TUBERKULOSIS

PADA

ANAK

Definisi
Tuberkulosis: suatu penyakit infeksi oleh
Mycobacterium tuberculosis dengan penyebaran sistemik yang mencakup hampir
seluruh organ, terutama paru sebagai
tempat infeksi primer.

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

Sejarah
ancient Egypt : gibbus
1882, Koch, identification
management : sanatorium, collapse
treatment
Chemotherapy :

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PAS 1943 Lehmann

Streptomycine 1945 - Waksman & Schats
Isoniazid 1952 Domagk
Rifampicine - 1957
5

24 Maret 1882 Robert Koch mengidentifikasi

kuman tuberkulosis

Epidemiologi
WHO : 2 miliar orang terinfeksi oleh
M.tuberculosis ( Afrika, Asia, Amerika Latin)
Masalah negara berkembang, juga negara
maju. Sejak 1990 > : strategi pengendalian,
infeksi HIV, pertumbuhan populasi cepat.
Negara berkembang : TB anak <15 th 15%,
negara maju : 5 7%

Epidemiologi . . .
Indonesia : 1994 kasus baru TB 0,4 juta
( 10% < 15 tahun). Th.1999 TB baru
583.000, kematian 140.000 orang/tahun.
Th 1998 2002 di tujuh RS Pendidikan di
Indonesia terdapat 1086 kasus TB anak,
kematian antara 0% - 14,1%. Kelompok
terbanyak usia 12 60 bulan (42,9%), untuk
bayi < 12 bulan didapatkan 16,5%.

Permasalahan khusus tuberkulosis anak

Diagnosis : sulit memperoleh spesimen diagnostik, jarang ditemukan kuman pd sediaan langsung /
kultur.
Pengobatan : sering drop out
Pencegahan : kontak, gizi, imunisasi
Infeksi HIV : dari orang-tua
Klinis /gejala : sering tidak khas
Program TB Nasional utk.dewasa : anak <

Permasalahan . . .
Underdiagnosis/overdiagnosis :
undertreatment/overtreatment
Pada anak >TB primer
Kurang membahayakan /tidak begitu
menular. Membahayakan bagi anak
sendiri : TB ekstratorakal ( meningitis,
tulang )

Etiologi . . .
Mycobacterium tuberculosis
Mycobacterium bovis
features:
slender, often slightly curved, rods
aerobic, non-motile, non-spore forming
acid fail to wash the stain out acid fast bacilli
Mycobacteria : found in environments, some strictly
human pathogen (M tb, bovis), others animal
pathogen and opportunistic pathogens in human
(atypical mycobacteria)
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TB
bacilli

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Mycobacterium tuberculosis
Unique characteristics :
1. live in weeks in dry condition
2. no endotoxins, no exotoxins
3. hematogenic spread
4. grows slowly (24-32 hr)
5. non specific clinical manifestation
6. aerob, organ predilection - lung
7. wide spectrum of replication: dormant
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Etiologi . . .
Agen tuberkulosis :
Mycobacterium tuberculosis,
Mycobacterium bovis,
M. africanum, M.avium .
Merupakan ordo Actinomisetales dan famili
Mikobacteriaseae.
Basili tuberkel, batang lengkung,Gram (+) lemah,
pleiomorfik, tidak bergerak, tidak membentuk
spora, panjang 2-4 um, berkelompok/sendiri, aerob
obligat, tahan asam , tumbuh baik 37-41 der.C

pidem iology 2

Etiologi . . .
M. tuberculosis is a non-motile, rod-shaped bacterium
measuring 2-4 x 0.2-0.5 m. It is an obligate aerobe,
which explains why it tends to be found in the wellaerated, upper lobes of the lungs.
It is a slow growing organism (dividing only every
16-20 hours) that lives within tissue macrophages.
Humans are the only reservoir of M. tuberculosis.
Both cows and humans serve as reservoirs for M.
bovis.
The organism does not have the characteristics of
either Gram positive or negative bacteria. It has a
peculiar cell wall that consists of peptidoglycan and
complex lipids. Once stained (e.g. with carbol
fuchsin), the organism will retain dyes when treated
by acidified organic compounds. Therefore, it is
classified as an acidfast bacterium.
The Ziehl-Neelsen stain is used to demonstrate the
presence of the bacilli in a smear. They appear as
bright red rods against a contrasting background.

