Tuberculosis in Children (E)

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12/04/10

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

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EtiologyMycobacterium 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 C12/04/10 3

Location of primary focus in 2,114 cases, 1909-1928Location %Lung 95.93 Intestine 1.14 Skin 0.14 Nose 0.09 Tonsil 0.09 Middle ear (Eustachian tube) Parotid 0.05 Conjungtiva 0.05 Undetermined 2.4112/04/10

0.09

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Inhalation

Alveoli

Ingestion by PAMS

Intracellular multiplication of bacilli

Destruction of bacilli

Destruction of PAMSResolution

Tubercle formation

Hilar lymph nodes

Calcification Caseation Hematogenous spread

Ghon Complex

Liquefaction Lesions in liver, spleen, kidneys, bone, brain, other organs 5

Secondary lung lesions

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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 factorsA. TB bacilli : 12/04/10

virulence infection dose General condition age Nutritional state Dosis infeksi lain misalnya morbili Genetik Tekanan fisik dan psikis, misalnya trauma, tindakan bedah

A. Patient :

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Klasifikasi dasar0. Tidak ada kontak, tidak ada infeksi (uji tuberkulin negatif) I. Ada kontak, tidak ada infeksi (uji tuberkulin negatif) II. Ada infeksi, tidak ada penyakit TB (uji tuberkulin positif) III. Penyakit tuberkulosis12/04/10 8

TB classification (ATS/CDC modified)Class Contact Infetion Disease Manage ment

0 I II III12/04/10

+ + +

+ +

+

proph I? proph II? therapy9

Diagnosis1. 2. 3. 4. 5. 6. 7. 8.12/04/10

Tuberculin skin test Chest X ray Clinical manifestation Microbiologic Pathology Hematological Known infection source others : serologic, lung function, bronchoscopy10

Tuberculin testTB infection cellular immunity delayed type hypersensitivity tuberculin reaction12/04/10 11

TUBERCULINStrength FirstTuberkulin PPD-S

mg/dosis 0,00002 0,00001

TU 1 5 10 250

OT Tuberkulin PPD RT 23 2 TU mg/dosis Pengenceran 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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TuberculinStrength first intermediate(standard dose)

PPD S Seibert 1 TU 5-10 TU 250 TU

PPD RT23 1 TU 2-5 TU 100 TU

second

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Tuberculin delivery1. Mantoux : intradermal injection 2. Multiple puncture : Heaf, special apparatus with 6 needles Tine, disposable, 4 needles

3. Patch test12/04/10 14

TuberculinMantoux 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 : positive12/04/10 15

Tuberculin positive1. 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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AnergiUji tuberkulin dapat negatif untuk sementara karena : TB berat misalnya TB milier PEM berat Mendapat kortikosteroid lama Penyakit virus : morbili, varicella Penyakit bakteri : typhus abdominalis, difteri, pertusis Vaksinasi virus : morbili, polio Penyakit keganasan : penyakit Hodgkin

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Imaging diagnostic routine : chest X ray on indication : bone, joint, abdomen majority of CXR non suggestive TB pitfall in TB diagnostic12/04/10 18

Gambaran radiologi paru Pembesaran kelenjar Fokus primer Atelektasis Kavitas Tuberkuloma Pneumonia Air trapping Trakeobronkitis Bronkiektasis Efusi pleura Gambara milier

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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 Others21

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Gejala spesifiksesuai organ yang terkena Respiratorik : batuk, sesak, mengi Nerologik : kejang, kaku kuduk Ortopedik : gibbus, pincang Kelenjar : membesar, skrofuloderma Gastrointestinal : diare berlanjut Lain-lain

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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, PCR12/04/10 23

Hematological Not specific BSR could elevate Limphocyte could increase

Pathology Lymph node, hepar, pleura On indication12/04/10 24

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 EVOLUTION AND TIMETABLE OF UNTREATED PRIMARY TUBERCULOSIS IN CHILDREN

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

MENINGITIS OR MILIARY in 4% of children infected under 5 years of age Most children become tuberculin sensitiveUncommon 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

1

2

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

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BONE LESION Most within 3 years

5

6

infection

4-8 weeks

3-4 weeks fever of onset

12 months

24 months

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Development Of Complex GREATEST RISK OF LOCAL & DISEMINATED LESIONS

DIMINISHING RISKBut still possible 90% in first 2 years

27 Miller FJW. Tuberculosis in children, 1982

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

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Obat Anti Tuberkulosis (OAT)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, Ciprofloxacin12/04/10 29

Populasi basil TB pada pasienKavitas, ekstrasel Jumlah populasi Metabolisme dan perkembang biak pHObat paling efektif (berturut-turut)

Massa kiju 104 - 105 Lambat atau intermiten Netral RIF, INH

Dalam makrofag (intrasel) 104 - 105 Lambat Asam PZA, RIF, INH

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

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108

Number of bacilli per ml of sputum

107 106 105 104 103 102 101 Smear 10012/04/10 Culture -

Sensitive organisms

Resistant organisms

Smear + Culture +

Smear Culture +

0

3

6

9

12

15

18

WHO 78351

Start of treatment (isoniazid alone)

Weeks of treatment

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Toman K. Tuberculosis. WHO, 1979

Regimen of Antituberculosis drugs2 mo 6 mo 9 mo 12 mo

INH RIF PZA

EMB STREP

PRED

Directly Observed Treatment Short course (DOTS)12/04/10 32

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 tuberkulin negatif) Obat : INH 5 - 10 mg/kg BB/hari

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Kemoprofilaksis sekunderMencegah 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 12/04/10 36

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

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Komplikasi tuberkulosis primer1. 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-lain38

3. Penyebaran limfogen 12/04/10 4. Per kontinuitatum

Tuberkulosis milier Penyebaran hematogen akut dan menyeluruh Dapat menjadi kronik Tanpa obat bisa fatal Lesi-lesi ke seluruh tu

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