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04/21/23 1
CHILDHOOD TB
04/21/23 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
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
04/21/23 7
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
04/21/23 10
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
04/21/23 11
Tuberculin testTB infection
cellular immunity
delayed type hypersensitivity
tuberculin reaction
04/21/23 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
04/21/23 13
Mantoux tuberculin skin test
04/21/23 14
TB classification (ATS/CDC modified)
Class Contact Infection Disease Manage
ment
0 - - - -
1 + - - proph I
2 + + - proph II?
3 + + + therapy
04/21/23 15
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
04/21/23 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
04/21/23 17
Clinical manifestation
• vary, wide spectrum
• factors: – TB bacilli: numbers, virulence– host: age, immune state
• clinical manifestation– general manifestation– organ specific manifestation
04/21/23 18
General manifestation
• chronic fever, subfebrile• anorexia• weight loss• malnutrition• malaise• chronic recurrent cough, think asthma!• chronic recurrent diarrhea• others
04/21/23 19
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
04/21/23 20
Organ specific • Respiratory: cough, wheezing, dyspnea• Neurology : convulsion, neck stiffness,
SOL manifestation • Orthopedic : gibbus, crippled• Lymph node : enlarge, scrofuloderma• Gastrointestinal: chronic diarrhea• Others
04/21/23 21
Imaging diagnostic
• routine : chest X ray
• on indication : bone, joint, abdomen
• majority of CXR non suggestive TB
• pitfall in TB diagnostic
04/21/23 22
Radiographic picture
• primary complex: lymph node enlargement• milliary• atelectasis• cavity• tuberculoma• pneumonia• air trapping - hyperinflation• pleural effusion• honeycombs – bronchiectasis• calcification, fibrosis
04/21/23 23
100
32
0
20
40
60
80
100
Diagnosed by X-ray alone
Actual cases
Over diagnosis TB by CXR
Over-diagnosis
04/21/23 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
04/21/23 25
Clinical setting management Suspect
TBproveTB infection
Mantoux test
positive negative
not TB
Seek other etiologies
completed: Ro, labDiagnosis
TBtreatment
04/21/23 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
04/21/23 27
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 - -
04/21/23 28
Objectives of treatment
• Rapid reduction of the number of bacilli
• Preventing acquired drug resistance
• Sterilization to prevent relapses
04/21/23 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
04/21/23 30
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
04/21/23 31
Treatment principles
Long duration problem of adherence (compliance)
Other aspects :Nutrition improvementprevent / search & treat other disease
04/21/23 32
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
04/21/23 33
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
04/21/23 34
TB therapy regimen 2 mo 6 mo 9 mo 12mo
INHRIFPZA
EMBSM
PREDDOT.S !
04/21/23 35
Treatment evaluation
•Clear improvement in clinical and supporting examination, especially in the first 2 month
•Main : clinical•supporting exam as
adjuvant
04/21/23 36
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)
04/21/23 37
Trace
Child TBpatient
Adult TB patient
centri-petal
centri-fugal
04/21/23 38
case findingcentripetal
• trace the source
• adult people• close contact• by chest X ray
centrifugal• trace other
‘victims’• children• close contact• by tuberculin
04/21/23 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
04/21/23 40
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
04/21/23 41
Question pls?