Tuberkulosis Anak

Dr. Dewi Angreany M.Ked(Ped), Sp.A

 Definition
Tuberculosis is a disease due to
Mycobacterium tuberculosis infection with
systemic spread thus can affect almost all
organs, and the most frequent site is in the
lung, which usually as the site of primary
infection

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 Magnitude of problem
O TB one of the oldest diseases of human
O remains one of the deadliest diseases in the
world
O 8 million of new cases yearly
O 3 million death yearly
O 20-40% population is infected
O reemergence, global emergency

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 The main problems
O Diagnosis
O Clinical manifestations : not specific  both
over/under diagnosis & over/under treatment
O diagnostic specimen : difficult to obtain
O TB infection or TB disease ?  no diagnostic tool
to distinguish
O Adherence / compliance
O Drug discontinuation  treatment failure

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 Etiology
O Mycobacterium tuberculosis
O 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) 2/14/2019 5
 M tuberculosis
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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 Transmission
O airborne human to human transmission by
droplet nuclei
O adult pulmonary TB: cough, sneeze, speak, or
sing
O droplet nuclei : contain 2-3 bacilli, small size (1-
5) keep in the air for long period
O inhalation, reach alveoli
O middle and lower lobes
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TB droplet nuclei

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 Transmission factors:
O doses / numbers
O concentration in the air
O virulence
O exposure duration
O host immune state
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Transmission rate (Shaw ’54)

adult
TB patient

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

65% 26% 17%

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 droplet nuclei alveoli ingestion by PAM’S
inhalation

intracellular replication
of bacilli
destruction
destruction of PAM’S 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 2/14/2019

CMI
11
disseminated primary TB remote foci

Figure. Pathogenesis of primary tuberculosis

 Incubation period
O first implantation  primary complex
O 4-6 weeks (2-12 weeks)  incubation period
O end of incubation period:
O primary complex formation
O cell mediated immunity
O tuberculin sensitivity
 PrimaryTB infection has established

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Pathogenesis ...
lymphadenitis

lymphangitis

primary focus

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 Primary complex
O end of incubation period
O TB infection establishment
O tuberculin sensitivity (DTH)
O cell mediated immunity
O end of hematogenic spread
O end of TB bacilli proliferation
O small amount, live dormant in granuloma
O new exogenous TB bacilli: destroyed / localized
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TB Natural history overview
primary TB infection

primary TB disease latent infection

post primary TB no disease

non respir TB respiratory TB

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new infection
 Pathology
O complicated pathogenesis
varied pathology
clinical manifestation
radiologic appearance
O lung represent
O tubercle, granuloma, tuberculoma, fibrosis,
fistula, cavity, atelectasis
O complication of primary focus: so many
possibilities
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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 to17airway

rupt to pleura2/14/2019
br pl fistula
 Clinical types of pediatric TB
O Infection: TST (+), clinical (-), radiographic (-)
O Disease:
O Pulmonary:
O primary pulmonary TB
O milliary TB
O pleuritis TB
O progr primary pulm TB: pneumonia, endobr TB
O Extrapulmonary:
O lymph nodes
O brain & meninges
O bone & joint
O gastrointestinal
O other organs
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 General manifestation
O chronic fever, subfebrile
O anorexia
O weight loss
O malnutrition
O malaise
O chronic recurrent cough, think asthma!
O chronic recurrent diarrhea
O others 2/14/2019 19
 Organ specific
O Respiratory : cough, wheezing, dyspnea
O Neurology : convulsion, neck stiffness,
SOL manifestation
O Orthopedic : gibbus, crippled
O Lymph node : enlarge, scrofuloderma
O GIT : chronic diarrhea
O Others

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

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

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 Radiographic picture
O primary complex: lymph node enlargement
O milliary
O atelectasis
O cavity
O tuberculoma
O pneumonia
O air trapping - hyperinflation
O pleural effusion
O honeycombs – bronchiectasis
O calcification, fibrosis
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 Serology
Depends on:
Sensitivity: 19 – 68% Type of antigen used
Type of infection
Specificity: 40 – 98%

Disadvantages
results affected by factors such as
- age
- history of BCG vaccination
- exposure to atypical Mycobacteria
- unable to differentiate between infection and disease
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Khan EA and Starke JR. Emerg Infect Dis 1995;1:115-23.
 Polymerase chain reaction
O PCR
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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 Diagnosis
1. Tuberculin skin test
2. Chest X ray
3. Clinical manifestation
4. Microbiologic
5. Pathology
6. Hematological
7. Known infection source
8. Others : serologic, lung function,
bronchoscopy
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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
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etiologies
 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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Algorithm for Early Detection and Referral for Childhood
Tuberculosis in Indonesia
Suspected TB:
O Close contact with adult with AFB sputum (+)
O Early reaction of BCG (in 3-7 days)
O Weight loss with no apparent cause, or underweight with no
improvement in 1 month with adequate nutritional support (failure to
thrive)
O Prolonged/recurrent fever with no apparent cause
O Cough more than 3 weeks
O Specific enlargement of superficial lymph node
O Scrofuloderma
O Flychten conjunctivitis
O Tuberculin test positive (> 10 mm)
O Radiological findings suggestive TB

