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Tuberculosis in children
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
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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
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Mycobacterium tuberculosisMycobacterium tuberculosis colonycolony
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M.Tb cell wall stucture
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Pathogenesis of TB
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Mechanism of T cell activation Killing of M.Tb bacteria
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Granuloma formation
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Granuloma (Tubercle)
replication of bacteriaThe process is confined
Characteristic feature of TB :Caseating centreExtracellular bacteriaCells :
macrophageEpiteloid cellsT cellsGiant cells of Langhans
Central for protection
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Pathogenesis of TB infection
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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
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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
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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
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AGE-SPECIFIC RISK TO PROGRESS TO DISEASE AFTER PRIMARY INFECTION WITH Mycobacterium tuberculosisIN IMMUNOCOMPETENT CHILDREN
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primary focus
regional lymphadenitis
hematogenic spread
Time table
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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
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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
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1. Miliary dan meningitis TB
Within 1st year after infection
More common in younger age
Decreased immunity :MalnutritionHIV infection MeaslesPertussisStreptococcus infection
Hematogenic spread
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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
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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
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c. Segmental lesions :
d. permanent changes (common):
Bronchial stricture
Bronchiectasis
Lung fibrosis
e. Bronchopneumonia :
Immunity
Bacteria
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1. History
2. Contact /sources
3. Tuberculin Test (Mantoux)
4. Physic Diagnostic
5. X – ray
6. AFB /Hystopathology
Diagnosis TBC in children
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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
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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.
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Source of infection:Difficult
Important:
Diagnosis
Therapy
History : Chronic Fever
Chronic cough
Body Weight
Malaise
Activity
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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
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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
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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
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FalseFalse
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 :Negative :
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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
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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:
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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
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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
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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)
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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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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
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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
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TB drugs & pharmaceutical formulation
Isoniazid (H)
Rifampicin (R)
Pyrazinamide (Z)
Ethambutol (E)
monosubstance
combi-packs
fixed dose comb
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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
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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
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TB therapy regimen
2 mo 6 mo 9 mo 12mo
INHRIFPZA
ETBSM
PREDDOT.S !
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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
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Corticosteroid
Meningitis
Serositis (pleura, pericard, peritoneal)
Endotracheal
Miliary
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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)
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Side EffectsStreptomycin : 20 mg/kgBW/day
Nefrotoxic : rareN. VIII disturbance (mainly vestibular nerve)
AtaxiaVertigo
rare : deafnessPyrazinamide : 30 – 40 mg/kgBW/day
Hepatotoxic
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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
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ETB : 15 – 20 mg/kgBW/day – 1 DD
Reversible occular complications
Blurred
Color blindness
Narrowed visual field
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Rifampicin : 15 – 20 mg/kgBW/day – 1ddOrange discoloration : saliva, tear, conjunctivaGI. SymptomHepatotoxicTrombocytopenia – leukopenia“Influenza syndrome”FeverheadacheMalaise“Respiratory syndrome”Tightness Wheezing
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INH Prophylaxis
TST (-) 3 mos
TST (+) 1 y
1. Infection prophylaxis
Single treatment : 5-10 mg/kgBW/day
Healthy childExposed to adult with AFB (+)
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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):
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Advantage of INH prophylaxisProven to be effectiveNot interupt TST result if infection (+)
Disadvantage of INH prophylaxisNon complience in prophylactic medicationPharmacologic effect on neonates : data
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PREVENTIONINH prophylaxis
Avoid contact active TB
BCG
Infants of mother with active TB
50% disease within 1 year
Prophylaxis is important!!
INH
BCG ?
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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)