Download Diagnosis of Pediatric TB

Diagnosis of Pediatric TB
DR. PRAKASH SALDANHA
PROFESSOR & HOD PEDIATRICS
YENEPOYA MEDICAL COLLEGE
DIAGNOSIS OF PEDIATRIC TB
OBJECTIVES
1. MAGNITUDE OF THE PROBLEM
2. CLINICAL SPECTRUM OF TB IN CHILDREN
3. DIAGNOSTIC MODALITIES
4. UPDATED RNTCP GUIDELINES
5. FUTURE PRIORITIES
DIAGNOSIS OF PEDIATRIC TB
MAGNITUDE OF THE PROBLEM
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EMERGING HEALTH CRISIS
‘ TICKING BOMB ‘
Scarce information
Incidence , prevalence and mortality
Gross underestimates
Reports only smear positive cases .
DIAGNOSIS OF PEDIATRIC TB
MAGNITUDE OF THE PROBLEM
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EPIDEMIOLOGY
9 million people worldwide develop TB per year.
1 million children (<15 yrs) – 11%
3.4 million children in India have TB
94 million are at risk – 40 % (6 yrs); 80% (16 yrs)
10-15 % develop disease after infection
5-10 % childhood mortality is related to TB
10,000-20,000 children per year in India might be
acquiring MDR-TB
DIAGNOSIS OF PEDIATRIC TB
MAGNITUDE OF THE PROBLEM
WHY? - Increasing no. of children being
infected by MTB.
“ Wherever there are infected TB adults, there are infected
children. Nobody is immune ” …by Edith Lincoln – Pioneer in TB
50 yrs ago.
• Failure to control and treat infectious adult TB
• Rise in incidence of adult TB ( MDR/ XDR)
due to HIV outbreak
• Diagnosis of TB has been neglected for several
years due to difficulty in isolation of MTB.
DIAGNOSIS OF PEDIATRIC TB
MAGNITUDE OF THE PROBLEM
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CHALLENGES IN DIAGNOSIS
Demonstration of AFB for confirmation
Lack of correlation between clinical criteria ,
Mantoux test and radiology .
Selecting and interpretation of insensitive
diagnostic aids.
Recognising multiple clinical forms in children
( Tracing adult contacts, suspect risk factors, awareness of
asymptomatic presentation and nonspecific signs and symptoms ,
recognising typical clinical forms )
DIAGNOSIS OF PEDIATRIC TB
CLINICAL SPECTRUM
MULTIPLE CLINICAL FORMS
PULMONARY / EXTRAPULMONARY :
1) PRIMARY COMPLEX
2) PROGRESSIVE PRIMARY COMPLEX
LOCAL
HEMATOGENOUS
PARENCHYMAL
LYMPH NODE
MILIARY
DISSEMINATED
3) CHRONIC ADULTS FORMS
FIBROCAVITY /FIBROCASEOUS
CONGENITAL TB , INTESTINAL TB, SKIN ANDTONSILS
DIAGNOSIS OF PEDIATRIC TB
CLINICAL SPECTRUM
ATYPICAL FORMS
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ERYTHEMA NODOSUM
PHLYCTENULAR CONJUNCTIVITIS
CHOROID TUBERCLES
HEMATOLOGICAL – AIHA
CSOM
PERICARDITIS
CEMENT KIDNEY
IVC – THROMBOSIS
DIAGNOSIS OF PEDIATRIC TB
CLINICAL SPECTRUM
DIAGNOSIS - ? SUSPECT
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FEVER > 2 WEEKS – Documented , any type
COUGH > 2 WEEKS – Persistent , dry/moist
LOSS OF WEIGHT / NO WEIGHT GAIN -90 days, 5%
POSITIVE CONTACT WITH ACTIVE TB CASE
PRESENCE OF RISK FACTORS
( <1 yr, PEM, immunodeficient, h/o measles/pertusis,steroid RX, mother of NB with TB. )
• TYPICAL CLINICAL PRESENTATION
( TBM, Lymph node, pneumonia, hepatosplenomegaly )
• UNRESOLVING CLINICAL PICTURE
( pneumonia , lymph node , meningitis )
DIAGNOSIS OF PEDIATRIC TB
CLINICAL SPECTRUM
PITFALLS
ASYMPTOMATIC
NONSPECIFIC SIGNS AND SYMPTOMS
Cough with wheeze – reactive airway disease
Erythema nodosum, phlyctenular conjunctivitis .
