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 Nontuberculous Mycobacteria

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

Main differences of Atypical Mycobacteria 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 disease where as if M. tuberculosis is always considered pathogen when isolated.

Some characteristics of Atypical Mycobacteria: 

• Significant geographical variability both in prevalence and species responsible for 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
  • Wide spread 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 are 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 pigement 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

• M.kansasii causes lungs disease (resembling tuberculosis)
• Antigenically similar to tuberculsois (tuberculin test positive)
• Susceptible to standard anti-tuberculosis drugs
• Environmental habitat: Tap water
• Geographical habitat: USA (Texas)

Mycobacterium marinum

• Source: fresh and salt water
• Disease: Infects fish. Causes superficial granulomatous nodular skin disease of man at the site of trauma called fishtank granuloma also known as “aquarium granulma” and “swimming pool granuloma,“
• Treatment: Susceptible to tetracyclines, trimethoprim-sulfamethoxazole, and to the usual antituberculous drugs.

Group II (Scotochromogens)

1. M. scrofulaceum

• Natural habitat: Environmental water source; human respiratory tract.
• M. scrofulaceum causes scrofula- a 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 as M. avium-intracellularae (MAC/MAI) Complex
• Important pathogen in Immunocompromised individuals.
• Source: Ubiquitous in environment: water, soil, dust, animals and poultry
• Infection acquired by ingestion or inhalation.
• Pathogenesis not clearly understood.

Mycobacterium avium-intracellulare Complex (MAC)

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

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.

1. M. fortitum-chelonae complex

• 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,Tween 80 hydrolysis etc).
• molecular methods (e.g., DNA probes or 16S rRNA gene sequencing