This document discusses various non-tuberculous mycobacteria (NTM) that can cause disease in humans. It describes how NTM infections originate from environmental sources like water and soil. Common diseases include pulmonary infection, sinusitis, lymphadenitis in children, and bacteremia in immunocompromised individuals. Specific NTM like Mycobacterium avium complex, M. kansasii, M. marinum, M. xenopi, and M. malmoense are profiled, outlining their characteristic growth patterns, typical infection sites, and treatment approaches. Laboratory diagnosis and identification methods for NTM are also reviewed.

1. The Mycobacterium avium Complex and Slowly Growing Mycobacteria
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Dr. milad shahini

2. DISEASES OF NON-TUBERCULOUS MYCOBACTERIA
The genus Mycobacterium is routinely divided into two group:
 Slowly growing mycobacteria (7 days to form colonies)
 Rapidly growing mycobacteria (3 days to form colonies)
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3. DISEASES OF NON-TUBERCULOUS MYCOBACTERIA
NTM infection is from environmental sources:
o Natural waters
o Drinking water
o Household plumbing
o Soils
 NTM are not contaminants in soils and drinking water, they grow in those
habitats.
 Human infection occurs by inhaling dusts from soils and aerosols from
water
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4. DISEASES OF NON-TUBERCULOUS MYCOBACTERIA
NTM diseases:
 Pulmonary infection
 Sinusitis and otitis media
 Nosocomial infections associated with surgical interventions
 Cervical lymphadenitis in young children (18 months to 5 years)
 Bacteremia in individuals with compromised immune systems
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5. NTM PULMONARY DISEASE
There are two clinical presentations for pulmonary NTM infection
 Disease associated with cavitary lesions
 Disease associated with bronchiectasis
• Cough
• weakness
• night sweats
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6. NTM SINUSITIS AND OTITIS MEDIA
 Recently it has been shown that cases of chronic rhinosinusitis are due to
mycobacterial infections
 Both rapidly and slowly growing Mycobacterium spp
 Rare
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7. MYCOBACTERIAL CERVICAL LYMPHADENITIS IN CHILDREN
 Mycobacterial-associated cervical lymphadenitis is exclusively caused
by M.avium.
 The majority of cases are in 18-month to 5-year-old children.
 The first sign of infection is swollen lymph nodes in the head or neck,
often limited to one side.
 Infection occurs via oral ingestion of water or soil containing M.avium.
 Surgical excision of the infected lymph node is the recommended
treatment.
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8. BACTERAEMIA IN IMMUNODEFICIENT OR IMMUNOSUPPRESSED INDIVIDUALS
 Individuals that are immunodeficient due to HIV infection are much more
susceptible to NTM infection.
 In HIV-infected individuals, M. avium (87%) is by far the predominant
pathogen.
 Infection is manifest as an M. avium bacteraemia (up to 100 000 CFU/ml)
and even higher numbers (10 000 000 CFU/g) in tissue.
 Risk factors for M. avium infection in the HIV-infected include:
o consumption of spring water
o consumption of raw fish
o showering outside the home
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9. DEVICE- AND HOSPITAL-ACQUIRED INFECTIONS
 Due to the presence of slowly growing NTM in drinking water and their relative
resistance to high temperature and disinfectants, device-associated,
pseudo-infections have been associated with NTM.
 These present as outbreaks of NTM infection associated with a medical
procedure; for example, the use of bronchoscopes or catheters.
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10. DIFFERENTIAL DIAGNOSIS OF NTM INFECTION
 One of the emerging and challenging aspects of NTM disease is to determine its
prevalence in countries with a high tuberculosis (TB) burden, such as Latin America
and India
 In such regions, the proportion of citizens with access to treated water is
increasing
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11.  In countries with a high TB burden, where treated and untreated water are
both available, pulmonary mycobacteriosis could be caused by either M.
tuberculosis or by an NTM species.