DOCUMENTATION OF FEVER
ATTEMPT TO TRACE CONTACT WITH TB
Clinically ignored , not uncommon for parents to deny, failure to screen
children in family with adult TB.
DIAGNOSIS OF TB NEVER BE MADE ON THE BASIS HISTORY AND
PHYSICAL EXAMINATION
CHOROID TUBERCLES
ERYTHEMA NODOSUM
PHLYCTENULAR CONJUNCTIVITIS
LUPUS VULGARIS
SCROFULODERMA
ENLARGED CERVICAL LYMPH
NODE WITH ULCERATION &
SINUS DISCHARGE
DACTYLITIS
MATTED CERVICAL LYMPH
NODES
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
METHODS
1) DEMONSTRATION OF MTB OR ITS COMPONENTS
– SMEAR POSITIVE
Body fluids – Sputum , GL, BAL, Pleural , Pericardial , CSF, FNA
Lymph node
2) DEMONSTRATION OF
HOST RESPONSE TO
EXPOSURE TO MTB
“CLINICIANS MUST GET USED TO PROVE DIAGNOSIS AT ALL LEVELS BY
APPROPRIATE BACTERIOLOGICAL TEST”
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
METHODS
DEMONSTRATION OF MTB OR ITS COMPONENTS
1) ZIEHL NELSON STAINING
2) SPECIAL STAINS – Flurochrome
3) CULTURE – LJ(conventional )
4)
BACTEC
SEPTICCheck AFB
MGIT
MODS
PCR – Real time ( Catridge based ) , XPert MTB/RIF, RFLP, DNA
sequencing , DNA Strip Assay , NAAT
5) HPLC & GLC
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
METHODS
HOST RESPONSE TO EXPOSURE TO MTB
IMMUNE BASED
• Fluid chemistry – ADA
• Antigen – Antibody Assay
38-kDa (IgG), LAM( LIPOARABINOMANNAN )LAM ELISA ( urine, sputum , serum )
• IGRA’s – QuantiFERON –TB Gold , ‘T’ SPOT
• SKIN TESTING – MANTOUX TEST
PATHOLOGY BASED
• IMAGING /RADIOLOGY /HISTOLOGY – TYPICAL
GRANULOMAS
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
BACTERIOLOGY
Smear positivity is 15 %- Paucibacillary, Extra PTB
33 % - Hilar Lymphnodes +
77% - Advanced cases
ZN stain positive – sample contains > 10000 bacilli/ml
Failure for sputum induction:decreases chance by 1/3
CULTURE
40% positivity even with newer methods- equal efficacy
Cost and Availability
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
MOLECULAR TECHNIQUES –PCR
Wide variability in sensitivity and specificity.
Cannot differentiate living from dead bacilli.
Positive even after successful treatment .
Positive in 95 -100 % (culture + );50 % (culture - ) .
False positive in 1-30% cases .
NO DECISION CAN BE MADE ONLY ON THE BASIS
OF PCR
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
SEROLOGY – ANTIGEN ANTIBODY ASSAY
Overlap in different stage of infection & disease.
No specific antigen /antibody to confirm natural
infection /active disease.
All tests vary widely and negative in paucibacillary
disease.
Poor sensitivity and specificity .
TIME TO EDUCATE AND BAN THE USE IN CLINICAL
PRACTICE
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
IGRA’s
Just sophisticated Montoux –not standardised ,expensive
Do not differentiate TB infection from disease.
Use in India need further evaluation because it holds promise
for future application
QuantiFERON becomes +ve before TST . May be useful in
starting early Rx .
Antigen is specific and not present in other mycobacteria.
Low prevalence countries to detect latent TB infection .
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
TUBERCULIN TEST
• Proper technique – experience , depth of inj.
• Cautious interpretation
- cutoff point ( 5,10, 14mm)
- measurement - observor dependent
(interobservor variation 4mm)
• Variable amount of antigen
- host immune response, different strengths of
Tuberculins by labs
• False positive /False negative
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
CHEST RADIOGRAPHY
• IDEAL TECHNIQUE- Difficult in children
Upright position (PA) , Inspiratory phase, optimum exposure,
well centred, preferable lateral view to locate hilar shadow .
