Pediatric Tuberculosis

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Definition

Tuberculosis is a disease due to Mycobacterium tuberculosisinfection with systemic spread thus

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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

Tuberculosis

The reaction of the tissues of the human host to the presence and multiplication of

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human host to the presence and multiplication of Mycobacterium tuberculosis or Mycobacterium bovis

History

• ancient Egypt : gibbus

• 1882, Koch, identification

• management : sanatorium, collapse treatment

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treatment

• Chemotherapy :– PAS – 1943 – Lehmann

– Streptomycine – 1945 - Waksman & Schats

– Isoniazid – 1952 – Domagk

– Rifampicine - 1957

Magnitude of problem

• TB one of the oldest diseases of human

• remains one of the deadliest diseases in the world

• 8 million of new cases yearly

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• 8 million of new cases yearly

• 3 million death yearly

• 20-40% population is infected

• reemergence, global emergency

The secret

Why TB is so strong and robust?

• the secret: specific characters of the bacilli

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• special issues:

hematogenic spread

infection vs disease

primary vs post-primary

The main problems

• Diagnosis

– Clinical manifestations : not specific �

both over/under diagnosis & over/under treatment

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– diagnostic specimen : difficult to obtain

– TB infection or TB disease ? � no

diagnostic tool to distinguish

• Adherence / compliance

– Drug discontinuation � treatment failure

Etiology

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Etiology

The bacilli• Mycobacterium tuberculosis• Mycobacterium bovis

features:

� slender, often slightly curved, rods

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� 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)

TB bacilli

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TB bacilli

M tuberculosisCharacteristics :

1. live in weeks in dry condition

2. no endotoxins, no exotoxins

3. hematogenic spread

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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

Transmission

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Transmission

Transmission ...

• airborne human to human transmission by droplet nuclei

• adult pulmonary TB: cough, sneeze, speak, or sing

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sing

• droplet nuclei : contain 2-3 bacilli, small size (1-5µ) keep in the air for long period

• inhalation, reach alveoli

• middle and lower lobes

TB droplet nuclei

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Transmission factors:

• doses / numbers

• concentration in the air

• virulence

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• virulence

• exposure duration

• host immune state

Infection source

• Known source of infection, has

diagnostic value

• Shaw (1954), level of infectiousness :

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• Shaw (1954), level of infectiousness :– AFB (+) : 62.5 %

– AFB (-), M tb (+) : 26.8 %

– AFB (-), M tb (-) : 17.6 %

Transmission rate (Shaw ’54)

adultTB patient

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AFB(+)AFB(-)

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

65% 26% 17%

Pathogenesis

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Pathogenesis

Location of primary focus

in 2,114 cases, 1909-1928

Location %Lung 95.93

Intestine 1.14

Skin 0.14

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Skin 0.14

Nose 0.09

Tonsil 0.09

Middle ear (Eustachian tube) 0.09

Parotid 0.05

Conjunctiva 0.05

Undetermined 2.41

droplet nuclei inhalation

alveoli ingestion by PAM’S

intracellular replicationof bacilli

destructionof bacillidestruction of PAM’S

Tubercle formation Hilar lymph nodesLymphogenic spread

primary focus lymphangitis lymphadenitis

9/20/2010 20Figure. Pathogenesis of primary tuberculosis

hematogenic spread

multiple organs remote focidisseminated primary TB

acute hematogenicspread

occult hematogenicspread

primary

complex

CMI

Incubation period

• first implantation � primary complex

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

• first weeks: logaritmic growth, : 103-10

4 �

elicit cellular response

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elicit cellular response

• end of incubation period:

– primary complex formation

– cell mediated immunity

– tuberculin sensitivity

�������� PrimaryTB infection has established

lymphadenitis

lymphangitis

Pathogenesis ...Pathogenesis ...

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primary focus

Hematogenous spread

• during incubation period, before TB infection establishment:

– lymphogenic spread

– hematogenic spread

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–hematogenic spread

• hematogenic spread (HS):

–occult HS

–acute generalized HS

Occult HS

• most common

• sporadic, small number

• no immediate clinical manifestation

• remote foci in almost every organ

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• remote foci in almost every organ

• rich vascularization: brain, liver, bones & joints, kidney

• including: lung – apex region

• CMI (+): silent foci - dormant, potential for reactivation

TB hematogenous spread

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Acute HS

• less common

• large number

• immediate clinical manifestation: disseminated TB

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disseminated TB

• milliary TB, meningitis TB

• tubercle in same size, special appearance in CXR

Miliary TB

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Miliary TB

Primary complex

• end of incubation period

• TB infection establishment

• tuberculin sensitivity (DTH)