M. tuberculosis appearing as bright

red bacilli (rods) in a sputum smear
stained with the Ziehl-Neelsen stain

demiology 3

Etiologi . . .
The cell wall is a major factor in the
virulence of the organism. It resists
destruction by many antibiotics,
acids, alkalis, osmotic lysis and
oxidation and enables the organism to
survive inside macrophages.
M. tuberculosis grows in Lowenstein
Jensen medium, an egg-based
medium, which contains inhibitors to
keep contaminants from outgrowing
the organism. Because of its slow
growth, it takes 4-6 weeks before
small buff-coloured colonies are
visible on the medium.

Typical small, buff coloured colonies of M.

tuberculosis on Lowenstein Jensen medium

Etiologi . . . .
(Sel kuman tbc dan koloni )

Penularan
Lewat udara/droplet,
dapat
juga (jarang) mel.kontak langsung
kulit/luka/lecet,
dan
(kongenital),
minum
susu terkontaminasi basil (M.bovis).
Basil tetap hidup dan virulen dlm keadaan
kering bbrp minggu, mati dlm cairan 60.C 1520 menit.
Basil tidak membentuk toksin.

Penularan . . .
Umumnya dari TB dewasa dengan BTA (+)
Cara penularan :
airborne
: >90%, droplet nuclei 1-5
orally
: drink infected cow milk
direct contact : skin wound
congenital : during pregnancy, very rare

Transm ission 1

Penularan . . .
Nearly all TB infection is acquired by inhalation of respiratory
droplets from an infectious contact.
Air droplets 3-5 m diameter
coughed, sneezed or spat out by
an open case of TB. The
droplets are inhaled by a close
contact. This may lead to a lung
infection which then may go on to
develop into disease in the lungs
and/or in other organs.

NB. Abdominal TB can also result from drinking unpasteurised cows milk infected with M.
bovis.

Penularan . . .

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Penularan . . . ( faktor yg berpengaruh)

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doses / numbers
concentration in the air
virulence
exposure duration
host immune state
22

Penularan . (tingkat transmisi) (Shaw

54)
adult
TB patient

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AFB(+)

AFB(-)
culture(+)

culture(-)
CXR (+)

65%

26%

17%
23

Patogenesis (1)
M.tbc udara fokus primer di paru
(susceptible) di alveolus fagositosis oleh
makrofagkembang biak/menghancurkan
makrofageksudasi konsolidasituberkel
Fokus primerkel.limfe hiluslimfadenitis/
limfangitismembentuk kompleks primer
K.primerpeny.organ tsb atau menetap nonaktifdpt.aktif bertahun-tahun kmd. -

Pathogenesis of tuberculosis
Inhalation of droplet nuclei
(2)
containing M.tb

No infection

Droplets > 10
intact mucosa and
upper airway

Droplet < 5
penetrate mucociliary
blanket

Transient alveolar nonspecific

inflammatory response

Organism replicates with normal

phagocytes (macrophages)

Organism spread by lymphatics locally

Organism spread by blood to other sites and lung
5%

3-10 weeks
95%

Development of specific
T-cell response

Failure adequate cellular

immune response

Macrophages are activated

and kill or retard tubercle bacilli

Disease inactive
Small number of viable
bacilli may persist

Active infection = disease

(primary lung : 3 week;
disseminated or progressive
pulmonary; months to years)
reactivation

5%

Secondary failure to maintain

adequate cellular immunity

Jacob RF, et al. Tuberculosis. Pediatr Respir Dis. 1984

Inhalation

Ingestion by PAMS

Alveoli

Intracellular multiplication
of bacilli

Destruction of bacilli

Destruction of PAMS

Resolution

Tubercle formation

Hilar lymph nodes

Calcification

Ghon Complex

Caseation

Hematogenous spread

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

Cell mediated immunity

CD4+ T-lymphocytes proliferation

Delayed-type
hypersensitivity
Promoted activity of cytotoxic CD4+ &
CD8+ T- lymphocytes & Killer cells