• MISINTERPRETATION - Digital xray – Highly technician
dependent , Presence of thymus shadow, Prominent CC
junctions in rickets , DDx of lymphoma, Persistence of right
upper lobe lesions in infants for a long time .
• MISSING PATHOGNOMIC SIGNS – Hilar lymphnodes,
pneumonia with effusion, miliary , fibrocavity.
• NORMAL CHEST XRAY – 10 % in active TB disease.
• RADIATION EXPOSURE in children
• AVAILABILITY OF CT /MRI - Doubtful findings ,Neuroimaging
DIAGNOSIS OF PEDIATRIC TB
LAB DIAGNOSIS
PITFALLS
BCG TEST – NO ROLE
Many variables – high concentration of
tuberculin
Cannot differentiate natural vs vaccine induced
infection , active vs old healed disease.
DIAGNOSIS OF PEDIATRIC TB
CONSENSUS –GUIDELINES
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DEFINITIONS WERE REVISITED
RECOMMENDATIONS
STANDARD OPERATING PROCEDURES( SOP’s)
DIAGNOSTIC ALGORITHMS FOR PULMONARY
TB AND LYMPH NODE TB
DIAGNOSIS OF PEDIATRIC TB
CONSENSUS –GUIDELINES
DEFINITIONS - REVISITED
• Loss of weight /no weight gain
3 months, >5% body weight
• Highly suggestive chest X-ray
Hilar /paratracheal lymphadenitis, Parenchymal lesion with
effusion , Miliary TB , Fibrocavity
• Significant lymphadenopathy
> 2cm in one or more sites, matted,cold abscess with or
without discharging sinus
DIAGNOSIS OF PEDIATRIC TB
CONSENSUS –GUIDELINES
DEFINITIONS - REVISITED contd…
NEW CASE – No previous ATT or < 4 weeks
New smear +ve PTB, New smear –ve PTB, Extra PTB
PREVIOUSLY TREATED CASES
RELAPSE – evidence of recurrence after the child is cured/completed
ATT course.
TREATMENT AFTER DEFAULT – Active disease in patient who has taken
atleast 4 weeks of ATT and atleast interruption of 2 months
FAILURE TO RESPOND- failure to respond/ deteriorates
(bacteriological/clinical ) after 12 weeks of intensive phase of ATT.
RETREATMENT – OTHERS – All smear negative retreatmet cases do not fit
into the above definitions and the decision to treat again was taken on
clinical grounds .
DIAGNOSIS OF PEDIATRIC TB
CONSENSUS –GUIDELINES
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RECOMMENDATIONS
Demonstrate bacteriological evidence by sputum microscopy
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Alternative specimens ( GL, IS , BAL) should be collected if
sputum sample is not available or if sputum microscopy is
negative .
No role for serology , PCR and BCG test since they are
inaccurate/inconsistent/non validated
Current evidence does not support the routine use of IGRA’s
– needs further evaluation in India.
Clinical scoring is not validated .
Search for Extra PTB if chest X-ray is normal (CT/MRI)
DIAGNOSIS OF PEDIATRIC TB
CONSENSUS –GUIDELINES
STANDARD OPERATING PROCEDURES ( SOP’s)
1) TUBERCULIN TEST
Standard test – Mantoux
Optimal strength – 1, 2, 5 TU ( 2 TU preferable)
PPD – RT 23 or equivalent most suitable
Raised wheal 6mm , intradermal route
Read induration after 48-72 hrs in horizontal plane by
palpatory or ball point method
Cut off 10mm or more (up to 5 TU )
Reading may be done up to 7 days if reports late .
Repeat test in other if induration < 10 mm – clinical suspect.
DIAGNOSIS OF PEDIATRIC TB
CONSENSUS –GUIDELINES
STANDARD OPERATING PROCEDURES ( SOP’s)
2) BACTERIOLOGICAL INVESTIGATIONS USING ALTERNATIVE SPECIMENS
GASTRIC LAVAGE :
Early morning aspirate after 6 hrs overnight fasting
Appropriate size intragastric tube
15-30ml NS washing is taken as 2nd sample .
Contents transferred to the lab immediately
INDUCTION OF SPUTUM –PROVOKE COUGH :
3% nebulised hypertonic saline , pretreatment with nebulised salbutamol
prior to induction , chest physiotherapy after saline nebulisation ,
collect secretions from throat or nasopharynx using a collector attached
to a suction at one end and a catheter /tube to the other end
BAL :
Bronchoscopy if there is persistent pneumonia .
