09-08 tb pathogenesis diagnosis, lect
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Darmawan B Setyanto Respirology Division, Department of Child Health
Faculty of Medicine, University of Indonesia
Tuberculosispathogenesis & diagnosis
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Tuberculosis
The reaction of the tissues of thehuman host to the presence andmultiplication of Mycobacteriumtuberculosis or Mycobacteriumbovis
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12/22/2014 6
Pediatric TB main problemsDiagnosis
Clinical manifestations & imaging: not specific both over/under diagnosis & over/undertreatmentdiagnostic specimen : difficult to obtainTB infection or TB disease ? no diagnostic toolto distinguish
Treatment Adherence / compliance Drug discontinuation treatment failureMulti drug resistance (MDR)
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symptomatology
pathophysiology
pathology
etiology
patho-genesis
immunology
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simtomatologi
patofisiologi
patologi
etiologi
pato-genesis
imunologi
Penunjang
diagnosis
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simtomatologi
patofisiologi
patologi
etiologi
pato-genesis
imunologi
Penunjang
diagnosis
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simtomatologi
patofisiologi
patologi
etiologi
pato-genesis
imunologi
Baku emas
diagnosis
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EtiologyMycobacterium tuberculosisMycobacterium bovis
Characteristics :1. live in weeks in dry condition2. no endotoxins, no exotoxins3. hematogenic spread4. grows slowly (24-32 hr)
5. non specific clinical manifestation6. aerob, organ predilection - lung7. wide spectrum of replication: dormant
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Transmission
adult patient, active lung TBcough, sneeze, speak, singdroplet nuclei: 1-5 airborne for long periodes
inhalation, reach alveolimiddle and lower lobes
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Location of primary focusin 2,114 cases, 1909-1928
Location %Lung 95.93
Intestine 1.14Skin 0.14Nose 0.09Tonsil 0.09Middle ear (Eustachian tube) 0.09Parotid 0.05Conjunctiva 0.05
Undetermined 2.41
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lymphadenitis
lymphangitis
primary focus
TB pathogenesis
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droplet nuclei
inhalation
alveoli ingestion by PAMS
intracellular replication
of bacillidestruction
of bacillidestruction of PAMS
Tubercle formation Hilar lymph nodes
hematogenic spread
multiple organsremote foci
Lymphogenic spread
disseminated primary TB
acute hematogenicspread
occult hematogenicspread
primary focus lymphangitis lymphadenitis
primary
complex
TST
TB pathogenesis
CMI
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M. tuberculosis inhalation
phagocytosis by PAM
live bacilli
multiplies
primary focus formationlymphogenic spread
hematogenic spread 1)
Primary complex 2)Cell mediated immunity (+)TST (+)
incubation period(2-12 weeks)
Pri
mar
y
TB3)
primary complex complicationhematogenic spread complication
lymphogenic complication
TB disease
Dead
Optimal immunity
TB infection
Cured TB disease 4)
immunityreactivation/reinfection
bacilli dead
TB pathogenesis
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Incubation period
first implantation primary focus4-6 weeks (2-12 weeks) incubation periodfirst weeks: logaritmic growth, : 10 3-10 4
elicit cellular responseend of incubation period:
primary complex formationcell mediated immunitytuberculin sensitivity
PrimaryTB infection has established
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Hematogenous spread
during incubation period, before TBinfection establishment:
lymphogenic spread
hematogenic spreadhematogenic spread (HS):
occult HS
acute generalized HSprotracted HS
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Occult HS
most commonsporadic, small numberno immediate clinical manifestation
remote foci in almost every organrich vascularization: brain, liver, bones& joints, kidneyincluding: lung apex regionCMI (+): silent foci - dormant,potential for reactivation
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Acute HS
less commonlarge numberimmediate clinical manifestation:disseminated TBmilliary TB, meningitis TBtubercle in same size, special
appearance in CXR
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Primary complexend of incubation period TB infection establishmentcell mediated immunity (CMI)tuberculin sensitivity (DTH)end of hematogenic spreadend of TB bacilli proliferation
small amount, live dormant in granulomanew exogenous TB bacilli: destroyed / localized
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TB infection & TB disease
TB infection: CMI can control infectionprimary complexcell mediated immunity (CMI)tuberculin hypersensitivity (DTH)no clinical or radiological manifestation
TB disease: CMI failed to control TB infection TB infection + clinical and/or radiologicalmanifestation
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TB infection
TB CMI
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TB disease
TB
CMI
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Tuberculin skin test
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Hypersensitivity type IV
delayed type hypersensitivity (DTH)cannot transferred by serum, can be by T-cells
cellular mediatedreflects the presence of Ag-specific CD 4 T-cellsassociated with protective immunity, but not acomplete correlationthree variants of DTH:
1. contact hypersensitivity2. tuberculin type hypersensitivity3. granulomas
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Tuberculin skin test (TST)i.c. tuberculin Ag-spec Tcells IFN
