3/14/2013 1

CHILDHOOD TB

3/14/2013 2

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

ARI

AID

S

Dia

rrhe

aTB

Malar

ia

Mea

sles

De

ath

in

millio

ns

Under age 5

Over age 5

3.5

2.3 2.2 1.5

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 50-54

Age (years)

Per

100,0

00 p

op

ula

tio

n

Male

Female

3/14/2013 7

Transmission rate (Shaw ’54)

adult TB 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 HIV

Miller, 1963

3/14/2013 9 Figure. Pathogenesis of primary tuberculosis

droplet nuclei inhalation

alveoli ingestion by PAM’S

intracellular replication of bacilli

destruction of bacilli destruction 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

3/14/2013 10

Incubation period

• first implantation primary complex

• 4-6 weeks (2-12 weeks) incubation period

• first weeks: logaritmic growth, : 103-10

4

elicit cellular response

• end of incubation period:

– primary complex formation

– cell mediated immunity

– tuberculin sensitivity

PrimaryTB infection has established

3/14/2013 11

Tuberculin test

TB infection

cellular immunity

delayed type hypersensitivity

tuberculin reaction

3/14/2013 12

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

3/14/2013 13

Mantoux

tuberculin

skin test

3/14/2013 14

TB classification (ATS/CDC modified)

Class Contact Infection Disease Manage

ment

0 - - - -

1 + - - proph I

2 + + - proph II?

3 + + + therapy

3/14/2013 15

tubercle formation resolution

primary focus

calcification

2nd lung lesions

caseation

liquefaction

granuloma

Pathology

remote foci reg lymph node

tuberculoma

cavity

milliary seed

erodes airway

compresses airway

rupt to pleura rupt to airway bronchiectasis

fibrosis

br pl fistula

3/14/2013 16

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

3/14/2013 17

Clinical manifestation

• vary, wide spectrum

• factors:

– TB bacilli: numbers, virulence

– host: age, immune state

• clinical manifestation

– general manifestation

– organ specific manifestation

3/14/2013 18

General manifestation

• chronic fever, subfebrile

• anorexia

• weight loss

• malnutrition

• malaise

• chronic recurrent cough, think asthma!

• chronic recurrent diarrhea

• others

3/14/2013 19

Fever of Onset

Tuberculin Test Positive

Primary pulmonary TB

TB Meningitis

Miliary TB

TB Pleural effusion

Osteo-articular TB

Renal TB

Ph

lycte

nu

lar c

on

jun

ctiv

itis

Ery

the

ma

no

do

su

m

2 – 3 months

3 – 12 months

6 – 24 months

> 5 years

Time after

primary infection Clinical Manifestation

Figure 5. The Timetable of Tuberculosis

Donald PR et.al. In: Madkour MM, ed. Tuberculosis. Berlin; Springer;2003.p.243-64

3/14/2013 20

Organ specific

• Respiratory : cough, wheezing, dyspnea

• Neurology : convulsion, neck stiffness,

SOL manifestation

• Orthopedic : gibbus, crippled

• Lymph node : enlarge, scrofuloderma

• Gastrointestinal: chronic diarrhea

• Others

3/14/2013 21

Imaging diagnostic

• routine : chest X ray

• on indication : bone, joint, abdomen

• majority of CXR non suggestive TB

• pitfall in TB diagnostic

3/14/2013 22

Radiographic picture

• primary complex: lymph node enlargement

• milliary

• atelectasis

• cavity

• tuberculoma

• pneumonia

• air trapping - hyperinflation

• pleural effusion

• honeycombs – bronchiectasis

• calcification, fibrosis

3/14/2013 23

100

32

0

20

40

60

80

100

Diagnosed by X-

ray alone

Actual cases

Over diagnosis TB by CXR

Over- diagnosis

3/14/2013 24

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

3/14/2013 25

Clinical setting management

Suspect TB

proveTB infection

Mantoux test

positive negative

not TB

Seek other etiologies

completed: Ro, lab Diagnosis TB

treatment

3/14/2013 26

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

3/14/2013 27

Proposed IDAI scoring system

Feature 0 1 2 3 Score

Contact not clear reported, AFB(-)

- AFB(+)

TST - - - positive

BW (KMS) - <red line, BW

severe malnutrition

-

Fever - unexplained - -

Cough <3weeks >3weeks - -

Node enlargemnt

- >1 node, >1cm,painless

- -

Bone,joint - swelling - -

CXR normal sugestive - -

3/14/2013 28

Objectives of treatment

• Rapid reduction of the number

of bacilli

• Preventing acquired drug

resistance

• Sterilization to prevent relapses

3/14/2013 29

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

3/14/2013 30

Smear +

Culture +

Smear -

Culture +

Smear -

Culture -

108

107

106

105

104

103

102

101

100

Start of treatment

(isoniazid alone) Weeks of treatment

0 3 6 9 12 15 18 WHO 78351

Sensitive organisms Resistant organisms

Nu

mb

er

of

bacil

li p

er

ml o

f sp

utu

m

Toman K, Tuberculosis, WHO, 1979

The ‘fall and rise’ phenomenon

3/14/2013 31

Treatment principles

Long duration problem of

adherence (compliance)

Other aspects :

Nutrition improvement

prevent / search & treat other disease

3/14/2013 32

Hypothetical model of TB therapy

A

B

C

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

3/14/2013 33

Drug activities upon TB pop

TB Population

Multiplying rate

Drug

activities

A rapidly INH>>SM>

RIF>EMB

B slowly PZA>>RIF>>

INH

C sporadically RIF>>INH

3/14/2013 34

TB therapy regimen

2 mo 6 mo 9 mo 12mo

INH

RIF

PZA

EMB

SM

PRED

DOT.S !

3/14/2013 35

Treatment evaluation

• Clear improvement in clinical and supporting examination, especially in the first 2 month

• Main : clinical

• supporting exam as adjuvant

3/14/2013 36

DOTS with a SMILE

S : Supervised

M : Medication

I : In

L : a Loving

E : Environment (Grange JM, Int J Tuberc Lung Dis 1999; 3:360-

362)

3/14/2013 37

Trace

Child TB patient

Adult TB patient

centri- petal

centri- fugal

3/14/2013 38

case finding

centripetal

• trace the source

• adult people

• close contact

• by chest X ray

centrifugal

• trace other ‘victims’

• children

• close contact

• by tuberculin

3/14/2013 39

Kemoprofilaksis primer

• Mencegah infeksi

• Anak kontak dengan pasien TB aktif, tetapi

belum terinfeksi (uji tuberkulin negatif)

• Obat : INH 5 - 10 mg/kg BB/hari

3/14/2013 40

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

3/14/2013 41

Question

pls?