tuberculosis in children (e)

04/08/23 1

04/08/23 2

Transmission Usually 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

04/08/23 3

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

04/08/23 4

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

Location %Lung 95.93

Intestine 1.14

Skin 0.14

Nose 0.09

Tonsil 0.09

Middle ear (Eustachian tube) 0.09

Parotid 0.05

Conjungtiva 0.05

Undetermined 2.41

04/08/23 5Figure 1. Pathogenesis of tuberculosis. PAM’S, pulmonary alveolar macrophages

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

Inhalation Alveoli Ingestion by PAM’S

Intracellular multiplicationof bacilli

Destruction of bacilli

Destruction of PAM’S

Tubercle formationResolution Hilar lymph nodes

Calcification

Secondary lung lesions

Ghon Complex Caseation Hematogenous spread

Liquefaction

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

other organs

04/08/23 6

04/08/23 7

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

04/08/23 8

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 tuberkulosis

04/08/23 9

TB classification (ATS/CDC modified)

Class Contact Infetion Diseas

e Manage

ment

0 - - - -

I + - - proph I?

II + + - proph II?

III + + + therapy

04/08/23 10

Diagnosis

1. Tuberculin skin test2. Chest X ray3. Clinical manifestation4. Microbiologic5. Pathology6. Hematological 7. Known infection source8. others : serologic, lung function,

bronchoscopy

04/08/23 11

Tuberculin test

TB infection

cellular immunity

delayed type hypersensitivity

tuberculin reaction

04/08/23 12

TUBERCULIN

StrengthTuberkulin PPD-S

mg/dosis TUTuberkulin

PPD RT 23 2 TUOT

mg/dosis Pengenceran

First 0,00002 1 - 0,011

10,000

Intermediate0,00001

- 10

5 2

5 0,1

-

11,000

12,000

Second 0,005 250 100 1,01

100

04/08/23 13

Tuberculin

StrengthPPD S

SeibertPPD RT23

first 1 TU 1 TU

intermediate(standard dose)

5-10 TU 2-5 TU

second 250 TU 100 TU

04/08/23 14

Tuberculin delivery

1. Mantoux : intradermal injection

2. Multiple puncture: • Heaf, special apparatus with 6 needles

• Tine, disposable, 4 needles

3. Patch test

04/08/23 15

Tuberculin

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

04/08/23 16

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

04/08/23 17

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

04/08/23 18

Imaging diagnostic

• routine : chest X ray

• on indication : bone, joint, abdomen

• majority of CXR non suggestive TB

• pitfall in TB diagnostic

04/08/23 19

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

04/08/23 20

Clinical manifestation

• None

• General manifestation

• Organ specific manifestation

04/08/23 21

General manifestation

• Chronic fever

• Anorexia dan BB / tidak naik

• Malnutrition

• Malaise

• Chronic cough

• Chronic / recurrent diarrhea

• Others

04/08/23 22

Gejala spesifiksesuai organ yang terkena

• Respiratorik : batuk, sesak, mengi• Nerologik : kejang, kaku kuduk• Ortopedik : gibbus, pincang• Kelenjar : membesar, skrofuloderma• Gastrointestinal : diare berlanjut• Lain-lain

04/08/23 23

Pemeriksaan mikrobiologis

• Memastikan D/ TB

• Hasil negatif tidak menyingkirkan D/ TB

• Hasil positif : 10 - 62 % (cara lama)

• Cara : – cara lama,– radiometrik, – PCR

04/08/23 24

Hematological

• Not specific

• BSR could elevate

• Limphocyte could increase

Pathology• Lymph node, hepar, pleura

• On indication

04/08/23 25

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 %

04/08/23 26

Other examinations

• Uji faal paru

• Bronkoskopi

• Bronkografi

• Serologi

• MPB64

04/08/23 27

Miller FJW. Tuberculosis in children, 1982

A minority of childrenexperience :1. Febrile illness2. Erythema Nodosum3. Phlyctenular Conjunctivitis

EVOLUTION AND TIMETABLE OF UNTREATED PRIMARY TUBERCULOSISIN CHILDREN

Complications of focus1. Effusion2. Cavitation3. Coin shadow

Complications of nodes1. Extension into bronchus2. Consolidation3. Hyperinflation