 Both fibronocular (32%) and cavitary (68%) disease were seen amongst such
patients and 33% of the patients were infected with M. kansasii, 30% with M. avium
complex, and 20% with M. abscessus and M. fortuitum
DIFFERENTIAL DIAGNOSIS OF NTM INFECTION
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12. LABORATORY DIAGNOSIS OF NTM INFECTION
 The gold standard for detection of NTM infection is culture.
o Rapidly growing mycobacterial species form colonies by 3 days on agar-
based complex media
o Slowly growing species require 7-10 days or longer on agar-based complex
media
o 16S rRNA
o rRNA internal transcribed sequence (ITS)
o Hsp65
o rpoB
 An alternative to culture is PCR-based amplification of genus- or
species specific sequences
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13. MYCOBACTERIUM AVIUM COMPLEX
The MAC currently consists of:
 four subspecies:
 Seven species:
I. Mycobacterium chimaera
II. M. colombiense
III. M. marseillense
IV. M. timonense
V. M. bouchedurhonense
VI. M. ituriense
VII. M.arosiense
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14. MYCOBACTERIUM AVIUM COMPLEX
 M. avium subsp. hominissuis, M. intracellulare and M. chimaera are the only
human pathogens.
 M. avium subspecies paratuberculosis, the causative agent of Johne’s
disease in cattle is also the aetiologic agent of Crohn’s disease in humans.
 It has been shown that, unlike M. avium, M. intracellulare is not found in drinking
water.
 Isolates from drinking water and plumbing biofilms have been shown to be
exclusively M. chimaera
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15. MYCOBACTERIUM AVIUM COMPLEX
 MAC organisms show a characteristic heterogeneous colony morphology
(Figure Small translucent (smooth transparent (SMT)) colonies usually co-
occur with glossy, whitish colonies (smooth domed (SMD)).
 SMT bacteria have greater potential for intracellular multiplication in
macrophages, have greater virulence in animal models, and are more resistant
to antibiotics than SMD bacteria
Middlebrook 7H10 agar.
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16. A variety of methods are available for identifying and fingerprinting
members of the M.avium complex:
MYCOBACTERIUM AVIUM COMPLEX
1. Typing using mycobacterial interspersed repeat unit-variable number tandem
repeat (MIRU-VNTR)
2. Pulsed-field gel electrophoresis (PFGE)
3. Repetitive sequenced-based PCR (rep-PCR)
4. Insertion sequence restriction fragment length polymorphism (IS-RFLP)
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17. MYCOBACTERIUM KANSASII
 M.kansasii forms visible niacin-negative, photochromogenic colonies on
LJ slants at 2–3 weeks After 2 weeks in ambient light, the colonies turn
bright yellow or orange.
 M.kansasii causes pulmonary disease, cutaneous infections , and
disseminated disease (bacteraemia).
 Disseminated disease is usually restricted to immunodeficient individuals
or those infected with HIV
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18. MYCOBACTERIUM MARINUM
 M.marinum is a photochromogenic species with an optimal growth
temperature of 25–35C
 It is most commonly associated with a superficial cutaneous infection
sometimes referred to as ‘swimming pool granuloma’ or ‘fish-tank
granuloma’.
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19. MYCOBACTERIUM MARINUM
 Superficial infections usually heal spontaneously, but the course is very
prolonged and associated with discomfort.
 Further extension to regional lymph nodes and systemic infection does usually not occur
because of the low temperature required for optimal growth.
 Antibiotic treatment was generally successful (87%), but in a number of cases
standard antibiotic therapy was changed to antimycobacterial therapy.
 Without prompt treatment, the superficial infection spread to deeper tissues (29%), where
chemotherapy failure was more common and surgical intervention required.
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20. MYCOBACTERIUM XENOPI
• Strains of this species require 6–8 weeks to form visible, very fine, round colonies on
primary isolation.
• M.xenopi is resistance to heat and high optimum temperature
for growth, The optimum growth temperature for the species is
45C.
• Rifamycin-containing regimens were the most successful for
treatment, while clarithromycin containing regimens were
less effective.
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21. MYCOBACTERIUM MALMOENSE
• Even amongst the slowly growing mycobacteria, M.malmoense is even slower; it
takes more than 6 weeks for colonies to form on agar-based media.
• Growth rate is improved by reducing the pH to 6 and
adding pyruvate to standard mycobacterial media.
• Infection sites include the lung, skin, lymph
nodes (cervical lymphadenitis) and bursae.
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22. MYCOBACTERIUM HAEMOPHILUM
• M.haemophilum infections may be under recognized because of the
predilection of this species for a low incubation temperature (30C) and
its unique requirement for ferric ammonium citrate or hemin for growth.
• M.haemophilum commonly presents as disseminated cutaneous,
ulcerating lesions in individuals with some form of immunodeficiency,
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