sputum, pus, or exudate

Microscopy: Ziehl-Neelsen staining (AFB staining) of smear shows acid-fast bacilli.

Culture: Atypical mycobacteria grow well in LJ, Middlebrook, and Dubo’s media.

Differentiation from M. tuberculosis requires

• biochemical tests (Niacin, Nitrate Reduction Test, catalase test,Tween 80 hydrolysis, etc).
• molecular methods (e.g., DNA probes or 16S rRNA gene sequencing

References

1. Bhambri, S., Bhambri, A., & Del Rosso, J. Q. (2009). Atypical mycobacterial cutaneous infections. Dermatologic clinics, 27(1), 63–73. https://doi.org/10.1016/j.det.2008.07.009 
2. Greinert U. (1992). Clinical atypical mycobacterial infections. Immunitat und Infektion, 20(2), 32–35.