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Transmision

Usually from adult TB patient with AFB (+) Modes of transmission : airborne : >90%, droplet nuclei 1-5 m orally : drink infected cow milk direct contact: skin wound congenital : during pregnancy, very rare

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Etiology
Mycobacterium tuberculosis Mycobacterium bovis

Characteristics : 1. acid fast 2. grows slowly 3. live in weeks in dry condition 4. sensitive to sunlight, ultraviolet light, temp > 600 C

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Location of primary focus in 2,114 cases, 1909-1928

Location
Lung Intestine Skin Nose Tonsil Middle ear (Eustachian tube) Parotid Conjungtiva Undetermined

%
95.93 1.14 0.14 0.09 0.09 0.09 0.05 0.05 2.41

Source: Adapted from Ghon and Kudlich, in Engel and Pirquet (eds.), Handbuch de Kindertuberkulose, Georg Thieme Verlag, Stuttgart, 1930, Vol 1

Inhalation
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Alveoli

Ingestion by PAMS

Intracellular multiplication of bacilli

Destruction of bacilli

Destruction of PAMS
Resolution

Tubercle formation

Hilar lymph nodes

Calcification Caseation Hematogenous spread

Ghon Complex

Liquefaction

Secondary lung lesions

Lesions in liver, spleen, kidneys, bone, brain, other organs

Figure 1. Pathogenesis of tuberculosis. PAMS, pulmonary alveolar macrophages

Inselman LS. Tuberculosis in children : An Update. Pediatr Pulmonol 1996; 21:101-20

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Prognostic factors

A. TB bacilli : virulence infection dose B. Patient : General condition age Nutritional state Dosis infeksi lain misalnya morbili Genetik Tekanan fisik dan psikis, misalnya trauma, tindakan bedah

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Classification

0. No contact, no infection (tuberculin negative) I. Contact, no infection (tuberculin negative) II. Contact, infection (tuberculin positive), no disease III. Tuberculosis (disease)

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TB classification (ATS/CDC modified)

Contact Infection Disease
Manage ment

Class

+ + +

proph I
proph II?

1 2 3

+ +

therapy

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Diagnosis
1. 2. 3. 4. 5. 6. 7. 8. Tuberculin skin test Chest X ray Clinical manifestation Microbiologic Pathology Hematological Known infection source Others : serologic, lung function, bronchoscopy

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Tuberculin test
TB infection
cellular immunity delayed type hypersensitivity tuberculin reaction

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TUBERCULIN
tuberculin PPD-S

Strength First

mg/dosis 0,00002 0,00001

TU 1 5 10 250

OT tuberculin PPD RT 23 2 TU mg/dosis dilution 2 5 100 0,01 0,1 1,0 1 10,000 1 2,000 1 1,000 1 100

Intermediate Second 0,005

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Tuberculin
PPD S Seibert 1 TU 5-10 TU 250 TU PPD RT23 1 TU 2-5 TU 100 TU

Strength first

intermediate
(standard dose)

second

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Tuberculin delivery

1. Mantoux : intradermal injection 2. Multiple puncture : Heaf, special apparatus with 6 needles Tine, disposable, 4 needles 3. Patch test

Tuberculin
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Mantoux 0.1 ml PPD intermediate strength location : volar lower arm reading time : 48-72 h post injection measurement : palpation, marked, measure report : in millimeter, even 0 mm Induration diameter : 0 - 5 mm : negative 5 - 9 mm : doubt > 10 mm : positive

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Tuberculin positive

1. TB infection : infection without disease / latent TB infection infection and disease disease, post therapy 2. BCG immunization 3. Infection of Mycobacterium atypic

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Anergi

tuberculin temporarily give false negative : Severe TB, eg miliary TB Severe malnutrition Steroid therapy for long term Certain viral infection : morbili, varicella Certain bacterial infection : typhus abdominalis, diphtery, pertussis Vaccination with live virus : morbili, polio Malignancy : Hodgkin disease, leukemia

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Imaging diagnostic
routine : chest X ray on indication : bone, joint, abdomen majority of CXR non suggestive TB pitfall in TB diagnostic

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Radiologic appearance
Lymph node enlargement Primary focus Atelectasis Cavity Tuberculoma Pneumonia Air trapping Tracheobronchitis Bronchiectasis Pleural effusion Miliary spread

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Clinical manifestation

None General manifestation Organ specific manifestation

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General manifestation

Chronic fever Anorexia dan BB / tidak naik Malnutrition Malaise Chronic cough Chronic / recurrent diarrhea Others

