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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 • • 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 • • • • • • 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 • • • • 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 • • • • • • • • ERYTHEMA NODOSUM PHLYCTENULAR CONJUNCTIVITIS CHOROID TUBERCLES HEMATOLOGICAL – AIHA CSOM PERICARDITIS CEMENT KIDNEY IVC – THROMBOSIS DIAGNOSIS OF PEDIATRIC TB CLINICAL SPECTRUM DIAGNOSIS - ? SUSPECT • • • • • 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 • • • • 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 • • • • • • RECOMMENDATIONS Demonstrate bacteriological evidence by sputum microscopy . 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