PEDIATRIC PULMONARY TB – DIAGNOSTIC
ALGORITHM –FLOW CHART
FEVER OR COUGH > 2 WEEKS AND/OR
LOSS OF WEIGHT /NO WEIGHT GAIN AND/OR
HISTORY OF CONTACT
SPUTUM EXAMINATION
NEGATIVE
RECEIVED ANTIBIOTIC COURSE
SICK CHILD
SEVERE RESPIRATORY DISTRESS
ANY OTHER REASON
EITHER OR BOTH
NEGATIVE
SMEAR
NEGATIVE
PTB Rx
POSITIVE
SMEAR +VE PTB
Rx AS PER
GUIDELINES
X RAY CHEST + TST
BOTH POSITIVE
SMEAR
NEGATIVE
GL/IS/BAL
SMEAR
POSITIVE
•NORMAL CHEST X-RAY
•TST NEGATIVE
REVIEW ALTERNATE DIAGNOSIS
LOOK FOR EXTRA PTB
(CTCHEST/OTHER INVESTIGATIONS )
•NORMAL CHEST XRAY
•TST POSITIVE
ALTERNATE DIAGNOSIS
EXPERT HELP
•CHEST X-RAY NONSPECIFIC SHADOWS
•TST +VE OR –VE
REPEAT CHEST X –RAY AFTER A COURSE
OF ANTIBIOTIC IF NOT RECEIVED
SMEAR +VE
TREAT AS PER GUIDELINES
PERSISTENCE OF NON SPECIFIC
SHADOWS
GL/BAL/IS
SMEAR NEGATIVE
LOOK FOR ALTERNATE
Dx
TREAT AS SMEAR NEGATIVE PTB
PEDIATRIC LYMPH NODE TB – DIAGNOSTIC
ALGORITHM –FLOW CHART
ENLARGED LYMPH NODE
MATTED ,COLD ABSCESS
DISCHARGING SINUS
LYMPH NODE > 2 CM ONE OR MORE SITE
COURSE OF ANTIBIOTIC
PUS/ASPIRATE (FNAC)
ZN STAIN + VE
GRANULOMATOUS
CHANGES
TREAT AS CASE
ZN STAIN –VE
NO GRANULOMATOUS
CHANGE
NO RESPONSE IN 2 WEEKS
LYMPH NODE BIOPSY
CONSIDER ALTERNATE Dx
ABDOMINAL TB
• No standard guidelines for sonography
diagnosis
• Suspect : Corroborative evidence (not specific
to TB alone )
Mesenteric lymph node > 15mm size
Thickened (echogenic ) mesentry or omentum
Dilated or matted bowel loops
Ascites +/- (exudate )
CONGENITAL TB
BEITZKE CRITERIA -1935
1. Bacteriological proof of TB by isolation of MTB
from infant
2. Primary complex in liver MASS AT PORTA
HEPATIS (liver biopsy )
OR : FOCI IN THE LUNG
HILAR LYMPH NODES
MEDIASTINAL LYMPH NODES
MESENTERIC LYMPH NODES
(Modified by MILLER )
DIAGNOSIS OF PEDIATRIC TB
FUTURE PRIORITIES
• Evaluate and validate the new diagnostic algorithm .
• Evaluate newer diagnostic tests in childhood TB
Eg: XPertRif , Urine LAM , MODS .
• Development of new diagnostic tests suitable for child
specimens – specially for latent TB.
• Standardization of Mantoux test.
• Evaluation of new skin test based on ESAT 6 antigen .
• Enhance district hospital facilities.
• Involvement of private sector.
• Record/ Report/Notify .
TAKE HOME MESSAGE
• SUSPECT TB IN CHILDREN ON CLINICAL GROUNDS
• DEMONSTRATE BACTERIOLOGICAL EVIDENCE TO CONFIRM
• SOP’s FOR ALTERNATIVE SPECIMENS ( GL,IS, BAL) & MANTOUX TEST
• DO NOT GET TEMPTED WITH NEWER DIAGNOSTIC MODALITIES
• USE CT/MRI –IF X-RAY IS NOT SUGGESTIVE OF TB OR TO LOOK FOR EXTRA
PTB
• FOLLOW GUIDELINES –WHICH ARE UPDATED REGULARLY
• RESEARCH – ‘GOLD STANDARD TEST ‘ IN CHILDREN