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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

0

1

2

3

4

Dea

th in

mill

ion

s

Under age 5Over age 5

3.5

2.3 2.21.5

1.1 0.9

WHO Report 2000

700

600

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 50-54Age (years)

Per

100

,000

po

pu

lati

on

MaleFemale

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Transmission rate (Shaw ’54)

adultTB patient

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

culture(-)CXR (+)

65% 26% 17%

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

HIVMiller, 1963

04/21/23 9Figure. Pathogenesis of primary tuberculosis

droplet nuclei inhalation alveoli ingestion by PAM’S

intracellular replicationof bacilli

destruction of bacillidestruction of PAM’S

Tubercle formation Hilar lymph nodes

hematogenic spread

multiple organs remote foci

Lymphogenic spread

disseminated primary TB

acute hematogenic spread

occult hematogenic spread

primary focus lymphangitis lymphadenitis

primary complex

CMI

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Incubation period

• 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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Tuberculin testTB 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)

Class Contact Infection Disease Manage

ment

0 - - - -

1 + - - proph I

2 + + - proph II?

3 + + + therapy

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tubercle formationresolution

primary focus

calcification

2nd lung lesions

caseation

liquefaction

granuloma

PathologyPathology

remote focireg lymph node

tuberculoma

cavity

milliary seed

erodes airway

compresses airway

rupt to pleura rupt to airway bronchiectasis

fibrosis

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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Fever of Onset

Tuberculin Test Positive

Primary pulmonary TBTB Meningitis

Miliary TBTB Pleural effusion

Osteo-articular TB

Renal TB

Ph

lycte

nu

lar co

nju

nctiv

itis

Ery

them

a n

od

osu

m2 – 3 months

3 – 12 months

6 – 24 months

> 5 years

Time after primary infection

Clinical Manifestation

Figure 5. The Timetable of TuberculosisDonald 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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100

32

0

20

40

60

80

100

Diagnosed by X-ray alone

Actual cases

Over diagnosis TB by CXR

Over-diagnosis

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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 Suspect

TBproveTB infection

Mantoux test

positive negative

not TB

Seek other etiologies

completed: Ro, labDiagnosis

TBtreatment

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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

clearreported,

AFB(-)- AFB(+

)

TST - - - positive

BW (KMS) - <red line, BW

severe malnutritio

n

-

Fever - unexplained - -

Cough <3weeks

>3weeks - -

Node enlargemn

t

- >1 node, >1cm,painle

ss

- -

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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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

The ‘fall and rise’ phenomenon

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Treatment principles

Long duration problem of adherence (compliance)

Other aspects :Nutrition improvementprevent / search & treat other disease

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Hypothetical model of TB therapy

A

BC

Bacteridal activity & ‘sterilizing’ effect

0 1 2 3 4 5 6

Pop A = rapidly multiplying (caseum)

Pop B = slowly multiplying (acidic)

Pop C = sporadically multiplying

Months of therapy

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Drug activities upon TB pop

TB Populatio

n

Multiplying rate

Drug 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

INHRIFPZA

EMBSM

PREDDOT.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 SMILES : 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)

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Trace

Child TBpatient

Adult TB patient

centri-petal

centri-fugal

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case findingcentripetal

• trace the source

• adult people• close contact• by chest X ray

centrifugal• trace other

‘victims’• children• 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 sekunderMencegah 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

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Question pls?