• cell mediated immunity

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• cell mediated immunity

• end of hematogenic spread

• end of TB bacilli proliferation

• small amount, live dormant in granuloma

• new exogenous TB bacilli: destroyed / localized

Tuberculin skin test

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Tuberculin skin test

Tuberculin test

TB infection

cellular immunity

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delayed type hypersensitivity

tuberculin reaction

Tuberculin

StrengthPPD S

SeibertPPD RT23

first 1 TU 1 TU

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first 1 TU 1 TU

intermediate(standard dose)

5-10 TU 2-5 TU

second 250 TU 100 TU

Tuberculin delivery

1. Mantoux : intradermal injection

2. Multiple puncture :

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• Heaf, special apparatus with 6 needles

• Tine, disposable, 4 needles

3. Patch test

Tuberculin

Mantoux 0.1 ml PPD intermediate strength

location : volar lower arm

reading time : 48-72 h post injection

measurement : palpation, marked, measure

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report : in millimeter, even ‘0 mm’

Induration diameter :

� 0 - 5 mm : negative

� 5 - 9 mm : doubt

� > 10 mm : positive

Mantoux

tuberculin

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tuberculin

skin test

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Pengukuran Uji tuberkulin

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Tuberculin positive

1. TB infection :

� infection without disease / latent TB infection

� infection and disease

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� infection and disease

� disease, post therapy

2. BCG immunization

3. Infection of Mycobacterium atypic

AnergiPatient with primary complex do not give reaction to TST due to supression of CMI :

• Severe TB: miliary TB, TB meningitis

• Severe malnutrition

• Steroid, long term use

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• Steroid, long term use

• Certain viral infection: morbili, varicella

• Severe bacterial infection: typhus abdominalis, diphteria, pertussis

• Viral vaccination: morbili, polio

• Malignancy: Hodgkin, leukemia, ...

TB infection & TB disease

• TB infection: CMI can control infection

– primary complex

– tuberculin sensitivity (DTH)

– cell mediated immunity

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– cell mediated immunity

– no clinical or radiological manifestation

• TB disease: CMI failed to control TB infectionTB infection + clinical and/or radiological manifestation

TB classification (ATS/CDC modified)

Class Contact Infection Disease Manage ment

0 - - - -

1 - -

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1 + - - proph I

2 + + - proph II?

3 + + + therapy

TB Natural history overviewprimary TB infection

primary TB disease latent infection

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no diseasepost primary TB

respiratory TBnon respir TB

new infection

Pathology

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Pathology

Pathology

• complicated pathogenesis �varied pathology

�clinical manifestation

�radiologic appearance

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�radiologic appearance

• lung represent

• tubercle, granuloma, tuberculoma, fibrosis, fistula, cavity, atelectasis

• complication of primary focus: so many possibilities

Lesions of pulmonary TB

• Parenchym: primary focus, pneumonia, atelectasis, tuberculoma, cavitary

• Lymph node: hilar, paratracheal, mediastinal

• Airway: air trapping, endobronchial TB,

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• Airway: air trapping, endobronchial TB, bronchial stenosis, fistula, bronchiectasis

• Pleura: effusion, fistula, empyema, pneumothorax, hemothorax

• Blood vessels: milliary, hemorrhage

tubercle formationresolution

primary focus

PathologyPathology

remote focireg lymph node

milliary seed

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calcification

2nd lung lesions

caseation

liquefaction

granuloma

tuberculoma

cavity

erodes airway

compresses airway

rupt to pleura rupt to airway bronchiectasis

fibrosis

br pl fistula

Clinical

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Clinical

Clinical types of pediatric TB

• Infection: TST (+), clinical (-), radiographic (-)

• Disease:– Pulmonary:

• primary pulmonary TB

• milliary TB

• pleuritis TB

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• pleuritis TB

• progr primary pulm TB: pneumonia, endobr TB

– Extrapulmonary:• lymph nodes

• brain & meninges

• bone & joint

• gastrointestinal

• other organs

Clinical manifestation

• vary, wide spectrum

• factors:

– TB bacilli: numbers, virulence

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– TB bacilli: numbers, virulence

– host: age, immune state

• clinical manifestation

– general manifestation

– organ specific manifestation

General manifestation

• chronic fever, subfebrile

• anorexia

• weight loss

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• weight loss

• malnutrition

• malaise

• chronic recurrent cough, think asthma!

