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Recent Advances in Diagnosis & Treatment of Childhood

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RECENT ADVANCES IN DIAGNOSIS & TREATMENT TREA TMENT OF OF CHILDHOOD CHILDHOOD TB DR.K.S.KUMARAVEL





TB AND HIV ARE THE DISEASES LARGELY IN THE PUBLIC DOMAIN. CLOSE CO-0PERATION BETWEEN CLINICIANS AND PUBLIC HEALTH ARE PIVOTALS TO THE SUCCESSFUL ERADICATION OF TB.





TB AND HIV ARE THE DISEASES LARGELY IN THE PUBLIC DOMAIN. CLOSE CO-0PERATION BETWEEN CLINICIANS AND PUBLIC HEALTH ARE PIVOTALS TO THE SUCCESSFUL ERADICATION OF TB.

STOP TB PARTNERSHIP * DEVELOPED BY WHO & IUA IUATLD. TLD. * RELIES UPON ‘DOTS’ STRATEGY AND RNTCP.

* MOST OF THE CURRENT GUIDELINES ARE BASED ON THIS. * IAP ALSO ENDORSES THIS.

www.stoptb.org

DIAGNOSIS OF TB •

CAREFUL H/O



CLINICAL EXAMINATION



TUBERCULIN TESTING



BACTERIOLOGICAL CONFIRMATION



INVESTIGATIONS RELEVANT TO TYPE OF TB



HIV TESTING

USEFULNESS OF SCORE CHARTS •

Eg: CROFTON, HOME & MILER.



NOT VALIDATED



NOT EVALUATED ADEQUATELY





THEY CAN BE USED AS A TOOL FOR SCREENING AND NOT FOR DIAGNOSIS PERFORM POORLY IN HIV INFECTED CHILDREN

TUBERCULIN SKIN TESTING (TST) •



TB INFECTION DOES NOT NECESSARILY MEAN DISEASE VERY USEFUL IN DIAGNOSING LATENT INFECTION

NEW GUIDELINES FOR INTERPRETATION OF TST •

TST IS CONSIDERED POSITIVE WHEN > 5 mm IN HIGH RISK CHILDREN ( HIV INFECTED AND MALNOURISHED ) > 10 mm IN ALL OTHER CHILDREN IRRESPECTIVE OF THEIR BCG STATUS.

FALSE POSITIVE TST •



INCORRECT INTERPRETATION OF TST.

NON TUBERCULOUS MYCOBACTERIA INFECTION.

FALSE NEGATIVE TST •

INCORRECT TECHNIQUE



HIV



VIRAL INFECTIONS – MEASLES



VACCINATION



IMMUNOSUPPRESSION



SEVERE TB



LOW PROTEIN STATES

SPUTUM AFB

SPUTUM AFB •





GOLD STANDARD FOR DIAGNOSING TB.

NOW TWO SAMPLES ARE ADVICED  – SPOT AND NEXT DAY. RECONFIRMATION IS NOT NECCESSARY

CULTURES

CULTURE ON SOLID MEDIA •





AGE OLD TECHNIQUE USING LJ MEDIUM.

DRUG SENSITIVITY TESTING CAN ALSO BE DONE. DISADVANTAGE IS TAKES A LONG TIME.

CULTURES ON LIQUID MEDIA •









NEWER TEST CALLED “BACTEC” / “BACT ALERT” RADIO METRICALLY DETECTS FLOURESCENCE IN MEDIA TO INDICATE PRESENCE OF BACTERIAL GROWTH. DST CAN ALSO BE DONE. RELATIVELY FASTER RESULTS THAN SOLID CULTURE MEDIA ( 7-14 DAYS FOR DIAGNOSIS AND ANOTHER 7-14 DAYS FOR DST) AVAILABLE IN INDIA.

MOLECULAR LINE PROBE ASSAY •

AVAILABLE AS “GENOTYPE MTBDR” AND LIPA -

RIF. •



DONE IN A AFB POSITIVE SPECIMEN. STRIP TEST DETECTS KNOWN GENETIC MUTATIONS IN A SMEAR POSITIVE.



VERY USEFUL FOR DETECTING MDR-TB.



AVAILABLE IN INDIA.

PCR BASED TESTS •





CURRENTLY UNABLE TO DIAGNOSE TB IN CHILDREN WITH ACCURACY. SPUTUM BASED PCR GIVES VARIABLE RESULTS AND IS OF LIMITED VALUE. WHO DOES NOT ENDORSE PCR BASED TESTS FOR TB.



WIDELY AND EASILY AVAILABLE IN INDIA.