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Specific manifestation
according the involved organ

Respiratory : cough, dyspnea, wheezing Neurologic : convulsion, neck stiffness Orthopedic : gibbus, pincang Lymph node : enlargement, skrofuloderma Gastrointestinal : prolonged diarrhea

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Pemeriksaan mikrobiologis

Memastikan D/ TB Hasil negatif tidak menyingkirkan D/ TB Hasil positif : 10 - 62 % (cara lama) Cara : cara lama, radiometrik, PCR

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Hematological

Not specific BSR could elevate Limphocyte could increase

Pathology
Lymph node, hepar, pleura On indication

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Infection source

Known source of infection, has diagnostic value Shaw (1954), level of infectiousness :
AFB (+) : 62.5 % AFB (-), M tb (+) : 26.8 % AFB (-), M tb (-) : 17.6 %

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Other examinations

Uji faal paru Bronkoskopi Bronkografi Serologi MPB64

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Complications of focus 1. Effusion 2. Cavitation 3. Coin shadow

Complications of nodes 1. Extension into bronchus 2. Consolidation 3. Hyperinflation

EVOLUTION AND TIMETABLE OF UNTREATED PRIMARY TUBERCULOSIS IN CHILDREN MENINGITIS OR MILIARY in 4% of children infected under 5 years of age Most children become tuberculin sensitive
Uncommon under 5 years of age 25% of cases within 3 months 75% of cases within 6 months

LATE COMPLICATIONS Renal & Skin Most after 5 years BRONCHIAL EROSION 3-9 months

A minority of children experience : 1. Febrile illness 2. Erythema Nodosum 3. Phlyctenular Conjunctivitis

PRIMARY COMPLEX Progressive Healing Most cases

Incidence decreases As age increased

BONE LESION Most within 3 years

infection

4-8 weeks

3-4 weeks fever of onset

12 months

Resistance reduced : 1. Early infection (esp. in first year) 2. Malnutrition 3. Repeated infections : measles, whooping cough streptococcal infections 4. Steroid therapy

24 months

Development Of Complex GREATEST RISK OF LOCAL & DISEMINATED LESIONS

DIMINISHING RISK
But still possible 90% in first 2 years

Miller FJW. Tuberculosis in children, 1982

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Pengobatan TB

Permulaan intensif Kombinasi 3 atau lebih OAT Teratur dan lama Pemberian gizi yang baik Pengobatan dan pencegahan penyakit lain

Obat Anti Tuberkulosis (OAT)

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1. Isoniazid (INH)

: 5 - 15 mg/Kg BB/hari, max. 300 mg/hari oral 1 - 2 x / hari 2. Rifampisin : 10 - 20 mg/Kg BB/hari, max. 600 mg/hari oral 1 - 2 x / hari, perut kosong 3. Pirazinamid : 15 - 30 mg/Kg BB/hari, max. 2 gram/hari oral 1 - 2 x / hari (20 - 40 mg/Kg BB/hari) 4. Streptomisin : 20 - 40 mg /Kg BB/hari, max. 1gram/hari intramuskulus 5. Etambutol : 15 - 20 mg/Kg BB/hari, max. 1,5 gram/hari oral 1 x /hari, perut kosong 6. Lain-lain : Ethionamide, Kanamycin, Cycloserin, Ciprofloxacin

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Populasi basil TB pada pasien

Kavitas, ekstrasel Massa kiju 104 - 105 Dalam makrofag (intrasel) 104 - 105 Lambat Asam

Jumlah populasi

107 - 109 Aktif Netral/basa INH, RIF, STREP

Metabolisme dan perkembang biak

pH
Obat paling efektif (berturut-turut)

Lambat atau intermiten

Netral

RIF, INH

PZA, RIF, INH

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10

Number of bacilli per ml of sputum

107 106
Smear + Culture +

Sensitive organisms

Resistant organisms

105 104 103 102 101 Smear 100

Smear Culture +

Culture -

12

15

18

WHO 78351

Start of treatment (isoniazid alone)

Weeks of treatment
Toman K. Tuberculosis. WHO, 1979

Regimen of Antituberculosis drugs

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2 mo
INH RIF PZA EMB STREP PRED

6 mo

9 mo

12 mo

Directly Observed Treatment Short course (DOTS)

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Corticosteroid

Anti inflammation prednison : 1 - 3 mg/kg BB/hari, 3x/hari oral 2 - 4 minggu, tapering off Indications : TB milier Meningitis TB Pleuritis TB with effusion

