09-08 tb pathogenesis diagnosis, lect

8/10/2019 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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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


16/53Figure. Pathogenesis of primary tuberculosis

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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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

09-08 tb pathogenesis diagnosis, lect

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