Diagnosis & Treatment

of Pediatric TB
Tjatur Kuat Sagoro

Persahabatan hospital
01/17/16

Dr.Tjatur Kuat Sagoro SpA

Tempat dan tanggal lahir :Semarang, 18 Oktober 1961
Pendidikan :
- FK UGM : 1987
- IKA FK UNDIP : 1998

- Fellowship Respirologi IKA FK UI

Organisasi :
- Sekretaris UKK Respirologi Cab.DKI Jakarta
- Anggota UKK Respirologi IDAI
- Anggota IDI,IDAI
- Anggota Pokja Practical Approach to Lung Health (PAL)Depkes

Tempat bekerja : RS Persahabatan Jakarta

01/17/16

Indonesia peringkat ke 3 penduduk terbanyak

penderita TB
Global TB : Insidens BTA + : 105/100.000
penduduk
Tatalaksana TB : pada penderita sakit TB
infeksi TB ?
Pendekatan pencegahan infeksi dan sakit TB

Definition
Tuberculosis is a disease due to
Mycobacterium tuberculosis
infection with systemic spread
thus can affect almost all
organs, and the most frequent
site is in the lung, which usually
as the site of primary infection

Faktor risiko
Risiko infeksi :
Terpajan orang dewasa TB aktif
Endemis,kemiskinan,lingkungan tidak sehat
Tempat penampungan umum
Risiko sakit :
Usia < 5 tahun
Konversi uji tuberkulin
Malnutrisi,imunokompromais

Risiko sakit anak yang

terinfeksi TB
Umur saat
Infeksi Primer
(tahun)

Risiko Sakit
Tidak Sakit

TB Paru

TB Diseminata
(milier,
meningitis

<1

50%

30-40%

10-20%

1-2

75-80%

10-20%

2-5%

2-5

95%

5%

0.5%

5-10

98%

2%

<0.5%

>10

80-90%

10-20%

<0.5%

Marais et.al.Int J Tuberc Lung Dis 2004;8;392

M. tuberculosis inhalation

TB
pathogenesis

phagocytosis by PAM
live bacilli
multiplies

bacilli dead

incubation period
(2-12 weeks)

primary focus formation

lymphogenic spread
hematogenic spread1)
Primary complex2)

TST (+)

Cell mediated immunity (+)

P
r
i
m
a
r
y

TB disease

TB infection

T
B

primary complex complication

hematogenic spread complication
lymphogenic complication

Optimal immunity

3)

Dead
immunity
reactivation/reinfecktion

Cured

TB disease4)

Pathogenesis
droplet nuclei
inhalation

alveoli

ingestion by PAMS

intracellular replication
of bacilli

destruction
of bacilli

destruction of PAMS
Tubercle formation

Lymphogenic spread

Hilar lymph nodes

primary focus

lymphangitis

lymphadenitis

hematogenic spread
acute hematogenic
spread

occult hematogenic
spread

disseminated primary TB

multiple organs
remote foci

primary
complex

Figure. Pathogenesis of primary tuberculosis

CMI

TB infection & TB disease

TB infection: CMI can control
infection

primary complex (+)

cell mediated immunity (+)
tuberculin sensitivity (DTH) (+)
limited amount of TB bacilli
no clinical or radiological manifestation

TB disease: CMI failed to control TB

infection
TB infection + clinical and/or
radiological manifestation

Diagnosis

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Anak orang dewasa

kecil
aspek tumbuh kembang
neonatus dapat ASI mencret
amandel besar, pada ABG hal normal

aspek penyakit: penyakit sama, gejala

beda gejala sama penyakit beda
asma: sesak, mengi; pada anak jarang
TB: batuk, keringat malam; pada anak tdk
TB dewasa menular; pada anak tdk

Diagnostic tools

01/17/16

Clinical manifestation
Tuberculin skin test
Chest X ray
Microbiology
Pathology
Hematology
Others : serologic, lung
function, bronchoscopy
15

