1

Tuberculosis in childrendr. Ery Olivianto, SpA

Dr. dr. Wisnu Barlianto, SpA(K)Prof. Dr. dr. HMS. Chandra Kusuma, SpA(K)

Child Health Department Faculty of Medicine Brawijaya UniversitySaiful Anwar General Hospital

2

Back Ground

WHO : 1990 – 1999 30 millions died1/3 world population infectedPer year 8 milions new cases

3 milions die5 – 10% infected active TB Eradication is difficult : MDR HIV Pandemi BCG : various protection rate

3

Mycobacterium tuberculosis colony

4

M.Tb cell wall stucture

5

Pathogenesis of TB

6

Mechanism of T cell activation Killing of M.Tb bacteria

7

Granuloma formation

8

Granuloma (Tubercle)

replication of bacteriaThe process is confined

Characteristic feature of TB :Caseating centreExtracellular bacteriaCells :

macrophageEpiteloid cellsT cellsGiant cells of Langhans

Central for protection

9

Pathogenesis of TB infection

10

Primary focus:Structural and cellular changes due to response to multiplication of M.Tb in tissues first to be implanted usually lungs

Primary adenitis = regional lymphadenitisChanges in lymphnode secondary to drainage from primary focus

Primary nodes :Anatomic reflection of primary focus

Primary complex :Primary focus + regional lymphadenitis

11

12

infection

primary complex

pleural effusion

bronchial erosion

Milliary TBMeningitis Skeletal TB Renal TB

2-12 wks(6-8 wks)

3-24 mos 3-6 mos 3-9 mos within 12 mos within 3 ys within 5 ys

Hypersensitivity Acquired immunity

Positive TST

1 year

greatest risk of locals and disseminated lesion

diminishing risk

2 year

13

Primary focus undergo caseation

Focus enlarged disrupted to bronchus cavity

Caseation depends on:

Host immunity

Nutrition

Amount of bacteria and its virulence

Round/coin lesions (>>)

persisted

calsification 1 years

14

AGE-SPECIFIC RISK TO PROGRESS TO DISEASE AFTER PRIMARY INFECTION WITH Mycobacterium tuberculosisIN IMMUNOCOMPETENT CHILDREN

15

primary focus

regional lymphadenitis

hematogenic spread

Time table

16

Primary focus : Usually single

One /both lung(s)

near pleura Sensitization :

4 – 8 wks after infectiondepends on :

age nutrition

Phenomena of sensitization :

1. Febrile illness lasting 2-3 wks

2. Phlyctenularis conjuctivitis

3. Erythema nodosum

17

Essential sensitivity reaction

Massive effusion is rare for < 5 years

75% 6 months after infection

25% 3 months after infection

Usually serous (empyema )

Pleural Effusion

18

1. Miliary dan meningitis TB

Within 1st year after infection

More common in younger age

Decreased immunity :MalnutritionHIV infection MeaslesPertussisStreptococcus infection

Hematogenic spread

19

2. Bone and joint

3 years after infection

younger age

3. Renal, skin

5 years after infection

first 5 years : rare

10 years : often

Hematogenic spread

20

Regional Lymphnodes

Complications are more common (than primary focus)

Compliactions occur within first 9 months after infection:

1. Disrupted abscess

2. Endobronchitis with :

a. Incomplete bronchial obstruction

b. Complete bronchial obstruction

21

c. Segmental lesions :

d. permanent changes (common):

Bronchial stricture

Bronchiectasis

Lung fibrosis

e. Bronchopneumonia :

Immunity

Bacteria

22

1. History

2. Contact /sources

3. Tuberculin Test (Mantoux)

4. Physic Diagnostic

5. X – ray

6. AFB /Hystopathology

Diagnosis TBC in children

23

Algorithm for Early Detection and Referral for Childhood Tuberculosis in Indonesia

Suspected TB: Close contact with adult with AFB sputum (+) Early reaction of BCG (in 3-7 days) Weight loss with no apparent cause, or underweight with no

improvement in 1 month with adequate nutritional support (failure to thrive)

Prolonged /recurrent fever with no apparent cause Cough more than 3 weeks Specific enlargement of superficial lymph node Scrofuloderma Phlychten conjunctivitis Tuberculin test positive (> 10 mm) Radiological findings suggestive TB

If > 3 positive Next page

24

Considered TB

Give anti-TB therapyObservation in 2 months

Clinical response (+) No clinical response/worsening

TB

Continue anti-TB therapy

Not TB MDR TB

Refer to hospital

Reevaluation in Referral Hospital:• Clinical signs• Tuberculin test• Radiological findings• Microbiology and serology examination• Histopatology examination• Diagnostic procedure and therapy according to

each hospital’s protocol

ATTENTIONPresence of any dangerous signs:• Seizure• Decreased level of consciousness• Neck stiffnessOr signs such as:• Spinal tumor/lump• Limping • Dam board phenomenon Refer to hospital

UKK Pulmonologi –IDAI. Jakarta;2002.