Th1 T-lymphocytes

Th2 T-lymphocytes

Activate
macrophages

Augment humoral
antibody synthesis

Produce cytokines
(TNF a, IFN g)
Attract & activate bloodborne monocytes

Granuloma
formation

Destroys local nonactivated macrophages

with M.tb & surrounding
tissue

Caseation
necrosis, tissue
damage,
dormancy of M.tb

Produce lysosomal
enzymes oxygen
radicals, nitrogen
intermediates, IL-2

Cavity formation
& spread of M.tb

Kill M.tb

Cell mediated immunity and delayed-type hypersensitivity in tuberculosis; M.tb, mycobacterium tuberculosis,
TNF-, tumor necrosis factor-alpha; IFN-; gamma interferon; IL-2, interleukin-2

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

droplet nuclei
inhalation

alveoli

ingestion by PAMS

intracellular replication
of bacilli

destruction
of bacilli

destruction of PAMS
Tubercle formation

Lymphogenic spread

Hilar lymph nodes

Fokus primer

lymphangitis

lymphadenitis

hematogenic spread
acute hematogenic
spread

occult hematogenic
spread

disseminated primary TB

multiple organs
remote foci

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Kompleks
primer

Figure. Pathogenesis of primary tuberculosis

CMI
30

Patogenesis . . .
lymphadenitis

lymphangitis

Fokus primer

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Kompleks primer

31

 Ghon Complex

Primary Complex

Kompleks primer

end of incubation period

TB infection establishment
tuberculin sensitivity (DTH)
cell mediated immunity
end of hematogenic spread
end of TB bacilli proliferation
small amount, live dormant in granuloma
new exogenous TB bacilli: destroyed / localized

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Patogenesis (3)

Patogenesis (4)

Masa inkubasi
first implantation primary complex
4-6 weeks (2-12 weeks) incubation period
first weeks: logaritmic growth, : 103-104 elicit
cellular response
end of incubation period:
primary complex formation
cell mediated immunity
tuberculin sensitivity

PrimaryTB infection has established

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Penyebaran hematogen
during incubation period, before TB
infection establishment:
lymphogenic spread
hematogenic spread

hematogenic spread (HS):

occult HS
acute generalized HS
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Penyebaran hematogen .occult

/tersembunyi

most common
sporadic, small number
no immediate clinical manifestation
remote foci in almost every organ
rich vascularization: brain, liver, bones &
joints, kidney
including: lung apex region
CMI (+): silent foci - dormant, potential
for reactivation
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Penyebaran hematogen . . .

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Penyebaran hematogen .acute

generalized/nyata
less common
large number
immediate clinical manifestation:
disseminated TB
milliary TB, meningitis TB
tubercle in same size, special
appearance in CXR
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Tuberkulos
is miliaris

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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

LATE COMPLICATIONS
Renal & Skin
Most after 5 years

Most children
become tuberculin
sensitive

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

Uncommon under 5 years of age

25% of cases within 3 months
75% of cases within 6 months

infection

4-8 weeks

3-4 weeks fever of onset

GREATEST RISK OF LOCAL & DISEMINATED LESIONS

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

12 months

Development
Of Complex

Incidence decreases
As age increased

BONE LESION
Most within
3 years

24 months

DIMINISHING RISK
But still possible
90% in first 2 years

Miller FJW. Tuberculosis in children, 1982

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
Collapsed right lower lobe after
Obstruction (Ball-valve)
Complete bronchial obstruction
inflation of Middle & lower lobus
Without consolidation

Erosion into bronchus, inhalarion

And areas of Tub.
Bronchopneumonia

Collapsed after partial

Consolidation segmental
lesion

Pericardial effusion post rupture

of node through percardium

C. Sequelae of bronchial
complication

Stricture of bronchus

Wedge shadow with fibrosis and

bronchiectasis following contracture
of segmental lesion

Cylindrical bronchiectasis in area

Of old collapse

Linear scar of fibrosis following

segmental lesion

Manifestasi klinis
vary, wide spectrum
factors:
TB bacilli: numbers, virulence
host: age, immune state

clinical manifestation
general manifestation
organ specific manifestation
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Manifestasi klinis . . Gejala umum

