Diagnosis TBC In Children

HMS Chandra Kusuma

Pediatric Departement Of Fac. Med. Brawijaya Univ. Saiful Anwar General Hospital

Clinical setting management

Suspect TB prove TB infection Diagnosis TB therapy Mantoux tuberculin skin test positive complete d: Ro, lab negative not TB Seek other etiologies

Clinical

Clinical types of pediatric TB nd

Pulmonary:

Infection (2 class): TST (+), clinical (-), radiographic (-) Disease (3rd class):
primary pulmonary TB milliary TB pleuritis TB progr primary pulm TB: pneumonia, endobr TB lymph nodes brain & meninges bone & joint gastrointestinal other organs

Extrapulmonary:

Clinical manifestation
vary, wide spectrum factors:
TB bacilli: numbers, virulence host: age, immune state

clinical manifestation
general manifestation organ specific manifestation

General manifestation
chronic fever, subfebrile anorexia weight loss malnutrition malaise chronic recurrent cough, think asthma! chronic recurrent diarrhea others

Organ specific
Respiratory Neurology : cough, wheezing, dyspnea : convulsion, neck stiffness, SOL manifestation Orthopedic : gibbus, crippled Lymph node : enlarge, scrofuloderma Gastrointestinal: chronic diarrhea Others

Complications of focus 1. Effusion 2. Cavitation 3. Coin shadow

Complications of nodes 1. Extension to bronchus 2. Consolidation 3. Hyperinflation

MENINGITIS OR MILIARY in 4% of children infected under 5 years of age

Most children become tuberculin sensitive

Uncommon under 5 years of age 25% of cases within 3 months 75% of cases within 6 months

LATE COMPLICATIONS Renal & Skin Most after 5 years

BRONCHIAL EROSION 3-9 months

A minority of children experience : 1. Febrile illness 2. Erythema Nodosum 3. Phlyctenular Conjunctivitis

PRIMARY COMPLEX Progressive Healing Most cases

Incidence decreases As age increased

3
Resistance reduced : 1. Early infection (esp. in first year) 2. Malnutrition 3. Repeated infections : measles, whooping cough streptococcal infections 4. Steroid therapy

BONE LESION Most within 3 years

infection

4-8 weeks

3-4 weeks fever of onset

12 months

24 months

Development Of Complex GREATEST RISK OF LOCAL & DISEMINATED LESIONS

DIMINISHING RISK
But still possible 90% in first 2 years

Miller FJW. Tuberculosis in children, 1982

Tuberculin skin test

Tuberculin test
TB infection cellular immunity delayed type hypersensitivity

tuberculin reaction

Tuberculin
Strength first intermediate
(standard dose)

PPD S Seibert 1 TU 5-10 TU 250 TU

PPD RT23 1 TU 2-5 TU 100 TU

second

Tuberculin delivery
1. Mantoux : intradermal injection 2. Multiple puncture :
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 report : in millimeter, even 0 mm Induration diameter : 0 - 5 mm : negative 5 - 9 mm : doubt > 10 mm : positive

Mantoux tuberculi n skin test

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

Tuberculin negative 1. No TB infection 2. Anergy 3. Incubation period

Anergy
Patient 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, ...

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 radiological manifestation

TB classification
modified)
Class

(ATS/CDC

Treatmen Contact Infection Disease t

0 1 2 3

+ + +

+ +

proph I proph II? therapy

Microbiology

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

Polymerase chain reaction

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.

Radiology

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

Radiographic picture
primary complex: lymph node enlargement milliary atelectasis cavity tuberculoma pneumonia air trapping - hyperinflation pleural effusion honeycombs bronchiectasis calcification, fibrosis

Radiographic picture
do not always help, particularly in small children at 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

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

Radiographic picture
Commonly found: enlargement of hilar/ paratracheal nodes sometimes difficult to interpret requires thorax CT with contrast Thorax CT reveals enlargement of lymph node in 60% children with TB infection and normal Chest rntgenogram
Delacourt C et.al. Arch Dis Child 1993;69:430-2.

Over diagnosis TB by CXR

100 80 60 40 20 0 Diagnosed by Xray alone Actual cases
100

Overdiagnosis
32

Serology

Serology
Sensitivity: 19 68% Specificity: 40 98%
Depends on: Type of antigen used Type of infection

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 .

Interferon
Detection of interferon- (QuantiFERON TB)

comparable with TST to detect latent TB infection Advantages - less affected by BCG vaccination - 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

The main problems

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

Diagnosis
1. 2. 3. 4. 5. 6. 7. 8. Clinical manifestation Tuberculin skin test Chest X ray Microbiology Pathology Hematology Known infection source Others : serologic, lung function, bronchoscopy

Clinical setting management

Suspect TB prove TB infection Diagnosis TB therapy Mantoux tuberculin skin test positive complete d: Ro, lab negative not TB Seek other etiologies

Practical clinical approach to Ped TB Scoring system

Stegen, 1969 Smith, Marquis, 1981 Migliori dkk, 1992 WHO, 1994

Algorithm
IDAI: 1998, 2002

Algorithm for Early Detection and Referral for

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

Childhood Tuberculosis in Indonesia

If > 3 positive

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Considered TB Give anti-TB therapy Observation in 2 months Clinical response (+) TB Continue anti-TB therapy
ATTENTION Presence of any dangerous signs: Seizure Decreased level of consciousness Neck stiffness Or signs such as: Spinal tumor/lump Limping Dam board phenomenon Send to hospital

No clinical response/worsening 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 hospitals protocol
UKK Pulmonologi IDAI.

Encountered problem
Increasing demands of TB drugs for Pediatric TB Increasing diagnosis of Pediatric TB using the IDAI algorhitm Over diagnosis !? Need improvement IDAI scoring system

Proposed IDAI scoring system

Feature
Contact TST BW (KMS)

0
not clear -

1
reported, AFB(-) <red line, BW unexplained >3weeks >1 node, >1cm,painle ss swelling sugestive

2
severe malnutritio n -

3
AFB(+ ) positiv e -

Score

Fever Cough Node enlargemn t Bone,joint CXR

<3week s -

normal

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 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 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

Thank you