25

Source of infection:Difficult

Important:

Diagnosis

Therapy

History : Chronic Fever

Chronic cough

Body Weight

Malaise

Activity

26

Primary TB : asymptomatic

Respiratory symptoms /Rö ~ other infection

Conjunctivitis phlyctenularis

extrathoracal TB

Scrofuloderma

Lymphnode enlargement

Serous meningitis

Cold absces

Bone /joint TB

search

Physic Diagnostic

27

Important role in diagnosticAgents :

OT 0,9 mg PPD RT-23 2 TU / PPD S 5 TU

Intra-cutaneusly, antebrachii volar areaIntepretation: 48-72 h after injectionTransversal diameter of induration, ≠ erythema

TUBERCULIN TEST

28

TST interpretation

0-4 mm NEGATIV

E

5-9 mm DOUBTFUL

> 10 mm POSITIVE

No clinical infection

Current / past clinical infection

No need to repeat the test, unless strong suspicion of TB

- Technical error- Clinical infection- Cross reaction to BCG vaccine

Active, if :

< 6 ysTx (-)BCG (-)

Conversion :(-) (+)1 yearTx (-) , BCG (-)

Clinical infection

Cross reaction to BCG vacc

probableTB

> 10 mm Same result Same result + other signs

Repeated with same dose

29

False

Incubation : 2 – 10 mggSevere TB : miliary/meningitisSevere MalnutritionDehydrationDiseases with high feverTx. Corticosteroid / immunosupresiveCertain infections :

Morbili (or its vaccination) : 10 ds – 6 wksRubella : 1 – 3 wksPertussisHIV

Post BCG vaccination

Mycobacterium atypis

Morbus Hansen

Positive :

Negative :

30

Notifications:

I. Tuberculin Test (Mantoux)

Should be routinally started at 6 – 8 mos every year

if contact (+) and TST (-) repeat after 10 wks

still in close TST each 3 mos

Interpretation of TST post BCG

difficult

Induration varies : 0 – 20 mm

Kendig 1972 : susp. active infection if 15 mm

Lotte 1971 : active infection if: pre /post BCG 18 mm

31

II. BCG Scar (+)

not exclude the disease active infection

when BCG vaccination :

Within incubation period

Active TB already

Infected during incubation of BCG

Not effective vaccine

Notifications:

32

Not specificNormal chest X ray : not excluding the processDIAGNOSIS CAN NOT BE ACHIEVED BASE ON CHEST X RAY

Strongly suggestive TB: miliary paratracheal lymphnode enlargement

CHEST X RAY

33

Parameter 0 1 2 3Kontak TB tidak jelas laporan keluarga,

BTA (-) / tidak tahu /BTA tidak jelas

BTA (+)

Uji tuberkulin negatif Positif (≥ 10 mm, atau ≥ 5 mm pada keadaan imunosupresi)

Berat badan / keadaan gizi

BB/TB<90% atau BB/U<80%

klinis gizi buruk atau BB/TB <70% atau BB/U <60%)

Demam tanpa sebab jelas

> 2 minggu

Batuk lama ≥ 3 minggu Pembesaran kelenjar limfe koli, aksila, inguinal

>1 cm, jumlah >1, tidak nyeri

Pembengkakan tulang / sendi panggul, lutut, falang

Ada pembengkakan

Foto rontgen toraks normal / tidak jelas

Suggestive TB

Diagnostic scoring TB in children

34

Note :• Diagnosis using scoring system performend by a doctor• If scrofuloderma is present diagnose Tuberculosis• Body weight assessed at the time of admission (moment opname)• Fever /cough which not respond to standard therapy• Chest x ray is not main diagnostic tool in childhood TB• Children with rapid BCG reaction shoud be evaluated using

scoring system• diagnosis TB when the score > 6, (max 14)

35

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

36

Hospitalization

1. Ascertain diagnosis: repeated AFB, biopsy

2. Initial treatment in : severeTB /life threatening /infants

3. Corticosteroid /surgical treatment

4. Severe adverse reaction to TB regiment

5. Treatment for concomitant disease

6. Initial treatment for children whose parents /environments are not adequate

37

TB bacilli population

Location cavity,extra cell

intra macrophage

caseous mass

TB population A B CTB amount 107 - 109 105 - 106 103 – 104

metabolism & replication

active / rapidly

slowly sporadic / intermittent

acidity (pH) neutral / base

acid neutral

most effective drug (consc’ly)