Suspect TB clinical
manifestation

01/17/16

body weight problem

appetite problem
recurrent ARI
multiple lymph nodes
enlargement
multi L

16

Diagnostic tools
gold standard
capture the trouble maker
microbiologic examination

adult TB

pediatric TB

sputu
m

scarce
specimen

TB culture
direct AFB
01/17/16

NTP: D/ &
evaluation

Mantoux
TST
17

Tuberculin skin test

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Mantoux TST
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 of transversal diameter :
0 - 5 mm : negative
5 - 9 mm : doubt
> 10 mm : positive
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Mantoux
tuberculi
n skin
test

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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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Tuberculin negative
1. No TB infection
2. Incubation period
3. Anergy

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Anergy
Patient with primary complex do not give
reaction to TST due to supression of CMI :
Severe TB: miliary TB, TB meningitis
Severe malnutrition
Steroid, long term use
Certain viral infection: morbili, varicella
Severe bacterial infection: typhus
abdominalis, diphteria, pertussis
Viral vaccination: morbili, polio
Malignancy: Hodgkin, leukemia, ...
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Algorithm for Early Detection and Referral for

Childhood Tuberculosis in Indonesia
Suspected TB:
Close contact with adult with AFB sputum (+)
Early reaction of BCG (in 3-7 days)
Weight loss with no apparent cause, or underweight
with no improvement in 1 month with adequate
nutritional support (failure to thrive)
Prolonged/recurrent fever with no apparent cause
Cough more than 3 weeks
Specific enlargement of superficial lymph node
Scrofuloderma
Flychten conjunctivitis
Tuberculin test positive (> 10 mm)
Radiological findings suggestive TB

If > 3 positive
01/17/16

Next page
26

Considered TB
Give anti-TB therapy
Observation in 2 months
Clinical response (+)
TB
Continue anti-TB therapy

No clinical
response/worsening
Not TB

MDR TB

Refer to hospital

ATTENTION
Presence of any dangerous signs: Reevaluation in Referral Hospital:
Clinical signs
Seizure
Decreased level of consciousnessTuberculin test
Radiological findings
Neck stiffness
Microbiology and serology
Or signs such as:
examination
Spinal tumor/lump
Histopatology examination
Limping
Diagnostic procedure and therapy
Dam board phenomenon
according to each hospitals protocol
01/17/16to hospital
27
Send

UKK Pulmonologi IDAI. Jakarta;2002.

Encountered problem
Increasing demands of TB drugs
for Pediatric TB
Increasing diagnosis of Pediatric
TB using the IDAI algorhitm
Over diagnosis !?
Need improvement IDAI scoring
system
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IDAI Pediatric TB scoring

Feature
0
1
2
3
system
Contact

not
clear

reported,
AFB(-)

AFB(+
)

TST

positiv
e

BW (KMS)

<red line,
BW

severe
malnutritio
n

Fever

unexplained

Cough

<3week
s

>3weeks

Node
enlargemn
t

>1 node,
>1cm,painle
ss

Bone,joint

swelling

normal

sugestive

CXR
01/17/16

Score

29

Notes for IDAI scoring

system
Diagnosis by doctor

BW assessement at present
Fever & cough no respons to standard tx
CXR is NOT a main diagnostic tool in children
All accelerated BCG reaction should be
evaluated with scoring system
TB diagnosis total score >6
Score 4 in under5 child or strong suspicion,
refer to hospital
INH prophylaxis for AFB(+) contact with score
<5
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Masalah baru Sistem Skoring

TB :

TERLALU
diterima
Depkes
setengah hati
01/17/16

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Masalah baru Sistem

Skoring
TB
Fasilitas
Sarana OK
kesehata
n
lengkap

SDM OK
Analisis OK

TB anak
diagnosis tepat

Sistem Skoring
TB anak

Fasilitas
kesehata
n
terbatas
01/17/16

Sarana
terbatas,
SDM terbatas

TB anak
overdiagnosis
32

Sistem Skoring TB di RS

entry point
YES
end point
NO
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Skrofuloderma