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

Manifestasi klinis . .. .gejala spesifik

Respiratorik : batuk, sesak, mengi

Nerologik
: kejang, kaku kuduk
Ortopedik
: gibbus, pincang
Kelenjar
: membesar, skrofuloderma
Gastrointestinal
: diare berlanjut
Lain-lain

Manifestasi klinis . . .klasifikasi

Infection:

TST (+), clinical (-), radiographic (-)

Disease:
Pulmonary:

primary pulmonary TB
milliary TB
pleuritis TB
progr primary pulm TB: pneumonia, endobr TB

Extrapulmonary:

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lymph nodes
brain & meninges
bone & joint
gastrointestinal
other organs
50

Manifestasi klinis
......
Infection
klasifikasi
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)
I

Time after
primary
infection

Tuberculin Test Positive

3 12 months

Primary pulmonary TB
TB Meningitis
Miliary TB
TB Pleural effusion

6 24 months

Osteo-articular TB

> 5 years

Phlyctenular conjunctivitis

Fever of Onset

Erythema nodosum

2 3 months

Manifestasi klinis . . . .

Renal TB

Figure 5. The Timetable of

Tuberculosis
Donald PR et.al. In: Madkour MM, ed. Tuberculosis. Berlin; Springer;2003.p.2
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Manifestasi / gambaran klinis

5-10% anak terinfeksi tbc sakit tbc
Gambaran klinis tbc tgt : jumlah basil tbc,
virulensi, umur penderita, imunokompe
tensi, kerentanan pend.saat infeksi
Pd.permulaan tak ada gejala/tanda, kmd
dapat batuk, anoreksi, penurunan BB, panas subfebril. Selanjutnya gejala umum dan
spesifik tgt alat yg terkena (paru, dll.)

Manifestasi klinis ( lanjutan )

Permulaan tbc primer sukar diketahui, sebagian besar gambaran rontgen normal, tak
ada tanda fisik dan laboratorik, hanya tes
tuberculin (+)/Mantoux test.
Panas kadang menyerupai tifus abdominalis, atau malaria
Dapat menunjukkan gjl=bronkopneumoni

Diagnosis (1). . . . . .The main problems

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

Adherence / compliance
Drug discontinuation treatment failure
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Diagnosis (2)
1.
2.
3.
4.
5.
6.
7.
8.
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Anamnesis - Clinical manifestation

Tuberculin skin test
Chest X ray
Microbiologic
Pathology
Hematological
Known infection source
Others : serologic, lung function,
bronchoscopy
56

Anamnesis
Febris lama
Batuk lama
BB

Sumber penularan :

Lesu

Sulit

Aktifitas

Penting :
Untuk dx
Berhasil/tidaknya tx

Phisik Diagnostik
Tbc primer : sering asymptomatik
Gx. Paru/r : ~ INFEKSI LAIN

Cari
Tbc extrathoracal

Scrofuloderma

Cold absces
Tbc tulang/
Sendi

Pembesaran
kelenjar
Men-ser

Conjunctivitis
phlyctenularis

Mantoux Test (1)

Sangat penting untuk diagnostik
Dipakai :
Ot 0,9 mg
Ppd 5 tu
R
Tidak spesifik
Foto bersih : tidak menyangkal ada proses
Dx. TBC TIDAK DAPAT DIBUAT ATAS DASAR r
Persangkaan kuat tbc :
Gbr miliair
Pembesaran kelenjar paratracheal

Mantoux Test (2)

(UJI TUBERKULIN)

Tuberkulin :komponen protein kuman tuberkulosis

yg mempunyai sifat anti- genik yg kuat.
Uji tuberkulin : alat diagnostik TB yg sudah sangat
lama dikenal.
Mempunyai nilai
diagnostik dg sensi-tifitas dan spesifisitas > 90%.
Tuberkulin yg tersedia di Indonesia : PPD RT 23
2TU dan PPD S 5TU.

