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clinical manifestation of MOTT
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Asysyukriati R. Prawiro
Literature Review III
Sunday, April 23th 2012
PULMONOLOGY RESIDENT
FACULTY MEDICINE UNIVERSITY OF INDONESIA
Mycobacterium other than tuberculosis (MOTT)
Non tuberculous mycobacterium (NTM)
Atypical mycobacterium (AM)
Opportunistic mycobacterium
Unclassified mycobacterium
Annonymous mycobacterium
Environmental mycobacterium
All mycobacterial species other than Mycobacterium
tuberculosis complex and M. leprae
Jurnal Tuberkulosis Indonesia. 2004;1:1-52.
Am J Respir Crit Care Med. 2007;175:367-416.
Arch Pathol Lab Med. 2008;132:1333-40.
MOTT have been known since the time of
Robert Koch but historically
overshadowed by tuberculosis and dismissed
as contaminant
With advances in molecular microbiology and
knowledge
as true pathogens and important causes of
human infection
Difficult to diagnose and to treat
Am J Respir Crit Care Med. 2007;175:367-416.
Arch Pathol Lab Med. 2008;132:1333-40
Family: Mycobateriaceae
Ordo : Actynomycetales
Ubiquitous in the
environment
Can cause both
asymptomatic infection
and symptomatic disease
in humans
4 clinical syndromes
Lung disease
Lymphadenitis
Skin/soft
tissue/skeletal disease
Disseminated disease
Jurnal Tuberkulosis Indonesia. 2004;1:1-52
Am J Respir Crit Care Med. 2007;175:367-416.
Indian J Med Res. 2004;120:290-304.
Widely distributed in the environment with
high isolation rates worldwide
soil, natural water, tap water, water used in
showers, surgical solutions, food, birds
Human disease is suspected to be acquired
from environmental exposures
No evidence of animal-to-human or human-to-
human transmissions
Am J Respir Crit Care Med. 2007;175:367-416
Proc Am Thorac Soc. 2006;3:285-92
Am J Respir Crit Care Med. 2011;183:788-824.
Incidence
• Incidence rates vary from 1.0 to 1.8 cases per 100,000 persons
• Have been seen in most industrialized countries
• ↑ Cases ~ HIV
Prevalence
• There is not substantially more or better information about MOTT disease prevalence than that published in the 1997 ATS statement on MOTT
Am J Respir Crit Care Med. 2007;175:367-416
Proc Am Thorac Soc. 2006;3:285-92
Am J Respir Crit Care Med. 2011;183:788-824.
Predisposing factors Immunocompromized
Underlying pulmonary pathology
COPD
History of Tb
ILD / IPF
Silicosis
Asbestosis
Bronchiectasis
Cystic fibrosis
Cancer
The most common inf.
(pulmonary)
MAC/MAI
M. kansasii
M. abscessus
M. xenopi
M. malmoense
Jurnal Tuberkulosis Indonesia. 2004;1:1-52
Am J Respir Crit Care Med. 2007;175:367-416
Respirology. 2009;14:12-26
Another factors
Smoking (>30 pack/year)
Alcohol
Cardiovascular disease
Chronic liver disease
Pasca gastrectomi
•Medicinus. 2008;60-2.
Medicinus. 2008;60-2
ATSIdentified more than 125 MOTT species
Daley CL and Griffith DE identified more
than 140 MOTT species, at least 40 of which
are associated with lung infection
slowly growing mycobacteria (SGM) and
rapidly growing mycobacteria (RGM)
Runyon system 4 categories (description,
growth and pigment production)
Int J Tuberc Lung Dis. 2010;14:665–71.
Int J Tuberc Lung Dis. 2010;14:665–71.
Am J Respir Crit Care Med. 1997;156:1-25
Am J Respir Crit Care Med. 1997;156:1-25
Am J Respir Crit Care Med. 1997;156:1-25
Arch Pathol Lab Med. 2008;132:1333-40
A
B
C
D
•Nontuberculous mycobacteria. [cited 2010 June 24th]. Available from:URL:http://knoll.google.com/k/nontuberculous-mycobacteria#. •Nontuberculous mycobacteria. [cited 2010 June 24th]. Available from:URL:http://knoll.google.com/k/nontuberculous-mycobacteria#.
http://knoll.google.com/k/nontuberculous-mycobacteria#.
Port de entry
Abrasions in the skin (esp. M.
marinum)
Surgical incisions (esp. central
catheters)
Oropharyngeal mucosa (cervical )
Gastrointestinal
Respiratory tract
• Port de entry lymph reg
• Lung infect. ~ MTb
Host defense, mucociliary
clearence and
tracheobronchial secretion
Predisposing factors
• Granulomatous lession =
MTb
Jurnal Tuberkulosis Indonesia. 2004;1:1-52
Am J Respir Crit Care Med. 2007;175:367-416.m AAP Grand Rounds .2003;51:1-6
Still not completely understood
Pathogenesis 3 important observations (over
the past two decades)
1. HIV patientsdisseminated NTM infections typically
occurred only after the CD4 T-lymphocyte number <
50/ul
2. HIV-uninfected patient genetic syndromes of
disseminated NTM infection associated with specific
mutations in IFN γ & IL-12 synthesis and response
pathways
Am J Respir Crit Care Med. 2007;175:367-416.
(IFN-γ receptor 1 [IFNR1], IFNR2, IL-12
receptor 1 subunit [IL12R1], IL12p40, the signal
transducer and activator of transcription1
[STAT1], and the nuclear factor- essential
modulator [NEMO])
3. Association bronchiectasis, body habitus,
predominantly in postmenopausal women (e.g.,
pectus excavatum, scoliosis, mitral valve
prolapse)
Am J Respir Crit Care Med. 2007;175:367-416.