SPECIMENS INCLUDED ARE SPUTUM, CSF, ETC.

SEROLOGICAL TESTS •



• • • •

IgG, IgM AND IgA ANTIBODIES AGAINST TB CAN BE MEASURED IN SERUM. IgA ANTIBODIES CAN BE SEEN RAISED IN SEROSAL AND MENINGEAL TB. NOT FULLY STANDARDISED NOT SENSITIVE AND NOT SPECIFIC. OFTEN LEADS TO MISDIAGNOSIS. WHO HAS ASKED ALL THE COUNTRIES TO BAN THESE SEROLOGICAL TESTS IN ITS LETTER DATED 20/07/2011.

NUECLIC ACID AMPLIFICATION TESTS •













ENDORSED BY WHO DNA AMPLIFICATION BY PCR AND REAL TIME ANALYSIS AVAILABLE IN INDIA (SRL) AS XPERT MTB - RIF, GENE PROBE TB AND AMPLICOR FULLY AUTOMATED GIVES RESULTS WITHIN 2 HOURS ANALYSES SPUTUM SPECIMEN FOR AFB AND DOES SENSITIVITY FOR RIFAMPICIN. IF AVAILABLE WIDELY, WILL REVOLUTIONALIZE DIAGNOSIS OF TB, ATLEAST IN ADULTS.

INTERFERON GAMMA RELEASE ASSAY •

AVAIALBLE AS “QUANTIFERON GOLD IN TUBE TEST” AND “TB SPOT TEST”



AVAILABLE IN INDIA WIDELY.



DETECTS LATENT TB INFECTION



MEASURES IN VITRO PRODUCTION OF GAMMA INTERFERON BY SENSITISED

T-LYMPHOCYTES.

INTERFERON GAMMA RELEASE ASSAY •



DOES NOT DIFFERNTIATE LATENT TB FROM DISEASE. REGARDED AS “ COSTLY MANTOUX” BY

SOME. •



APPROXIMATELY COSTS RS.3000. (MICROBIOLOGICAL LAB)

RESULTS ARE SHOWN AS POSITIVE, NEGATIVE OR INDETERMINATE.

INTERFERON GAMMA RELEASE ASSAY •

VERY HIGH SPECIFICITY



NOT AFFECTED BY BCG VACCINATION



NOT AFFECTED BY OTHER MYCOBACTERIA



RESULTS AVAILABLE IN 24 HOURS.

TREATMENT OF CHILDHOOD TB

CONVENTIONAL TREATMENT •

IAP ENDORSES ‘DOTS’ STRATGY FOR

CHILDHOOD TB. •



CHOICE BETWEEN DAILY THERAPY AND DOTS RESTS WITH THE CLINICIAN. DOTS STRATEGY ENSURES GOOD COMPLIANCE AND ADHERENCE TO THERAPY.

DOTS Vs DAILY THERAPY •

ALMOST ALL AVAILABLE STUDIES CONCLUDE THAT ‘DOTS’ IS AS EFFECTIVE AS DAILY

THERAPY.

DOSAGE OF FIRST LINE ATT DRUGS DRUG

DAILY DOSE (mg/kg/day)

THRICE WEEKLY DOSE (mg/kg/dose)

INH

5

10

RIFAMPICIN

10

10

PYRIZINAMIDE

25

35

STREPTOMYCIN

15

15

ETHAMBUTOL

20

30

DOTS •

DIRECTLY

OBSERVED TREATMENT

- SHORT COURSE

DOTS – WHAT’S NEW? •

ONLY 2 TREATMENT CATEGORIES

NEW & PREVIOUSLY TREATED •

CATEGORY III PHASED OUT



NEW CATEGORY IV IS INTRODUCED

NEW CASES (INCLUDES FORMER CAT I & II) •

New smear-positive pulmonary TB



New smear-negative pulmonary TB



New extra pulmonary TB



Severe concomitant HIV disease 2HRZE / 4HR or 6HE



FOR TB meningitis 2RHZS / 7RH

PREVIOUSLY TREATED (OLD CATEGORY II) •

Previously treated smear-positive

pulmonary TB: #relapse

#treatment after interruption #treatment failure

2HRZES / 1HRZE / 5HRE

CATEGORY III

PHASED OUT

RECENT ADVANCES IN TREATMENT OF TB

INTRODUCTION OF CATEGORY IV •



FOR CHRONIC/MDR TB

REGIMEN STANDARDISED FOR INDIVIDUAL PATIENT

STANDARD CATEGORY IV •





Z-Km-Lfx-Eto-Cs-PAS IN THE INTENSIVE PHASE FOR 6 MONTHS OR UNTIL SPUTUM SMEARS AND CULTURES ARE CONTINOUSLY NEGATIVE. CONTINUATION PHASE WITH FEWER DRUGS FOR 12-18 MONTHS. DAILY THERAPY IS GIVEN.

