TB Mngm 2 - Diagnosis

8/13/2019 TB Mngm 2 - Diagnosis

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Diagnosis (Part 2)

Pediatric TB Management Training

Respirology Coordination Working Unit



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Clinical setting management

Suspect TB

prove TBinfection

Mantoux tuberculinskin test

positive negative

not TB

Seek other

etiologies

completed:Ro, lab

Diagnosis TB

therapy



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Clinical



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Clinical types of pediatric TB• Infection (2nd class): TST (+), clinical (-),

radiographic (-)• Disease (3rd class):

– 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



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Clinical manifestation

• vary, wide spectrum

• factors:

– TB bacilli: numbers, virulence

– host: age, immune state

• clinical manifestation

– general manifestation

– organ specific manifestation



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General manifestation

• chronic fever, subfebrile

• anorexia

• weight loss

• malnutrition

• malaise

• chronic recurrent cough, think asthma!• chronic recurrent diarrhea

• others



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Organ specific

• Respiratory : cough, wheezing, dyspnea

• Neurology : convulsion, neck stiffness,

SOL manifestation• Orthopedic : gibbus, crippled

• Lymph node : enlarge, scrofuloderma

• Gastrointestinal: chronic diarrhea

• Others



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1/20/2014 15Miller FJW. Tuberculosis in children, 1982

A minority of children

experience :

1. Febrile illness

2. Erythema Nodosum

3. Phlyctenular Conjunctivitis

Complications of focus

1. Effusion

2. Cavitation

3. Coin shadow

Complications of nodes

1. Extension to bronchus2. Consolidation

3. HyperinflationMENINGITIS OR MILIARY

in 4% of children infected

under 5 years of ageLATE COMPLICATIONS

Renal & Skin

Most after 5 years

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

BRONCHIAL EROSION

Most children

become tuberculin

sensitive

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 COMPLEX

Progressive Healing

Most cases

Uncommon under 5 years of age

25% of cases within 3 months

75% of cases within 6 months

3-9 monthsIncidence decreases

As age increased



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Tuberculin skin test



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Tuberculin test

TB infection

cellular immunity

delayed type hypersensitivity

tuberculin reaction



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Tuberculin delivery

1. Mantoux : intradermal injection

2. Multiple puncture :• Heaf, special apparatus with 6 needles

• Tine, disposable, 4 needles

3. Patch test



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Tuberculin

Mantoux 0.1 ml PPD intermediate strengthlocation : volar lower arm

reading time : 48-72 h post injection

measurement : palpation, marked, measurereport : in millimeter, even ‘0 mm’

Induration diameter :

0 - 5 mm : negative

5 - 9 mm : doubt

> 10 mm : positive



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Mantoux

tuberculinskin 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 disease, post therapy

2. BCG immunization

3. Infection of Mycobacterium atypic



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Tuberculin negative

1. No TB infection

2. Anergy3. Incubation period



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AnergyPatient 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

• Certain viral infection: morbili, varicella

• Severe bacterial infection: typhus abdominalis,

diphteria, pertussis• Viral vaccination: morbili, polio

• Malignancy: Hodgkin, leukemia, ...



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TB infection & TB disease

• TB infection: CMI can control infection

– primary complex (+)

– cell mediated immunity (+)

– tuberculin sensitivity (DTH) (+)

– limited amount of TB bacilli

– no clinical or radiological manifestation

• TB disease: CMI failed to control TB infection TB infection + clinical and/or radiologicalmanifestation



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TB classification (ATS/CDC modified)

Class Contact Infection Disease Treatment

0 - - - -

1 + - - proph I

2 + + - proph II?

3 + + + therapy



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Microbiology



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Microbiology

• culture (Lowenstein Jensen)

• confirm the diagnosis

• negative result do not rule out TB

• positive result : 10 - 62 % (old method)

• methods: – old method

– radiometric (Bactec)

– PCR



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Polymerase chain reaction from gastric aspirate diagnosis of TB in children

Sensitivity: 44 – 90%

Specificity: 94 – 96,8%

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.



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Imaging diagnostic

• routine : chest X ray

• on indication : bone, joint, abdomen

• majority of CXR non suggestive TB

• pitfall in TB diagnostic



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Radiographic picture

• primary complex: lymph node enlargement

• milliary

• atelectasis

• cavity• tuberculoma

• pneumonia

• air trapping - hyperinflation

• pleural effusion

• honeycombs – bronchiectasis

• calcification, fibrosis



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

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

more confusingsuperadded bacterial pneumonia

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




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• 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

• 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.




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

Thorax CT reveals enlargement of lymph nodein 60% children with TB infection and normalChest röntgenogram

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




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100

32

0

20

40

60

80

100

Diagnosed by X-

ray alone

Actual cases

Over diagnosis TB by CXR

Over-diagnosis



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Serology



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Sensitivity: 19 – 68%

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

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

Depends on:Type of antigen used

Type of infection

Serology



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• 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 nontuberculousmycobacteria

- avoids variability and subjectivity associated withplacing and reading TST

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

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

Interferon γ



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Diagnosis



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Diagnosis

1. Clinical manifestation2. Tuberculin skin test

3. Chest X ray

4. Microbiology5. Pathology

6. Hematology

7. Known infection source8. Others : serologic, lung function,

bronchoscopy



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Clinical setting management

Suspect TB

prove TBinfection

Mantoux tuberculinskin test

positive negative

not TB

Seek otheretiologies

completed:Ro, lab

Diagnosis TB

therapy



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Practical clinical approach to Ped TB

• Scoring system

Stegen, 1969

Smith, Marquis, 1981

Migliori dkk, 1992

WHO, 1994

• AlgorithmIDAI: 1998, 2002



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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• Flychten conjunctivitis• Tuberculin test positive (> 10 mm)

• Radiological findings suggestive TB

If > 3 positive Next page

Considered TB



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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 therapyaccording 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.



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Encountered problem

• Increasing demands of TB drugs

for Pediatric TB

• Increasing diagnosis of PediatricTB using the IDAI algorhitm

• Over diagnosis !?

• Need improvement IDAI scoringsystem



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Proposed IDAI scoring system

Feature 0 1 2 3 ScoreContact not clear reported,

AFB(-)- AFB(+)

TST - - - positive

BW (KMS) - <red line,

BW

severe

malnutrition

-

Fever - unexplained - -

Cough <3weeks >3weeks - -

Nodeenlargemnt

- >1 node,>1cm,painless

- -

Bone,joint - swelling - -

CXR normal sugestive - -



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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 evaluatedwith scoring system

• TB diagnosis total score >5

• Score 4 in under5 child or strong suspicion, referto hospital

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



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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, beforemaking the diagnosis

Anthony Harries & Dermot Maher, 1997



Thank you

TB Mngm 2 - Diagnosis

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