• chronic recurrent diarrhea

• others

Organ specific

• Respiratory : cough, wheezing, dyspnea

• Neurology : convulsion, neck stiffness,

SOL manifestation

• Orthopedic : gibbus, crippled

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• Orthopedic : gibbus, crippled

• Lymph node : enlarge, scrofuloderma

• Gastrointestinal: chronic diarrhea

• Others

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Complications of focus

1. Effusion

2. Cavitation

3. Coin shadow

Complications of nodes

1. Extension to bronchus

2. Consolidation

3. HyperinflationMENINGITIS OR MILIARY

in 4% of children infected

under 5 years of ageLATE COMPLICATIONS

Renal & SkinMost after 5 years

BRONCHIAL EROSION

Most children

become tuberculin

sensitive

3-9 months

9/20/2010 61Miller FJW. Tuberculosis in children, 1982

A minority of children

experience :

1. Febrile illness

2. Erythema Nodosum

3. Phlyctenular Conjunctivitis 1 2 3 4 5 6

BONE LESIONMost within

3 years

24 months

Resistance reduced :

1. Early infection

(esp. in first year)

2. Malnutrition

3. Repeated infections :

measles, whooping cough

streptococcal infections

4. Steroid therapy

infection

12 months

DIMINISHING RISK

But still possible

90% in first 2 yearsGREATEST RISK OF LOCAL & DISEMINATED LESIONS

Development Of Complex

4-8 weeks 3-4 weeks fever of onset

PRIMARY COMPLEXProgressive HealingMost cases

Uncommon under 5 years of age25% of cases within 3 months75% of cases within 6 months

3-9 monthsIncidence decreasesAs age increased

Pemeriksaan mikrobiologis

• Memastikan D/ TB

• Hasil negatif tidak menyingkirkan D/ TB

• Hasil positif : 10 - 62 % (cara lama)

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• Hasil positif : 10 - 62 % (cara lama)

• Cara :

– cara lama,

– radiometrik,

– PCR

Radiology, serology , ...

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Radiology, serology , ...

Imaging diagnostic

• routine : chest X ray

• on indication : bone, joint, abdomen

• majority of CXR non suggestive TB

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• majority of CXR non suggestive TB

• pitfall in TB diagnostic

Radiographic picture

• primary complex: lymph node enlargement

• milliary

• atelectasis

• cavity

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• cavity

• tuberculoma

• pneumonia

• air trapping - hyperinflation

• pleural effusion

• honeycombs – bronchiectasis

• calcification, fibrosis

do not always help, particularly in small childrenat times can be confusing

some cases: extensive disease from radiography � clinical exam revealed little or nothing

Radiographic picture

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� clinical exam revealed little or nothing

more confusing � superadded bacterial

pneumonia (+)

Osborne CM et.al. Arch Dis Child 1995;72:369-74

• No radiographic picture is typical of TB

• Many lung diseases have similar radiographic appearances mimicking PTB

• Cannot distinguish active pulmonary TB –inactive PTB – previously treated TB

Radiographic picture

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inactive PTB – previously treated TB

• May not detect early stages of TB disease– under-reading

– over-reading

– intra-individual inconsistency

Vijayan VK. Indian J Clin Biochem 2002;17(2):96-100.

Commonly found: enlargement of hilar/paratracheal nodes � sometimes difficult to interpret � requires thorax CT with contrast

Radiographic picture

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Thorax CT reveals enlargement of lymph node in 60% children with TB infection and normal Chest röntgenogram

Delacourt C et.al. Arch Dis Child 1993;69:430-2.

100

60

80

100

Over diagnosis TB by CXR

Over-diagnosis

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32

0

20

40

Diagnosed by X-

ray alone

Actual cases

Sensitivity: 19 – 68%

Specificity: 40 – 98%

Disadvantages

Depends on:Type of antigen usedType of infection

Serology

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Disadvantages

results affected by factors such as

- age

- history of BCG vaccination

- exposure to atypical Mycobacteria

- unable to differentiate between infection and disease

Khan EA and Starke JR. Emerg Infect Dis 1995;1:115-23.

Polymerase chain reaction

• PCRPCRPCRPCRfrom gastric aspirate ���� diagnosis of TB in children Sensitivity: 44 – 90%Specificity: 94 – 96,8%Compared to MTB culture

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Compared to MTB cultureLodha 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 MTBLodha R et.al. Indian J Pediatr 2004;71:221-7.

• Detection of interferon- γ (QuantiFERON-TB)

comparable with TST to detect latent TB infection

Advantages- less affected by BCG vaccination- can discriminates responses due to nontuberculous

Interferon γ

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- can discriminates responses due to nontuberculous mycobacteria

- avoids variability and subjectivity associated with placing and reading TST

The utility of QFT in predicting the progression to active TB has not been evaluated

Mazurek GH et.al. MMWR Dispatch 2002;51.