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If > 3 positive Next page
 Considered TB

Give anti-TB therapy

Observation in 2 months

Clinical response (+) No clinical response/worsening

TB Not TB MDR TB

Continue anti-TB therapy Refer to hospital

ATTENTION
Presence of any dangerous signs: Reevaluation in Referral Hospital:
• Seizure Clinical signs
• Decreased level of consciousness Tuberculin test
• Neck stiffness Radiological findings
Or signs such as: Microbiology and serology examination
• Spinal tumor/lump Histopatology examination
• Limping Diagnostic procedure and therapy
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• Dam board phenomenon to each hospital’s protocol
 Send to hospital
UKK Pulmonologi –IDAI. Jakarta;2002.
Notes for IDAI scoring system
O Diagnosis by doctor
O BW assessement at present
O Fever & cough no respons to standard tx
O CXR is NOT a main diagnostic tool in children
O All accelerated BCG reaction should be evaluated with
scoring system
O TB diagnosis total score >5
O Score 4 in under5 child or strong suspicion, refer to
hospital
O INH prophylaxis for AFB(+) contact with score <5

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 Objectives of treatment
O Rapid reduction of the number of
bacilli
O Preventing acquired drug
resistance
O 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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 Treatment principles
 Long duration  problem of
adherence (compliance)
 Other aspects :
 Nutrition improvement
 prevent / search & treat other
disease
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 Dosage of antituberculosis drug
2 Time/week
Daily dose
Drugs (mg/Kg/day)
dose Adverse reactions
(mg/Kg/dose))
Isoniazid 5-15 15-40 Hepatitis, peripheral neuritis,
(INH) (300 mg)) (900 mg)) hypersensitivity
Gastrointestinal upset,skin reaction,
Rifampicin 10-15 10-20 hepatitis, thrombocytopenia,
(RIF) (600 mg)) (600 mg) hepatic enzymes, including orange
discolouraution of secretions

Pyrazinamide 15 - 40 50-70 Hepatotoxicity, hyperuricamia,

(PZA) (2 g) (4 g) arthralgia, gastrointestinal upset

Optic neuritis, decreased visual

Ethambutol 15-25 50 acuity, decreased red-green colour
(EMB) (2,5 g) (2,5 g) discrimination, hypersensitivity,
gastrointestinal upset

Streptomycin 15 - 40 25-40
Ototoxicity nephrotoxicity
(SM) (1 g) (1,5 g)
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When INH and RIF are used concurrently, the daily doses of the drugs are reduced

National consensus of tuberculosis in children, 2001

 TB therapy regimen
2 mo 6 mo 9 mo 12mo

INH
RIF
PZA

EMB
SM

PRED
DOT.S !

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 Corticosteroid
O Anti inflammation
O prednison : 1 - 3 mg/kg BB/hari, 3x/hari
oral 2 - 4 minggu, tapering off
O Indications :
O TB milier
O Meningitis TB
O Pleuritis TB with effusion

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 Treatment evaluation
O Clinical improvement :
O Increased body weight
O Increased appetite
O Diminished / reduced symptoms (fever, cough, etc)
O Supporting examination :
O Chest X rays : 2 / 6 month (on indication)
O Blood : BSR
O Tuberculin test : once positive, do not needed to repeat !

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 Treatment failure
O Inadequate response, despite adequate therapy
:
O Review the diagnosis, not a TB case ?
O Review other aspects : nutrition, other disease
O MDR – rarely in children
O Treatment discontinuation

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 Treatment problems
O The main : compliance / adherence
O The factors :
O Long duration
O Drug side effect
O Initial improvement – misinterpreted by patients /
parents
O Inconvenient health service
O Socio-economic-cultural factors
O The following : drug resistance
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 Pencegahan
O Perbaikan sosio ekonomi
O Kemoprofilaksis
O Imunisasi BCG

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

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 Kemoprofilaksis sekunder
Mencegah penyakit TB pada anak yang
terinfeksi :
1. Mantoux (+), Rö (-), klinis (-) :
O Umur < 5 th
O Kortikosteroid lama
O Limfoma, Hodgkin, lekemi
O Morbili, pertusis
O Akil baliq
2. Konversi Mt (-) menjadi (+) dalam 12 bl, Rö
(-), klinis (-)
Obat INH 5 - 10 mg/kg BB/hari
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 Imunisasi BCG
O Imunitas spesifik
O Uji tuberkulin menjadi (+)
O Mt (-) baru BCG
O Masal : langsung BCG tanpa Mt
O Reaksi lokal : membantu screening

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 Thank you

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