INH, RIF,ETB

PZA, RIF, INH RIF, INH

38

TB drugs & pharmaceutical formulation

Isoniazid (H)

Rifampicin (R)

Pyrazinamide (Z)

Ethambutol (E)

monosubstance

combi-packs

fixed dose comb

39

FDC (Fixed Dose Combination) tablet formulation

WHO H : 30 mg R : 60 mg Z : 150 mg

IDAI H : 50 mg R : 75 mg Z : 150 mg

40

Drugs Daily dose(mg/Kg/day) Adverse reactions

2 Time/weekdose

(mg/Kg/dose))Isoniazid(INH)

5-15(300 mg))

Hepatitis, peripheral neuritis,hypersensitivity

15-40(900 mg))

Rifampicin(RIF)

10-15(600 mg))

Gastrointestinal upset,skin reaction, hepatitis, thrombocytopenia,

hepatic enzymes, including orangediscolouraution of secretions

10-20(600 mg)

Pyrazinamide(PZA)

15 - 40(2 g)

Hepatotoxicity, hyperuricamia,arthralgia, gastrointestinal upset

50-70(4 g)

Ethambutol(EMB)

15-25(2,5 g)

Optic neuritis, decreased visualacuity, decreased red-green colour

discrimination, hypersensitivity,gastrointestinal upset

50(2,5 g)

Streptomycin(SM)

15 - 40(1 g)

Ototoxicity nephrotoxicity25-40(1,5 g)

When INH and RIF are used concurrently, the daily doses of the drugs are reduced

National consensus of tuberculosis in children, 2001

Dosage of antituberculosis drug

41

TB therapy regimen

2 mo 6 mo 9 mo 12mo

INHRIFPZA

ETBSM

PREDDOT.S !

42

Therapy problem solutions

DOTS : Directly Observe Treatment Short-course

FDC : Fixed Dose Combination i.e. >2 drugs in one tablet / capsule in a fixed dose formulation

43

Corticosteroid

Meningitis

Serositis (pleura, pericard, peritoneal)

Endotracheal

Miliary

44

STOP therapy

Regular treatment : 6 bln – 1 ½ th

improvement, BW , fever (-)

Chest x ray improvement

ESR, if previous ESR

Source of infection (-)

If source (+) : continue with IPT (INH prophylaxis

treatment)

45

Side EffectsStreptomycin : 20 mg/kgBW/day

Nefrotoxic : rareN. VIII disturbance (mainly vestibular nerve)

AtaxiaVertigo

rare : deafnessPyrazinamide : 30 – 40 mg/kgBW/day

Hepatotoxic

46

INH : 10 – 20 mg/kgBW/day – 1 ddPeriferal neuritis : rare

due to B6 defisiensiHepatotoxic : previous liver disorder

other hepatotoxic drug : rifampicinOther : GI irritability

hypersensitive reaction neurology : psichosis seizure confusion

47

ETB : 15 – 20 mg/kgBW/day – 1 DD

Reversible occular complications

Blurred

Color blindness

Narrowed visual field

48

Rifampicin : 15 – 20 mg/kgBW/day – 1ddOrange discoloration : saliva, tear, conjunctivaGI. SymptomHepatotoxicTrombocytopenia – leukopenia“Influenza syndrome”FeverheadacheMalaise“Respiratory syndrome”Tightness Wheezing

49

INH Prophylaxis

TST (-) 3 mos

TST (+) 1 y

1. Infection prophylaxis

Single treatment : 5-10 mg/kgBW/day

Healthy childExposed to adult with AFB (+)

50

2.1. latent TB:

TST (+), BCG (-), Tx (-), < 6 y, healthy

conversion (+), BCG (-), Tx (-)

duration : 1 year

2.2. prevent exacerbation:

healed morbili, pertussis

Narcose

Tx. Corticosteroid

duration : 6 wks

2. Disease prophylaxisprevent the disease (current /past TB infection):

51

Advantage of INH prophylaxisProven to be effectiveNot interupt TST result if infection (+)

Disadvantage of INH prophylaxisNon complience in prophylactic medicationPharmacologic effect on neonates : data

52

PREVENTIONINH prophylaxis

Avoid contact active TB

BCG

Infants of mother with active TB

50% disease within 1 year

Prophylaxis is important!!

INH

BCG ?

53

Advantage of BCG Effective, one dose

Toksisitoxicity (-)

no need long term follow-up

Disadvantage of BCG

Individual response varies

interupt TST test result

need isolation/weaned until TST (+) (2 months)