Diagnosis

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Diagnosis

Prognostic factors

A. TB bacilli :– virulence

– infection dose

B. Patient :– general condition

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– general condition

– age

– nutritional state

– coinfection: morbili, pertussis

– genetic

– stress; physically (trauma, surgery) or mentally

The main problems

• Diagnosis– Clinical manifestations : not specific �both over/under diagnosis & over/under treatment

– diagnostic specimen : difficult to obtain

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– 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

Diagnosis1. Tuberculin skin test

2. Chest X ray

3. Clinical manifestation

4. Microbiologic

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5. Pathology

6. Hematological

7. Known infection source

8. Others : serologic, lung function, bronchoscopy

Clinical setting management

Suspect TB

proveTB

Mantoux test

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proveTB infection positive negative

not TB

Seek other etiologies

completed: Ro, labDiagnosis TB

treatment

Practical clinical approach to Ped TB

• Scoring system

�Stegen, 1969

�Smith, Marquis, 1981

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�Migliori dkk, 1992

�WHO, 1994

• Algorithm

�IDAI, 1998, 2002

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

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• Cough more than 3 weeks• Specific enlargement of superficial lymph node• Scrofuloderma• Flychten conjunctivitis• Tuberculin test positive (> 10 mm)• Radiological findings suggestive TB

If > 3 positive Next page

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

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Continue anti-TB therapy Refer to hospital

Reevaluation in Referral Hospital:Clinical signsTuberculin testRadiological findingsMicrobiology and serology examinationHistopatology examinationDiagnostic 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 � Send to hospital UKK Pulmonologi –IDAI. Jakarta;2002.

Encountered problem

• Increasing demands of TB drugs for Pediatric TB

• Increasing diagnosis of Pediatric

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TB using the IDAI algorhitm

• Over diagnosis ?

• Need improvement � IDAI scoring system

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

-

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BW� malnutrition

Fever - unexplained - -

Cough <3weeks >3weeks - -

Node enlargemnt

- >1 node, >1cm,painless

- -

Bone,joint - swelling - -

CXR normal sugestive - -

Notes for IDAI scoring system• Diagnosis by doctor

• BW assessement at present

• Fever & cough no respons to standard tx

• CXR is NOT a main diagnostic tool in children

• All accelerated BCG reaction should be evaluated

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• All accelerated BCG reaction should be evaluated with scoring system

• TB diagnosis total score >5

• Score 4 in under5 child or strong suspicion, refer to hospital

• INH prophylaxis for AFB(+) contact with score <5

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

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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

Treatment

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Treatment

Objectives of treatment

• Rapid reduction of the number

of bacilli

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• Preventing acquired drug

resistance

• Sterilization to prevent relapses

Treatment principles

• Drug combination, not single drug

• Two phases :

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� Initial phase (2 months) – intensive, bactericidal effect

� Maintenance phase (4 months / more) – ‘sterilizing’ effect, prevent relaps

Smear +Culture +

108

107

106

105

Sensitive organisms Resistant organisms

Nu

mb

er

of

bacil

li p

er

ml

of

sp

utu

m

The ‘fall and rise’ phenomenon

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Smear -Culture +

Smear -Culture -

104

103

102

101

100

Start of treatment(isoniazid alone)

Weeks of treatment

0 3 6 9 12 15 18 WHO 78351

Nu

mb

er

of

bacil

li p

er

ml

of

sp

utu

m

Toman K, Tuberculosis, WHO, 1979

Treatment principles

• Long duration � problem of

adherence (compliance)

• Other aspects :

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• Other aspects :

�Nutrition improvement

� prevent / search & treat other disease

Hypothetical model of TB therapy

A

B

Pop A = rapidly multiplying (caseum)

Pop B = slowly multiplying (acidic)

Pop C = sporadically multiplying

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B

C

Bacteridal activity & ‘sterilizing’ effect

0 1 2 3 4 5 6

Pop C = sporadically multiplying

Months of therapy

DrugsDaily dose

(mg/Kg/day)Adverse reactions

2 Time/week

dose

(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)

Dosage of antituberculosis drug

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discolouraution of secretions

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 nephrotoxicity

25-40

(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

Populasi basil TB pada pasien

Kavitas,ekstrasel

Massa kijuDalam makrofag

(intrasel)

Jumlah populasi 107 - 109 104 - 105 104 - 105

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RIF, INH

Netral

Metabolisme danperkembang biak

AktifLambat atauintermiten

Lambat

pH Netral/basa Asam

Obat paling efektif(berturut-turut)

INH, RIF,STREP

PZA, RIF, INH

Drug activities upon TB pop

TB Population

Multiplying rate

Drug

activities

A rapidly INH>>SM>

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A rapidly INH>>SM>

RIF>EMB

B slowly PZA>>RIF>>

INH

C sporadically RIF>>INH

TB therapy regimen

2 mo 6 mo 9 mo 12mo

INHRIF

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RIFPZA

EMBSM

PREDDOT.S !

