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CHILDHOOD TB

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Childhood TB
Why neglected?
Not considered important in global program or
contributing to immediate transmission
Not regarded as public health risk
Difficult to diagnose
Why is it important?
Health problem in children
May later contribute to epidemic
Childhood TB as Sentinel Event
Indicates recent transmission in a
community
Rapid progression from infection to disease
A deterioration in the control of TB thus
immediately hurts the youngest generation
(Rieder, 1997)
Children are future reservoir of disease

Rieder H. Anales Nestle, 1997


Leading Infectious Disease
Causes of Death, 1998
Death in millions

4 3.5
Under age 5
3 2.3 2.2 Over age 5
2 1.5
1.1 0.9
1
0
S
I

TB

s
a

ria
AR

le
he
AI

s
rr

al

ea
a

M
Di

WHO Report 2000


700
Male
600 Female
Per 100,000 population

500

400

300

200

100

0
<1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 35-39 40-44 45-49 50-54
Age (years)
Transmission rate (Shaw 54)
adult
TB patient

AFB(-) culture(-)
AFB(+) culture(+) CXR (+)

65% 26% 17%

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Risk of Progression to Disease
Age
43% in infants (children < 1year)
25% in children aged one to five years
15% in adolescents
10% in adults
Recent Infection
Malnutrition
Immunosuppression, particularly HIV
Miller, 1963
droplet nuclei
alveoli ingestion by PAMS
inhalation

intracellular replication
of bacilli
destruction
destruction of PAMS of bacilli

Tubercle formation Lymphogenic spread Hilar lymph nodes


primary focus lymphangitis lymphadenitis

hematogenic spread
primary
acute hematogenic occult hematogenic
complex
spread spread

multiple organs
CMI
disseminated primary TB remote foci
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Figure. Pathogenesis of primary tuberculosis
Incubation period
first implantation primary complex
4-6 weeks (2-12 weeks) incubation period
3 4
first weeks: logaritmic growth, : 10 -10
elicit cellular response
end of incubation period:
primary complex formation
cell mediated immunity
tuberculin sensitivity
PrimaryTB infection has established

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Tuberculin test
TB infection

cellular immunity

delayed type hypersensitivity

tuberculin reaction

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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

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Mantoux
tuberculin
skin test

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

0 - - - -
1 + - - proph I

2 + + - proph II?

3 + + + therapy

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Pathology
reg lymph node primary focus remote foci

resolution milliary seed


tubercle formation

calcification caseation granuloma

compresses airway fibrosis tuberculoma

liquefaction
cavity
erodes airway

bronchiectasis 2nd lung lesions rupt to pleura rupt to airway


br pl fistula
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Clinical types of pediatric TB
Infection: TST (+), clinical (-), radiographic (-)
Disease:
Pulmonary:
primary pulmonary TB
milliary TB
pleuritis TB
progr primary pulm TB: pneumonia, endobr TB
Extrapulmonary:
lymph nodes
brain & meninges
bone & joint
gastrointestinal
other organs

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Clinical manifestation
vary, wide spectrum
factors:
TB bacilli: numbers, virulence
host: age, immune state
clinical manifestation
general manifestation
organ specific manifestation

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General manifestation
chronic fever, subfebrile
anorexia
weight loss
malnutrition
malaise
chronic recurrent cough, think asthma!
chronic recurrent diarrhea
others
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Time after
primary infection Clinical Manifestation
2 3 months Fever of Onset

Erythema nodosum

Phlyctenular conjunctivitis
Tuberculin Test Positive

Primary pulmonary TB
TB Meningitis
3 12 months
Miliary TB
TB Pleural effusion

6 24 months Osteo-articular TB

> 5 years Renal TB

Figure 5. The Timetable of Tuberculosis


Donald PR et.al. In: Madkour MM, ed. Tuberculosis. Berlin; Springer;2003.p.243-64
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Organ specific
Respiratory : cough, wheezing, dyspnea
Neurology : convulsion, neck stiffness,
SOL manifestation
Orthopedic : gibbus, crippled
Lymph node : enlarge, scrofuloderma
Gastrointestinal: chronic diarrhea
Others

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

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Radiographic picture
primary complex: lymph node enlargement
milliary
atelectasis
cavity
tuberculoma
pneumonia
air trapping - hyperinflation
pleural effusion
honeycombs bronchiectasis
calcification, fibrosis
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Over diagnosis TB by CXR
100
100
80 Over-
diagnosis
60
40 32

20
0
Diagnosed by X- Actual cases
ray alone
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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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Clinical setting management
Mantoux
Suspect TB test
proveTB
infection positive negative

completed: not TB
Diagnosis TB Ro, lab
Seek other
treatment etiologies
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Diagnosis of TB in children
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

Anthony Harries & Dermot Maher, 1997


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Proposed IDAI scoring system
Feature 0 1 2 3 Score
Contact not clear reported, - AFB(+)
AFB(-)
TST - - - positive
BW (KMS) - <red line, severe -
BW malnutrition
Fever - unexplained - -
Cough <3weeks >3weeks - -
Node - >1 node, - -
enlargemnt >1cm,painless
Bone,joint - swelling - -
CXR normal sugestive - -

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Objectives of treatment

Rapid reduction of the number


of bacilli
Preventing acquired drug
resistance
Sterilization to prevent relapses

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Treatment principles
Drug combination, not single drug
Two phases :
Initial phase (2 months) intensive,
bactericidal effect
Maintenance phase (4 months / more)
sterilizing effect, prevent relaps

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The fall and rise phenomenon
108
Number of bacilli per ml of sputum

107 Sensitive organisms Resistant organisms

106
Smear +
Culture +
105

104
Smear -
Culture +
103

102

101 Smear -
Culture -

100
0 3 6 9 12 15 18 WHO 78351
Start of treatment
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Weeks of treatment 30
(isoniazid alone) Toman K, Tuberculosis, WHO, 1979
Treatment principles
Long duration problem of
adherence (compliance)
Other aspects :
Nutrition improvement
prevent / search & treat other
disease
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Hypothetical model of TB therapy

Pop A = rapidly multiplying (caseum)


A Pop B = slowly multiplying (acidic)
Pop C = sporadically multiplying
B
C

0 1 2 3 4 5 6
Months of therapy

Bacteridal activity & sterilizing effect


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Drug activities upon TB pop
TB Multiplying Drug
Population rate activities

A rapidly INH>>SM>
RIF>EMB

B slowly PZA>>RIF>>
INH

C sporadically RIF>>INH

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TB therapy regimen
2 mo 6 mo 9 mo 12mo

INH
RIF
PZA

EMB
SM

PRED
DOT.S !

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Treatment evaluation

Clear improvement in clinical


and supporting examination,
especially in the first 2 month
Main : clinical
supporting exam as adjuvant

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DOTS with a SMILE
S : Supervised
M : Medication
I : In
L : a Loving
E : Environment
(Grange
11/27/2012 JM, Int J Tuberc Lung Dis 1999; 3:360-36
Trace
Adult TB
patient centri-
fugal

centri-
petal

Child TB
patient

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case finding
centripetal centrifugal
trace the source trace other
adult people victims
close contact children
by chest X ray close contact
by tuberculin

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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 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
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Question
pls?

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