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Pencegahan

Perbaikan sosio ekonomi Kemoprofilaksis Imunisasi BCG

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Kemoprofilaksis primer

Mencegah infeksi Anak kontak dengan pasien TB aktif, tetapi belum terinfeksi (uji tuberculin negatif) Obat : INH 5 - 10 mg/kg BB/hari

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Kemoprofilaksis sekunder

Mencegah penyakit TB pada anak yang terinfeksi : 1. Mantoux (+), R (-), klinis (-) : Umur < 5 th Kortikosteroid lama Limfoma, Hodgkin, lekemi Morbili, pertusis Akil baliq 2. Konversi Mt (-) menjadi (+) dalam 12 bl, R (-), klinis (-) Obat INH 5 - 10 mg/kg BB/hari

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Imunisasi BCG

Imunitas spesifik Uji tuberculin menjadi (+) Mt (-) baru BCG Masal : langsung BCG tanpa Mt Reaksi lokal : membantu screening

Komplikasi tuberkulosis primer

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1. Komplikasi komplex primer Fokus primer : kavitas, efusi pleura, dll Kelenjar : menekan bronkus, dll 2. Penyebaran hematogen Tuberkulosis milier Meningitis TB TB tulang dan sendi TB ginjal Lain-lain 3. Penyebaran limfogen 4. Per kontinuitatum

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Tuberkulosis milier

Penyebaran hematogen akut dan menyeluruh Dapat menjadi kronik Tanpa obat bisa fatal Lesi-lesi ke seluruh tubuh Demam, hepatomegali, splenomegali, tuberkel koroid mata Pungsi lumbal

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Pleuritis TB dengan efusi

Pleuritis TB biasanya dengan efusi Terjadi karena : Perluasan fokus TB dekat pleura Penyebaran hematogen Hipersensitivitas terhadap tuberculin pleura Pungsi pleura Dapat berupa empyema

efusi

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Akibat pembesaran kelenjar

Menekan bronkus : Atelektasis Emfisema Menembus bronkus : Penyebaran bronkogen Fistula

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TB Tulang dan Sendi

Spondilitis Koksitis Gonitis Daktilitis (Spina ventosa)

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TB kelenjar superfisial

Akibat penyebaran limfogen dan hematogen Dapat sembuh sendiri, dapat progresif Dapat merupakan bagian dari TB milier Biasanya multipel Lokasi : leher, axilla, inguinal, supraklavikuler, submandibula Abses

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TB Mata

TB primer konjungtiva pembesaran kelenjar preaurikuler TB koroid funduskopi Conjunctivitis phluctenularis :

Fenomena hipersensitivitas Sakit, sangat mengganggu Rekuren Terjadi dalam 5-15 tahun

Mycobacterium atipic
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(unclassified, anonymous, non tuberculous)

Runyon (1974) : Photochromogen

: M kansasi, M marinum, M siniae Scotochromogen : M scrofuloceum, M.szulgai, M. xenopi Nonphotochromogen: M avium, M intracellulare Rapid growers : M fortuitum, M chelonei

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DOTS with a SMILE

: : : : : Supervised Medication In a Loving Environment

S M I L E

(Grange JM, Int J Tuberc Lung Dis 1999; 3:360-362)

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Ilustrasi kasus

I, laki-laki 9 tahun, BB 22,500 kg Kontak hemoptoe (TB ?) Klinis baik, alergi (+) Mt (-), R : konsolidasi Feces : telur ascaris (+) Terapi : Antihistamin Obat cacing Ulang R : konsolidasi hilang

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Ilustrasi kasus

F, laki-laki 4 bulan, BB 7,200 kg Kontrol bayi sehat Minta BCG Mt (+) R : ada kelainan

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Ilustrasi kasus

LS, perempuan 4 8/12 tahun, BB 12,500 kg Keluhan : panas lama keringat malam lesu anorexia, BB kadang-kadang batuk bereak Sumber infeksi : hemoptoe Pemeriksaan : gizi kurang, BCG (-), Mt (+) R : kelainan minimal / normal LED : 23 mm/ 1 jam Biakan M.tb : (+)

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Ilustrasi kasus

MF, perempuan 2,5 bulan, BB 4,550 kg Keluhan : panas 1,5 bulan Batuk (-) D/ ISK Th/ ISK Diare berulang Mt (+), R : gambaran milier Urine : AFB (+)

panas terus