macrophages
TNF & IL-1
ICAM-1 & VCAM-1
Leucocytes-receptors
recruit cells
monocytes 80-90%
endothelial cells
induces, activates produces
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Tuberculin negative
1. No TB infection!2. Anergy? 3. Incubation period??
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Mantoux TSTMantoux : intracutan injection 0.1 ml PPDlocation : volar lower armreading time : 48-72 h post injectionmeasurement : palpation, marked, measurereport : in millimeter, even 0 mm Induration diameter :
0 - 5 mm : negative5 - 9 mm : doubt> 10 mm : positive
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Mantoux
tuberculinskin test
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Tuberculin positive
1. TB infection : infection without disease / latent TB infection
infection AND diseasedisease, post therapy
2. BCG immunization
3. Infection of Mycobacterium atypic
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12/22/2014 37
Diagnostic toolsgold standard
capture the trouble maker microbiologic examination
adult TB
direct - AFBLJ - TB culture
sputum
pediatric TB
scarce specimen
NTP: D/ & evaluation
MantouxTST
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The main problems
Diagnosis especially in children Diagnosis Pitfall :
Extrapolation of adult clinical manifestations:cough as a main TB symptomOver use of non reliable diagnostic tools
Treatment especially in adult
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Pediatric TB diagnosis PITFALLS
clinical: COUGH ! extrapolation of adult clinical manifestations: coughas a main TB symptomcough is NOT a main pediatric TB symptom
supporting examination: RONTGEN !
Need a systematic and critical analysis of allthe clinical and supporting data
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100
32
0
20
40
60
80
100
Diagnosed by X-ray alone
Actual cases
Over diagnosis TB by CXR
Over-diagnosis
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Diagnostic tools
Clinical manifestationTuberculin skin testChest X ray
MicrobiologyPathologyHematologyOthers : serologic, lung function,bronchoscopy
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Suspect TB clinical manifestation
Body weight problem Appetite problemRecurrent ARIMulti L
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Clinical setting management
Suspect TB
proveTBinfection
Mantouxtest
positive negative
not TB
Seek other
etiologies
completed:Ro, labDiagnosis TB
treatment
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TB classification (ATS/CDC modified)
Class Exposure Infection Disease Management
0 - - - -
1 + - - proph I
2 + + - proph II?
3 + + + therapy
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Resume diagnosis
Aspek Spesifik Sensitif KemudahanSimtomatologi - - - ++ +
Patologi Anatomik +++ ++ - -Patologi pencitraan - - + +Imunologi tuberkulin ++ ++ +
Etiologi mikrobiologi ++++ ++ - - -
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Catatan untuk sistem skoring TBDiagnosis oleh dokterBB dinilai saat datangDemam & batuk tidak respons thd terapi bakuRontgen BUKAN alat diagnostik utamaSemua reaksi cepat BCG harus dievaluasi dengansistem skoringDidiagnosis TB bila skor total >6Skor 5 pada balita dengan kecurigaan kuat rujukke RSProfilaksis INH untuk kontak dengan BTA(+) skor
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Thank you
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Presented
Lecture materialFMUI student
CAH module26 Aug 2009
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BCG vaccination
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Figure. Pathogenesis of primary tuberculosis
BCGinjection
deltoid ingestion by Mcrp
intracellular replication
of bacillidestruction
of bacillidestruction of PAMS
tubercle formation axilla lymph nodes
hematogenic spread
multiple organsremote foci
lymphogenic spread
disseminated primary TB
acute hematogenicspread
occult hematogenicspread
primary focus lymphangitis lymphadenitis
primary
complexTST
BCG vaccination
CMI
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Primary & post primary TB
Primary TB :first infectionusually in children
hematogenic spreadprimary complextuberculin sensitivity (DTH) & CMI
infection only (class 2) or disease (class 3)Post primary TB:
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Primary & post primary TB
Primary TB : Post primary TB:
usually in adults
no hematogenic spreadprimary complex & CMI already existtwo models:
1. reinfection (new, secondary, exogenous)2. reactivation of remote foci
(endogenous), as results of occult HS
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