Gibbus pada Spondilitis TB

TB tulang belakang, TB
lutut

Gonitis TB

Treatment

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The main problems

Diagnosis
Clinical manifestations : not specific both
over/under diagnosis & over/under
treatment
diagnostic specimen : difficult to obtain
TB infection or TB disease ? no diagnostic
tool to distinguish

Treatment
Adherence / compliance
Drug discontinuation treatment failure
Multi drug resistance (MDR)
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Pediatric TB therapy
2 mo
6 mo
9 mo
regimen

12mo

INH
RMP
PZA
ETB
SM
PREDNISON

DOTS !
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40

Drugs

Daily dose
(mg/Kg/day)

Isoniazide *
(INH)

5-15
(300 mg)

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

15-40
(900 mg)

Adverse reactions

15-40
(900 mg)

Hepatitis, peripheral neuritis,

hypersensitivity

Rifampicin
(RIF)

10-15
(600 mg)

10-20
(600 mg)

10-20
(600 mg)

Gastrointestinal upset,skin reaction,

hepatitis, thrombocytopenia,
hepatic enzymes, inducing orange
discolouration of secretions

Pyrazinamide
(PZA)

15 - 40
(2 g)

50-70
(4 g)

50-70
(3 g)

Hepatotoxicity, hyperuricaemia,
arthralgia, gastrointestinal upset

Ethambutol
(EMB)

15-25
(2,5 g)

50
(2,5 g)

50
(2,5 g)

Optic neuritis, decreased visual

acuity, decreased red-green colour
discrimination, hypersensitivity,
gastrointestinal upset

Streptomycin
(SM)

15 - 40
(1 g)

25-40
(1,5 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

Ped TB treatment
principles
Multi drug, NOT single drug
(monotherapy)
to prevent drug resistance
risk of fall and rise phenomenon
each TB drug has specific action to certain
TB bacilli population

Long term, continue, uninterrupted

problem of adherence (compliance)
The drug is taken daily and regularly
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Treatment problem
solutions
DOTS : Directly Observe
Treatment Short-course
FDC : Fixed dose combination i.e.
>2 drugs in one tablet / capsule
in a fixed dose formulation

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Program
Nasional
Penanggulangan
Tuberkulosis

dots

International Standards
for TB Care, ISTC

TB

01/17/16

45

DOTS
Pediatric TB

National TB Program
(NTP)
Adult patient focus

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TB drugs & pharmaceutical

formulation
Isoniazid (H)
Rifampicin (R)

monosubstanc
e
combi-packs

Pyrazinamide
(Z)
Ethambutol (E)

01/17/16

fixed dose
comb
47

Combipack drugs
two or more separate drugs put in one
pack

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FDC tablet formulation

WHO
H : 30 mg
R : 60 mg
Z : 150 mg

01/17/16

IDAI
H : 50 mg
R : 75 mg
Z : 150 mg

49

WHO FDC (H/R/Z:30/60/150

&

H/R:30/60)

BW
(kg)
<7
8-9
10-14
15-19
20-24
25-29
01/17/16

Intensive, 2 mo Continuation, 4 mo
(tablet)
(tablet)
1
1
1,5
1,5
2
2
3
3
4
4
5
5
50

IDAI FDC

(H/R/Z:50/75/150 &

H/R:50/75)

BW
(kg)

Intensive, 2 mo
(tablet)

Continuation, 4
mo
(tablet)

05 - 09

10 - 14

15 - 19

20 - 33

Note: BW < 5kg should be referred and need tailored dosing

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WHO vs IDAI FDC

formulation
WHO:

INH: 4-6 mg/kgBW

BW grouping: too many
not practical
hard to remember
a gap for BW 30-33 kg

IDAI
INH: 5-10 mg/kgBW
simple BW grouping
more friendly both for doctor and patient
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FDC with IDAI formulation