MENINGITIS OR MILIARYin 4% of children infected

under 5 years of ageLATE COMPLICATIONS

Renal & SkinMost after 5 years

1 2 3 4 5 6

BONE LESIONMost within

3 years

24 months

Resistance reduced :1. Early infection (esp. in first year)2. Malnutrition3. Repeated infections :measles, whooping coughstreptococcal infections4. Steroid therapy

infection

BRONCHIAL EROSION

Most childrenbecome tuberculin

sensitive

12 months

DIMINISHING RISK

But still possible90% in first 2 yearsGREATEST RISK OF LOCAL & DISEMINATED LESIONS

Development Of Complex

4-8 weeks 3-4 weeks fever of onset

PRIMARY COMPLEXProgressive HealingMost cases

Uncommon under 5 years of age25% of cases within 3 months75% of cases within 6 months

3-9 monthsIncidence decreasesAs age increased

04/08/23 28

Pengobatan TB

• Permulaan intensif

• Kombinasi 3 atau lebih OAT

• Teratur dan lama

• Pemberian gizi yang baik

• Pengobatan dan pencegahan penyakit lain

04/08/23 29

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, Ciprofloxacin

04/08/23 30

RIF, INH

Netral

Populasi basil TB pada pasien

Kavitas,ekstrasel

Massa kijuDalam makrofag

(intrasel)

Jumlah populasi 107 - 109 104 - 105 104 - 105

Metabolisme danperkembang biak

AktifLambat atauintermiten

Lambat

pH Netral/basa Asam

Obat paling efektif(berturut-turut)

INH, RIF,STREP

PZA, RIF, INH

04/08/23 31

Smear +Culture +

Smear -Culture +

Smear -Culture -

108

107

106

105

104

103

102

101

100

Start of treatment(isoniazid alone)

Weeks of treatment0 3 6 9 12 15 18 WHO 78351

Sensitive organisms Resistant organisms

Nu

mb

er o

f b

acil

li p

er m

l o

f sp

utu

m

Toman K. Tuberculosis. WHO, 1979

04/08/23 32

Regimen of Antituberculosis drugs

2 mo 6 mo 9 mo 12 mo

INHRIFPZA

EMBSTREP

PRED

Directly Observed Treatment Short course (DOT’S)

04/08/23 33

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

04/08/23 34

Pencegahan

• Perbaikan sosio ekonomi

• Kemoprofilaksis

• Imunisasi BCG

04/08/23 35

Kemoprofilaksis primer

• Mencegah infeksi• Anak kontak dengan pasien TB aktif, tetapi

belum terinfeksi (uji tuberkulin negatif)• Obat : INH 5 - 10 mg/kg BB/hari

04/08/23 36

Kemoprofilaksis sekunder

Mencegah penyakit TB pada anak yang terinfeksi :

1. Mantoux (+), Rö (-), klinis (-) :• Umur < 5 th• Kortikosteroid lama• Limfoma, Hodgkin, lekemi• Morbili, pertusis• Akil baliq

2. Konversi Mt (-) menjadi (+) dalam 12 bl, Rö (-), klinis (-)

Obat INH 5 - 10 mg/kg BB/hari

04/08/23 37

Imunisasi BCG

• Imunitas spesifik

• Uji tuberkulin menjadi (+)

• Mt (-) baru BCG

• Masal : langsung BCG tanpa Mt

• Reaksi lokal : membantu screening

04/08/23 38

Komplikasi tuberkulosis primer

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 limfogen4. Per kontinuitatum

04/08/23 39

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

04/08/23 40

Pleuritis TB dengan efusi

• Pleuritis TB biasanya dengan efusi• Terjadi karena :

– Perluasan fokus TB dekat pleura– Penyebaran hematogen

• Hipersensitivitas terhadap tuberkulin efusi pleura

• Pungsi pleura• Dapat berupa empyema

04/08/23 41

Akibat pembesaran kelenjar

• Menekan bronkus :– Atelektasis– Emfisema

• Menembus bronkus :– Penyebaran bronkogen– Fistula

TB Tulang dan Sendi

Spondilitis

Koksilitis

Gonitis

Daktilitis (spina ventosa)

04/08/23 42

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

04/08/23 43

TB Mata

• TB primer konjungtivapembesaran kelenjar preaurikuler

• TB koroid funduskopi• Conjunctivitis phluctenularis :

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

04/08/23 44

Mycobacterium atipic(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

04/08/23 45

DOTS with a SMILE

S : SupervisedM : MedicationI : InL : a LovingE : Environment

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

S : SupervisedM : MedicationI : InL : a LovingE : Environment

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