Mantoux Test (3)

Children for whom immediate Tuberculin Skin

Test (TST) is indicated
1.
2.
3.
4.

Contacts with confirmed or suspected TB

Radiographic/clinical findings suggestive of TB
Children from endemic regions (Asia, Lat. America,
Africa, Middle East)
Children with travel to those regions or contact with
someone from those regions

Mantoux Test (4):

The TST is the only practical tool for TB
diagnosis when asymptomatic
5 tuberculin units of purified protein derivative
(PPD) is the only acceptable method
27 ga. TB syringe
intradermally on the
volar surface

Mantoux Test (5):

TST interpretation
Read induration (not erythema) at 48-72 o
transverse to the long axis of the arm

Ball point pen-method (Sokal) is preferred

Self interpretation is unacceptable
+ tests sometimes persist for several wk

Mantoux Test (6)

Positive PPD defined
(infants, children, adolescents)

Induration 5 mm
Children in close contact with known/suspected
case of TB
Children suspected to have TB
CXR findings
Clinical findings c/w TB

Children receiving immunosuppressive Tx or with

immunosuppressive conditions (e.g. HIV)

Mantoux Test (7)

Positive PPD defined
(infants, children, adolescents)

Induration 10 mm
Children at inc. risk of disseminated Dz
< 4 y/o
Those with Hodgkin's, lymphoma, DM CRF,
malnutrition

Children w/ increased exposure (travel, country of

origin, exposure to high-risk adult)

Mantoux Test (8)

Positive PPD defined
(infants, children, adolescents)

Induration 15 mm
Children > 4 y/o with no risk factor (i.e. all
patients)

INTERPRESTASI
INTERPRESTASI mtx
mtx
0-4 mm
NEGATIF

> 10
mm
POSITIF

5-9 ragu

Klinis :
sedang/pern
ah terinfeksi

Klinis : infeksi

Tidak perlu diulang,

kecuali ada dugaan keras
tbc

Klinis :
-Teknik
salah
-Ada infeksi
-Cross
reaksi
Psot bcg/crp

Aktif,
bila :
< 6 th
Tx
Bcg

Diulang dgn dosis

sama
> 10
mm
Infeksi
Ket : konversi

Teta
p

Tetap tanda-tanda lain

Cross reaksi post bcg

:I. 0 2 mm
II. BERTAMBAH > 10 mm

Konverse
:

Dlm 1 th
Tx
Bcg

MUNGKIN skl TBC

Prinsip dasar Uji Tuberkulin (1)

Infeksi M.tuberculosis sel limfosit T
berproliferasi, tersensitisasi masuk ke aliran
darah, bersirkulasi berbulan-bulan/tahun.
Proses sensitisasi terjadi dlm kel.getah bening
regional (2-12 jam stl. infeksi).
Injeksi tuberkulin pd kulit menstimulasi sel
limfosit aktivasi rentetan kejadian respons
hipersensitivitas tipe lambat (delayed-type
hypersensitivity/DTH )/ memerlukan waktu
berjam-jam.

Prinsip dasar Uji Tuberkulin (2)

Reaktivitas kulit : vasodilatasi,edema,
infiltrasi sel-sel limfosit, basofil,mono-sit
dan netrofil ke lokasi suntikan.
Antigen-spesific limfosit T akan berproliferasi dan melepaskan limfokin, yg
akan mengundang akumulasi sel-sel lain ke
lokasi suntikan terjadi indurasi yg
mencerminkan aktivitas DTH.

Prinsip dasar Uji Tuberkulin (3)

Immune Response to Tuberculin

TB infected :

T lymphocytes proliferate and become

sensitized.
Within weeks these sensitized T cells are
circulating in the blood stream.

Sensitized of lymphocytes

reach a level adequate to produce a

detectable DTH response at 2-10 weeks after
initial infection with M. tuberculosis

This sensitivity may persist for years,

although reactivity may wane
with
CID 1993;17:968-75.