Corticosteroid

• Anti inflammation

• prednison : 1 - 3 mg/kg BB/hari, 3x/hari oral 2 - 4 minggu, tapering off

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tapering off

• Indications :

– TB milier

– Meningitis TB

– Pleuritis TB with effusion

Treatment evaluation

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

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especially in the first 2 month

• Main : clinical

• supporting exam as adjuvant

Treatment evaluation

• Clinical improvement :– Increased body weight

– Increased appetite

– Diminished / reduced symptoms (fever,

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– Diminished / reduced symptoms (fever, cough, etc)

• Supporting examination : – Chest X rays : 2 / 6 month (on indication)

– Blood : BSR

– Tuberculin test : once positive, do not needed to repeat !

Treatment failure

• Inadequate response, despite adequate therapy :

– Review the diagnosis, not a TB case ?

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– Review the diagnosis, not a TB case ?

– Review other aspects : nutrition, other

disease

– MDR – rarely in children

• Treatment discontinuation

Treatment problems

• The main : compliance / adherence

• The factors :

– Long duration

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– Drug side effect

– Initial improvement – misinterpreted by patients /

parents

– Inconvenient health service

– Socio-economic-cultural factors

• The following : drug resistance

DOTS with a SMILE

S : Supervised

M : Medication

S : Supervised

M : Medication

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I : In

L : a Loving

E : Environment

(Grange JM, Int J Tuberc Lung Dis 1999; 3:360-362)

I : In

L : a Loving

E : Environment

(Grange JM, Int J Tuberc Lung Dis 1999; 3:360-362)

Treament problem solution: FDC

Fixed dose combination: >2 drugs in one tablet in a fixed dose formulation

• simple dosing

• patient friendly, doctor friendly

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• patient friendly, doctor friendly

• increase adherence

• reduce MDR

• easier drug supplying

• easier drug monitoring

FDC tablet formulation

WHO

• H : 30 mg

• R : 60 mg

IDAI

• H : 50 mg

• R : 75 mg

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• R : 60 mg

• Z : 150 mg

• R : 75 mg

• Z : 150 mg

WHO FDC (H/R/Z:30/60/150 & H/R:30/60)

BW

(kg)

Intensive, 2 mo

(tablet)

Continuation, 4 mo

(tablet)

<7 1 1

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8-9 1,5 1,5

10-14 2 2

15-19 3 3

20-24 4 4

25-29 5 5

IDAI FDC (H/R/Z:50/75/150 & H/R:50/75)

BW

(kg)

Intensive, 2 mo

(tablet)

Continuation, 4 mo

(tablet)

5-9 1 1

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5-9 1 1

10-19 2 2

20-33 4 4

Note: BW < 5kg should be referred and need tailored dosing

WHO vs IDAI fdc formulation

• WHO:

– INH: 4-6 mg/kgBW

– BW grouping: too many

– not practical

– hard to remember

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– hard to remember

– a gap for BW 30-33 kg

• IDAI

– INH: 5-10 mg/kgBW

– simple BW grouping

– more friendly both for doctor and patient

TraceTraceTraceTrace

Adult TB patient centri-

fugal

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Child TBpatient

centri-petal

case finding

centripetal

• trace the source

• adult people

centrifugal

• trace other ‘victims’

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• adult people

• close contact

• by chest X ray

‘victims’

• children

• close contact

• by tuberculin

Pencegahan

• Perbaikan sosio ekonomi

• Kemoprofilaksis

• Imunisasi BCG

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• Imunisasi BCG

Kemoprofilaksis primer

• Mencegah infeksi

• Anak kontak dengan pasien TB aktif, tetapi

belum terinfeksi (uji tuberkulin negatif)

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• Obat : INH 5 - 10 mg/kg BB/hari

Kemoprofilaksis sekunder

Mencegah penyakit TB pada anak yang terinfeksi :

1. Mantoux (+), Rö (-), klinis (-) :• Umur < 5 th

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• 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

Imunisasi BCG

• Imunitas spesifik

• Uji tuberkulinmenjadi (+)

• Mt (-) baru BCG

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• Mt (-) baru BCG

• Masal : langsung BCG tanpa Mt

• Reaksi lokal : membantu screening

Thank you

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Thank you