TUBERKULOSIS pada ANAK

Penyakit

yang sudah sangat lama Ditemukan oleh Robert Koch thn 1882 Jumlah kasus TB meningkat di seluruh dunia TB pada anak meliputi masalah diagnosis, pengobatannya, pencegahannya, serta TB pada infeksi HIV Underdiagnosis / undertreatment overdiagnosis / overtreatment

Morbiditas dan mortalitas penyakit TB masih cukup tinggi. Tahun 1998-2002 jumlah kasus TB sebanyak 1086 anak dengan angka kematian berkisar 014,1%, terbanyak usia balita Faktor risiko infeksi TB : anak kontak TB dewasa, daerah endemis, penggunaan obat IV, kemiskinan, lingkungan tidak sehat dll

 Risiko

Penyakit TB ; anak balita, konversi tes tuberkulin dalam 1-2 tahun terakhir, malnutrisi, immunokompromais ( infeksi HIV, keganasan, transplantasi organ dll). Diabetes melitus, gagal ginjal kronik dll

 Port

dentre : paru paru 98% Percik renik (droplet) terhirup dan mencapai alveolus Mekanisme imunologis nonspesifik merupakan pertahanan awal Pada sebagian kecil kasus makrofag alveol tidak dapat menghancurkan kuman TB sehingga bereplikasi Makrofag hancur terbentuk fokus primer

 Kuman

TB menyebar melalui saluran limfe ke KGB regional terjadi inflamasi saluran limfe (limfangitis) dan kelenjar limfe (limfadenitis) Kompleks primer : fokus primer, limfangitis dan limfadenitis Masa inkubasi : waktu yang dibutuhkan kuman TB sejak masuk ke tubuh sampai terbentuk kompleks primer (2-12 minggu)

Infeksi Mycobacterium tuberculosis

Kuman mati

Fagositosis oleh makrofag alveolus paru Kuman hidup berkembang biak

Masa inkubasi 2-12 minggu

Uji tuberkulin (+)

Pembentukan fokus primer Penyebaran limfogen -hematogen

Kompleks primer
terbentuk imunitas spesifik seluler

Sakit TB
Komplikasi kompleks primer Komplikasi penyebaran hematogen/limfogen

Infeksi TB
Imunitas optimal

Meninggal

Sembuh

Reaktivasi/infeksi

Sakit TB

Inhalation

Alveoli

Ingestion by PAMS

Intracellular multiplication of bacilli Destruction of PAMS

Destruction of bacilli

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

Pathogenesis of tuberculosis. PAMS, pulmonary alveolar macrophages

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

EVOLUTION AND TIMETABLE OF UNTREATED PRIMARY TUBERCULOSIS IN CHILDREN

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

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 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

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

BONE LESION Most within 3 years

infection

4-8 weeks Development Of Complex

3-4 weeks fever of onset

12 months

24 months

DIMINISHING RISK
But still possible 90% in first 2 years

GREATEST RISK OF LOCAL & DISEMINATED LESIONS

Miller FJW. Tuberculosis in children, 1982

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

Infection
Positive tuberculin skin test reaction without clinical, radiographic, or laboratory evidence of disease

Disease Pulmonary
Primary pulmonary tuberculosis (hilar adenopathy with or without primary parenchymal disease Progressive primary pulmonary tuberculosis (pneumonia, endobronchial disease) Chronic pulmonary tuberculosis (cavitary, fibrotic, tuberculoma) Miliary tuberculosis Tuberculous pleural effusion

Extrapulmonary
Lymph nodes Brain and meninges Skeleton (bone and joint) Gastrointestinal tract, including liver, gall bladder, and pancreas Genitourinary tract, including kidneys Skin Eyes Ears and mastoids Heart Serous membranes (peritoneum, percardium) Endocrine glands (adrenal) Upper respiratory tract (tonsil, larynx, salivary glands)

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

Risk category
None Moderate High Received BCG immunization

Size of induration
> 15 mm > 10 mm > 5 mm > 15 mm

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

False-positive
Incorrect application of tuberculin Incorrect interpretation Cross-reactivity with nontuberculous mycobacteria

False-negative
Incubation period Incorrect storage and application of tuberculosis Incorrect interpretation Widespread tuberculous disease Coexistence of viral infections (measles, rubella, varicella, influenza, human immunodeficiency) Cellular immunoincompetence, including use of corticosteroids Complement depletion Fever Leukocytosis Malnutrition Sacoidosis Psoriasis Jejunoileal bypass Ultraviolet light exposure (sun, solaria) Zinc deficiency Pernicious anemia Inselman LS. Tuberculosis in children : An Update. Pediatr Pulmonol 1996; 21:101-20 Uremia