Mantoux
tuberculin
skin test

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Anergi (1)
Uji 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

Anergy (2)
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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Pemeriksaan radiologis (1)

Pemeriksaan rontgen saja tidak dapat
digunakan untuk mendiagnosis tbc.
Gambaran rontgen paru tbc anak ti-dak
khas.
Foto rontgen paru yang normal (tidak
terdeteksi) tidak dapat menyingkirkan
diagnosis TB.

Pemeriksaan radiologis (2)

Secara umum gambaran radiologis yang
sugestif TB adalah sbb.:
*pembesaran
kel.hilus atau paratrakeal
* konsolidasi segmental/lobar
*milier
*kalsifikasi
*atelektasis
*kavitas
* efusi pleura

Pemeriksaan radiologis (2-A)

Should evaluate AP, Lateral views

Nodal component changes
: hilar or mediastinal lymphadenopathy
Lung parenchymal changes
: segmental pneumonia
: segmental hyperinflation
: atelectasis
: effusion, cavitation (rare)

Pemeriksaan radiologis (3)

Jika dijumpai ketidaksesuaian antara
gambaran klinis (ringan) dengan
gambaran radiologis (berat), harus
dicurigai TB.
Pada keadaan foto rontgen paru tidak
jelas, bila perlu dilakukan pencitraan lain
seperti CT-scan toraks.

Gambaran radiologi (1)

Imaging diagnostic

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

Gambaran radiologi ( 2)

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

Gambaran radiologi (3)

Radiographic picture

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primary complex: lymph node enlargement

milliary
atelectasis
cavity
tuberculoma
pneumonia
air trapping - hyperinflation
pleural effusion
honeycombs bronchiectasis
calcification, fibrosis
83

Gambaran radiologi (4)

Radiographic picture
do not always help, particularly in small children
at times can be confusing
some cases: extensive disease from radiography
clinical exam revealed little or nothing
more confusingsuperadded bacterial pneumonia

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Osborne CM et.al. Arch Dis Child 1995;72:369-74

84

Gambaran radiologi (5)

Radiographic picture
No radiographic picture is typical of TB
Many lung diseases have similar radiographic
appearances mimicking PTB
Cannot distinguish active pulmonary TB inactive
PTB previously treated TB
May not detect early stages of TB disease
under-reading
over-reading
intra-individual inconsistency

11/03/15

Vijayan VK. Indian J Clin Biochem 2002;17(2):96-100.

85

Gambaran radiologi (6)

Commonly found: enlargement of hilar/
paratracheal nodes sometimes difficult to
interpret requires thorax CT with contrast
Thorax CT reveals enlargement of lymph
node in 60% children with TB infection and
normal Chest rntgenogram
Delacourt C et.al. Arch Dis Child 1993;69:430-2.

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86

Gambaran CT toraks
NOT ROUTINELY RECOMMENDED
More useful in highly suspected PTB but
normal CXR,
: endobronchial TB
: early cavitation
: bronchiectasis
Very useful in TB meningitis, Tuberculoma,
intrathoracic mass, intraabdominal mass
intraspinal mass

Pleural effusion

Milliary tuberculosis

A 1-year-old with endobronchial TB with

pulmonary consolidation.

3 mo old with TB. Presented as fever. CXRRUL

consolidation. PPD was positive.
Mycobacterium tuberculosis grew from gastric aspirate
culture.

 Primary pulmonary
TB with pleural
effusion (right lung).
The possibility of TB
should routinely be
considered in children
with a pleural effusion

Pemeriksaan mikrobiologis

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

Pemeriksaan mikrobiologis

culture (Lowenstein Jensen)

confirm the diagnosis
negative result do not rule out TB
positive result : 10 - 62 % (old method)
methods:
old method
radiometric (Bactec)
PCR

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96

Pemeriksaan mikrobiologiss
PCR (Polymerase chain reaction )
from gastric aspirate diagnosis of TB in
children
Sensitivity: 44 90%
Specificity: 94 96,8%
Compared to MTB culture
Lodha R et.al. Indian J Pediatr 2004;71:221-7.