1. Pulmonary disease
2. Lymphadenitis
3. Skin/soft tissue/skeletal
4.Disseminated
4 clinical syndromes
Jurnal Tuberkulosis Indonesia. 2004;1:1-52
Am J Respir Crit Care Med. 2007;175:367-416
Respirology. 2009;14:12-26
Not specific Alike tuberculosis or underlying pulmonary
pathology
Cough sputum
Lose appétit
↓ body weight
Could be with lymphadenophati/hepatosplenomegali
Have predisposing factors
Am J Respir Crit Care Med. 2007;175:367-416.
Missouri Department of Health and Senior Services- Communicable Disease Investigation Reference Manual
Night sweat
Fatigue
Hemoptysis
1 (a) Axial and (b) coronal HRCT images
taken at presentation show a nodular and
tree-in-bud appearance peripherally in both
lungs, more marked on the right side with
underlying ground glass opacities
Axial HRCT image shows
a marked improvement
after nine weeks of
treatment
Singapore Med J 2008; 49: e47-9
Am J Clin Pathol 2001;115:755-762
The most common 1-5 years old and cervical
lymphadenitis ( head and neck)
Typically firm, non-tender, and painless, with non-
erythematous overlying skin
Non-fluctuant: lymph node suppuration and
spontaneous drainage may occur after caseation
and necrosis development
Arch Pathol Lab Med. 2008;132:1333-40
Journal of Microbiological Methods. 2008;75:1–11
Fever, weight loss, fatigue, and malaise are
usually absent or minimal.
Lymph node involvement typically occurs
between six to nine months following the initial
infection
HIV patient subclinical infection after
treatment with antiretroviral
Arch Pathol Lab Med. 2008;132:1333-40
Journal of Microbiological Methods. 2008;75:1–11
Common etiology :
MAC another cased by RGM, M. malmoense,
M. kansasii M.haemophilum, M. interjectum, M.
palustre, M. tusciae, M. heidelbergense, M.
elephantis, M. lentiflavum dan M. bohemicum
Arch Pathol Lab Med. 2008;132:1333-40
AAP Grand Rounds. 2003;51:1-6
The spectrum of STSIs is broad and ranges from
chronically draining, localized abscesses/nodules
to tenosynovitis to frank osteomyelitis.)
Typically indolent, and the clinical course variable
Predilection
direct inoculation such as penetrating trauma
or soilage of open wounds and fractures
Arch Pathol Lab Med. 2008;132:1333-40
Am J Respir Crit Care Med. 2007;175:367-416
Iatrogenically cause infections following
intravenous and peritoneal catheters, shunts,
intramuscular injections, cosmetic surgery
procedures, laser in situ keratomileusis
procedures, and postsurgical wounds
Minor cutaneous infections may resolve
spontaneously during the course of 8 to 12 mo.
More serious disease, such as osteomyelitis,
will likely progress over time
Arch Pathol Lab Med. 2008;132:1333-40
Am J Respir Crit Care Med. 2007;175:367-416
STSIs..
The most common etiology
M. fortuitum, M. abscessus or M. chelonae
Other species are associated with certain
clinical syndromes
Swimming pool granuloma/ fish tank granuloma
Mycobacterium marinum
Exposure to some type of marine environment
(eg, fish, crustaceans, fish tanks)
Presents as granulomatous lesions Arch Pathol Lab Med. 2008;132:1333-40
usually on portions of the extremities
prone to abrasions
begin as papules that then ulcerate and
scar
often localized, but some patients can
develop a nodular lymphangiitis similar to
sporotrichosis
Arch Pathol Lab Med. 2008;132:1333-40
Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths
Burulli ulcer
Mycobacterium ulcerans
Starts as a pruritic nodule that eventually
degenerates into a large
Irregular
Undermined ulcer
Chronic
Necrotic skin lesions of the extremities
In the tropics and Australia
Arch Pathol Lab Med. 2008;132:1333-40
Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths
•CD4 < 50 sel/μL
•Etiology : 95 % MAC
The most common
symptoms fevers,
night sweats, and weight
loss-- Diarrhea and
abdominal pain,
hepatoslenomegali ,
Mycobacterial spindle cell
pseudotumors syndrome
Immunosupresion
(transpl, cancer, steroid)
Infliximab & etanercept
Etiology: MAC,
M. kansasii, M. chelonae,
M. abscessus &
M. haemophilum.
Symptoms: fevers
Some spesies
subcutaneous nodul or
abses
Arch Pathol Lab Med. 2008;132:1333-40
Am J Respir Crit Care Med. 2007;175:367-416.m
H
I
V
N
o
n
H
I
V
Disseminated atypical mycobacterial tuberculosis with
generalized cutaneous lesions in a boy with acute
lymphoblastic leukemia in remission AAP Grand Rounds. 2003;51:1-6
Zahid M. Qureshi MD, Pediatric Tuberculosis Myths & Truths
Journal of Infection. 2007;55:484-7
1. MOTToportunistic in the environment
2. MOTT : All mycobacterial species other than
M. tuberculosis complex and M. leprae
3. MOTTdiseasepredisposing factors
4. Port de entry infection Abrasions in the skin,
surgical incisions, oropharyngeal mucosa,
gastrointestinal, respiratory tract and no
evidence of animal-to-human or human-to-
human transmissions.
5. Clinical manifestation 4 clinical
syndromes (pulmonary disease,
lymphadenitis, skin/soft tissue/skeletal
disease, disseminated disease)
6. The most commont manifestation is
pulmonary disease