Parameter Kontak TB Uji Tuberkulin Tdk ada (-)

2 Laporan keluarga (BTA atau tdk jelas BTA (+)

(+) 10 mm atau 5 mm pada imunosupresi) BB/TB <90% BB/U < 80% Klinis Gizi Buruk atau BB/TB ,< 70% atau BB/U <60%

BB/Status Gizi

Demam tanpa sebab jelas Batuk Pembesaran KGB Kelaianan tulang, panggul, lutut Foto Thoraks Normal/tdk jelas

2 minggu = 3 minggu 1 cm jumlah .> 1 Ada

Sugestif TB

 Didiagnosis

TB bila jumlah skor 6 (maksimal 14)

Klasifikasi TB
Klas TB 0 I Kontak negatif positif Infeksi negatif negatif Diseases negatif negatif TLaksana negatif Profilkasis primer

II
III

positif
positif

positif
positif

negatif
positif

Profilaksis sekunder
Terapi (+)

6-month regimen INH + RIF + PZA daily for 2 months

For hilar adenopathy without drug resistance : use INH + RIF for 6 months 9-month regimen INH + RIF daily for 9 months

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

Tuberculosis meningitis, miliary tuberculosis, bone and joint tuberculosis, and congenital tuberculosis INH + RIF + PZA + SM daily for 2 months plus INH + RIF daily or 2 times/week with DOT for 10 months Mutiple drug-resistant tuberculosis INH + RIF + PZA + SM (or high-dose EMB) with DOT for 12-18 months HIV infection INH + RIF + PZA for 9 months May add SM or EMB for initial 2 months

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

Isoniazid-suspectible organisms INH for 9 months 10 mg/kg/day, max 300 mg/day, daily or 10 mg/kg/day, max 300 mg/day, daily 1 month plus 20-30 mg/kg/dose, max 900 mg/dose, 2 times/week with DOT for 8 months Isoniazid-resistant organisms RIF + INH for 9 months RIF 10 mg/kg/day, max 600 mg/day, daily + INH 10 mg/kg/day, max 300 mg/day, daily HIV infection INH for 12 months INH 10 mg/kg/day, max 300 mg/day, daily

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

Drugs Isoniazide * (INH) Rifampicin (RIF) Pyrazinamide (PZA) Ethambutol (EMB) Streptomycin (SM)

Daily dose (mg/Kg/day)

2 Time/week dose (mg/Kg/dose)

3 Time/week dose (mg/Kg/dose)

Adverse reactions
Hepatitis, peripheral neuritis, hypersensitivity
Gastrointestinal upset,skin reaction, hepatitis, thrombocytopenia, hepatic enzymes, inducing orange discolouration of secretions Hepatotoxicity, hyperuricaemia, arthralgia, gastrointestinal upset Optic neuritis, decreased visual acuity, decreased red-green colour discrimination, hypersensitivity, gastrointestinal upset

5-15 (300 mg) 10-15 (600 mg) 15 - 40 (2 g) 15-25 (2,5 g) 15 - 40 (1 g)

15-40 (900 mg) 10-20 (600 mg) 50-70 (4 g) 50 (2,5 g) 25-40 (1,5 g)

15-40 (900 mg) 10-20 (600 mg) 50-70 (3 g) 50 (2,5 g) 25-40 (1,5 g)

Ototoxicity nephrotoxicity

Values in parentheses are maximum doses * In combination with rifampicin, doses < 10 mg/kg/day When INH and RIF are used concurrently, the daily doses of the drugs are reduced

National Concensus of tuberculosis in children, 2001

2 bl

6 bl

9 bl

12bl

INH RIF PZA EMB STREP PRED

Directly Observed Treatment Short course (DOTS)

S M I L E

: Supervised : Medication : In : a Loving : Environment

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

A. Focus and complication

Primary complex Focus and Reg. glands

Rupture of focus intro pleura space with effusion; serous occ. purulen

Rupture of focus into bronchus cavitation

Enlarged focus sometime laminated round or coin shadow

B. Mediastinal (regional) nodes and complication

Incomplete bronchial Obstruction (Ball-valve) inflation of Middle & lower lobus

Collapsed right lower lobe after Complete bronchial obstruction Without consolidation

Collapsed after partial Consolidation segmental lesion

Erosion into bronchus, inhalarion And areas of Tub. Bronchopneumonia

Pericardial effusion post rupture of node through percardium

C. Sequelae of bronchial complication

Stricture of bronchus

Cylindrical bronchiectasis in area Of old collapse

Wedge shadow with fibrosis and bronchiectasis following contracture of segmental lesion

Linear scar of fibrosis following segmental lesion