PCR technique using primer containing IS6110

better results
Khan EA and Starke JR. Emerg Infect Dis 1995;1:115-23.

May help in early detection of resistant strain of MTB

Lodha R et.al. Indian J Pediatr 2004;71:221-7.

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97

Pemeriksaan serologis
Sensitivity: 19 68%
Specificity: 40 98%

Depends on:
Type of antigen used
Type of infection

Disadvantages
results affected by factors such as
- age
- history of BCG vaccination
- exposure to atypical Mycobacteria
- unable to differentiate between infection and disease
Khan EA and Starke JR. Emerg Infect Dis 1995;1:115-23 .

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98

Pemeriksaan hematologis
Not specific
BSR could elevate
Limphocyte could increase

Pemeriksaan patologis

11/03/15

complicated pathogenesis
varied pathology
clinical manifestation
radiologic appearance
lung represent
tubercle, granuloma, tuberculoma, fibrosis,
fistula, cavity, atelectasis
complication of primary focus: so many
possibilities
100

Pemeriksaan patologis
Lesions of pulmonary tuberculosis
Lymph nodes--hilar, paratracheal, and mediastinal
adenopathy
Parenchyma--primary parenchymal focus, pneumonia,
atelectasis, tuberculoma, cavitary
Airway--air trapping, endobronchial disease,
tracheobronchitis, bronchial stenosis, bronchopleural
fistula, bronchiectasis, bronchoesophageal fistula
Pleura--effusion, bronchoplueral fistula, empyema,
pneumothorax, hemothorax
Blood vessels--miliary, pulmonary hemorrhage
Inselman LS. Tuberculosis in children : An Update. Pediatr Pulmonol 1996; 21:101-20

Pathology jungle
reg lymph node

primary focus

resolution

tubercle formation

caseation

calcification

compresses airway

fibrosis

remote foci

milliary seed

granuloma

tuberculoma
liquefaction

cavity

erodes airway

br pl fistula
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bronchiectasis

2nd lung lesions

rupt to pleura

rupt to airway
102

Pemeriksaan lain-lain

Uji faal paru

Bronkoskopi
Bronkografi
Serologi
MPB64

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 limfogen
4. Per kontinuitatum

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

Pleuritis TB dengan efusi

Pleuritis TB biasanya dengan efusi
Terjadi karena :
Perluasan fokus TB dekat pleura
Penyebaran hematogen

Hipersensitivitas terhadap tuberkulin

pleura
Pungsi pleura
Dapat berupa empyema

efusi

Akibat pembesaran kelenjar

Menekan bronkus :
Atelektasis
Emfisema

Menembus bronkus :
Penyebaran bronkogen
Fistula

TB Tulang dan Sendi

Spondilitis
Koksitis
Gonitis
Daktilitis (Spina ventosa)

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

TB Mata
TB primer konjungtiva
pembesaran
kelenjar preaurikuler
TB koroid funduskopi
Conjunctivitis phluctenularis :
Fenomena hipersensitivitas
Sakit, sangat mengganggu
Rekuren
Terjadi dalam 5-15 tahun

Masalah dalam diagnosis TB anak

If you find the diagnosis of TB in children easy, you
probably overdiagnosing TB
If you find the diagnosis of TB in children difficult,
you are not alone
It is easy to over-diagnose TB in children
It is also easy to miss TB in children
Carefully assess all the evidence, before making the
diagnosis

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Anthony Harries & Dermot Maher, 1997

120

Pengobatan
Objectives of treatment
Rapid reduction of the number
of bacilli
Preventing acquired drug
resistance
Sterilization to prevent relapses

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122

Pengobatan
Treatment principles
Drug combination, not single drug
risk of fall and rise phenomenon
each TB drug has special action to certain
TB bacilli population

Two phases :
Initial phase (2 months) intensive,
bactericidal effect
Maintenance phase (4 months / more)
sterilizing effect, prevent relaps
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123

Pengobatan
Treatment principles

Long duration problem of

adherence (compliance)
Other aspects :
Nutrition improvement
prevent / search & treat other
disease
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124