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TB tracking
Adult TB
patient

centrifugal

centripetal

Child TB
patient
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TB tracking (case finding)

centripetal
trace the
source
adult people
close contact
by chest X ray

01/17/16

centrifugal
trace other
victims
children
close contact
by tuberculin

55

TB classification

(ATS/CDC

modified)
Class

Contact Infection Disease Treatment

01/17/16

proph II?

therapy

proph I

56

Primary prophylaxis
to prevent TB infection in TB Class 1 person
exposure (+), infection (-) tuberculin
negative
drug: INH 5 - 10 mg/kgBW/day
as long as contact take place, the source
should be treated
at least for 3 months
repeat TST:
negative: success, stop INH
positive: fail, become TB Class 2 continue as 2 nd
proph
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Secondary prophylaxis
to prevent TB disease in TB Class 2 person
(exposure (+), infection (+), disease (-)
and person with tuberculin conversion
certain high risk population

under five, puberty

long term use of steroid
malignancy
certain infection: morbili, pertussis

drug: INH 5 - 10 mg/kgBW/day

during the higher risk of TB disease
development: 6-12 month
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DIAGNOSIS DAN TATALAKSANA NEONATUS

DARI IBU HAMIL DENGAN TB AKTIF
(BUKU AJAR RESPIROLOGI ANAK, IDAI 2008)
Ibu hamil dengan TB aktif

Evaluasi
Awal
Dosis OAT
(mg/kg BB/hari)
Profilaksis
INH : 5-10 mg/kgbb
Terapi TB
INH
Rifampisin
Pirazinamid

Partus
Neonatus
Evaluasi klinis
Foto R
Pemeriksaan klinis &
Pemeriksaan penunjang Normal

DK/Kontak TB (+)
Profilaksis primer

Klinis TB (+)
DK/TB perinatal
Terapi TB

Pemeriksaan bilas lambung

(Bila pemeriksaan penunjang > 1 (+)
Langsung terapi TB 9 bulan

Evaluasi

Tuberkulin (+)

1 bulan

DK/TB
Terapi TB 9 bl

Tuberkulin (-)

DK/Kontak TB (+)
Uji Tuberkulin
(+) bila Indurasi > 5 mm Profilaksis primer
(-) bila Indurasi <5 mm

Evaluasi
3 bulan

Tuberkulin (+)
Tuberkulin (-)
Kontak (-)

a. Bila klinis (+)

DK/TB
Terapi 9 bl

b. Bila klinis (-)

DK/Infeksi TB
Stop profilaksis
tanpa sakit
Imunisasi BCG
Profilaksis sekunder
6 bl

Uji Mantoux (+)

Indurasi > 10 mm

Lengkapi :
Foto R
Bilas lambung

Tuberkulin (-)

DK/TB
Terapi TB diteruskan

Tuberkulin (-)
DK/Bukan TB
Stop terapi TB
Imunisasi BCG

Tuberkulin (+)

DK/ TB
Terapi TB
9 bl

Buktikan D/ TB pada ibu secara klinis, radiologis, & mikrobiologis. Bila D/ TB ibu tegak, obati dengan OAT
Bayi dipisahkan sampai minimal 2 minggu pemberian OAT pada ibu, namun ASI dapat diberikan
2)
Pemeriksaan penunjang: plasenta (PA: makroskopik, mikroskopik) dan darah vena umbilikalis (mikrobiologi: BTA,
biakan TB)
3)
Klinis: prematuritas, berat lahir rendah, distress pernapasan, hepato-splenomegali, demam, letargi, toleransi
minum buruk, gagal tumbuh, distensi abdomen
4)
Imunisasi BCG sebaiknya tidak diberikan sebelum usia 3 bulan
1)

Thank
01/17/16

61

presented at
Pelatihan BP4 di RSP
7 Juli 2009

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