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)

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

Dosage of antituberculosis drug

Drugs

Daily dose
(mg/Kg/day)

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

Adverse reactions

Isoniazid
(INH)

5-15
(300 mg))

15-40
(900 mg))

Hepatitis, peripheral neuritis,

hypersensitivity

Rifampicin
(RIF)

10-15
(600 mg))

10-20
(600 mg)

Gastrointestinal upset,skin reaction,

hepatitis, thrombocytopenia,
hepatic enzymes, including orange
discolouraution of secretions

Pyrazinamide
(PZA)

15 - 40
(2 g)

50-70
(4 g)

Hepatotoxicity, hyperuricamia,
arthralgia, gastrointestinal upset

Ethambutol
(EMB)

15-25
(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)

Ototoxicity nephrotoxicity

When INH and RIF are used concurrently, the daily doses of the drugs are reduced
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127

National consensus of tuberculosis in children, 2001

Daftar obat dan dosisnya

Nama Obat

BB < 10 Kg

BB 10-20 Kg BB 20-33 Kg

INH (H)

50 mg

100 mg

200 mg

Rifampisin (R)

75 mg

150 mg

300 mg

150 mg

300 mg

600 mg

PZA (Z)

Bila BB > 33 kg dimasukkan golongan dewasa

Bila BB < 5 kg sebaiknya dirujuk ke Rumah sakit
Bila dikombinasikan H dan R, H tidak boleh lebih dari 10
mg/Kg BB/hari, R tidak boleh lebih dari 15 mg/Kg
INH dan rifampisin tidak boleh diracik dalam satu puyer,
tetapi boleh dicampur saat meminumnya

Fixed Dose Combination

Regimen of Antituberculosis drugs

2 mo

6 mo

9 mo

12 mo

INH
RIF
PZA
EMB
STREP
PRED

Directly Observed Treatment Short course (DOTS)

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

Evaluasi pengobatan
Clear improvement in clinical
and supporting examination,
especially in the first 2 month
Main : clinical
supporting exam as adjuvant
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132

Evaluasi pengobatan
Clinical improvement :
Increased body weight
Increased appetite
Diminished / reduced symptoms (fever, cough,
etc)

Supporting examination :
Chest X rays : 2 / 6 month (on indication)
Blood : BSR
Tuberculin test : once positive, do not needed to
repeat !
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133

Kegagalan pengobatan
Inadequate response, despite adequate
therapy :
Review the diagnosis, not a TB case ?
Review other aspects : nutrition, other
disease
MDR rarely in children

Treatment discontinuation
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134

Permasalahan dlm pengobatan

The main : compliance / adherence (kebutuhan /
dosis /ketaatan)
The factors :
Long duration
Drug side effect
Initial improvement misinterpreted by patients /
parents
Inconvenient health service
Socio-economic-cultural factors

The following : drug resistance

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135

Penanganan masalah kegagalan pengobatan

DOTS : Directly Observe Treatment
Shortcourse
FDC : Fixed dose combination i.e. >2
drugs in one tablet in a fixed dose
formulation

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136

DOTS with a SMILE

S
M
I
L
E

: Supervised
: Medication
: In
: a Loving
: Environment

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

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137

Fixed Dose Combination

FDC: >2 drugs in one tablet in a fixed
dose formulation
simple dosing
patient friendly, doctor friendly
increase adherence
reduce MDR
easier drug supplying
easier drug monitoring
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138

FDC tablet formulation

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

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

139

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
11/03/15

Intensive, 2 mo Continuation, 4 mo
(tablet)
(tablet)
1
1
1,5
1,5
2
2
3
3
4
4
5
5
140

IDAI FDC (H/R/Z:50/75/150

&

H/R:50/75)

BW
(kg)

Intensive, 2
mo
(tablet)

Continuation, 4 mo
(tablet)

5-9
10-19
20-33

1
2
4

1
2
4

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

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141

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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142

Pencegahan
Perbaikan sosio ekonomi
Kemoprofilaksis
Imunisasi BCG

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

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

Imunisasi BCG

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

Selamat
belajar