DOTS PLUS CLINIC •





THESE CLINICS CATER TO THE NEEDS OF PATIENTS WITH MDR-TB AND GIVE CAT-IV TREATMENT. COST OF CAT-IV TREATMENT PER DAY IS RS.400. OUR NEAREST CLINIC IS COIMBATORE MEDICAL COLLEGE HOSPITAL.

EMERGENCE OF XDR-TB •



THIS IS EXTREMELY DRUG RESISTENT FORM OF TB. BY DEFINITION IT IS TB WHICH IS RESISTENT TO INH, RIFAMPICIN, ATLEAST ONE QUINOLONE AND ATLEAST ONE INJECTABLE SECONDLINE DRUG.

TDR-TB •







TOTALLY DRUG RESISTENT TB

STRAINS OF TB THAT ARE RESISTENT TO MORE NUMBER OF DRUGS THAN XDR-TB. THERE ARE 4 PUBLISHED REPORTS OF TDR-TB WORLD WIDE. GOVT OF INDIA REFUTES CLAIM THAT TDR-TB EXISTS IN INDIA.

USE OF ETAHMBUTOL •

IN THE PAST, IT WAS OMITTED IN CHILDREN DUE TO CONCERNS REGARDING MONITORING FOR OPTIC NEURITIS.



NOW IT IS FOUND TO BE SAFE IN CHILDREN.



DOSE: 20MG/KG

CONTACT SCREENING •

ASYMPTOMATIC UNDER 5 CHILDREN SHOULD BE TREATED WITH 6H.

BCG VACCINATION •



EFFICACY OF BCG TO PREVENT ADULT FORMS OF TB VARIES FROM 0-80% IN VARIOUS STUDIES. IT OFFERS PRTECTION AGAINST MORE SEVERE FORMS OF TB IN YOUNG CHILDREN

BCG VACCINATION •



NEONATES OF SERO POSITIVE MOTHERS SHOULD ALSO RECEIVE BCG VACCINE. CHILDREN WHO HAVE AIDS AND MISSED THEIR NEONATAL BCG SHOULD NOT BE GIVEN BCG NOW.

EMPIRICAL ATT •

THERE IS NO ROLE FOR STARTING A PATIENT ON TRIAL OF ATT FOR A FEW DAYS, AS THIS WILL LEAD TO EMERGENCE OF MDR-TB.

EMPIRICAL ATT •

STANDARD CASE DEFINITION IN RNTCP GIVES THE CLINICIAN LIBERTY TO TREAT A CHILD HAVING PNEUMONIA WITH ATT, EVEN IF SMEAR FOR AFB IS NEGATIVE IN THE FOLLOWING SITUATIONS…

# RADIOLOGICAL ABNORMALITIES CONSISTENT WITH TB # NO RESPONSE TO A COURSE OF BROAD SPECTRUM ANTIBIOTICS # DECISION OF A CLINICIAN TO TREAT A CHILD WITH FULL COURSE OF ATT.

HOW IAP GUIDELINES DIFFER? •

IAP ENDORSES DOTS STRATEGY OF RNTCP.

IAP GUIDELINES •

PREVENTIVE THERAPY Asymptomatic Mantoux positive <3 years Asymptomatic Mantoux positive <5 years with Grades 3 or 4 malnutrition. Mantoux +ve - Recent converter/no signs. Children <3 years with H/O +ve contact. Children <5 years - Grades 3 or 4 malnutrition with H/O +ve contact.



Treat with

6HR

IAP GUIDELINES •

NEUROTUBERCULOSIS

2HRZE/10HE

TB & HIV

WHO RECOMMENDS ROUTEINE HIV SCREENING FOR ALL PATIENTS WITH TB IN HIGH HIV PREVALENCE AREAS

CURRENT GUIDELINES •



TB IN HIV INFECTED CHILDREN SHOULD BE TREATED AS IN UNINFECTED CHILDREN. WHEREVER POSSIBLE RIFAMPICIN SHOULD BE INCLUDED FOR THE ENTIRE PERIOD OF TREATMENT.

ATT OR ART – WHICH IS TO BE STARTED FIRST?

ALWAYS START ATT FIRST…

ART SHOULD BE STARTED AFTER 2-8 WEEKS OF ATT.. TREATING TB IS A PRIORITY. CHRONIC TREATMENT FOR HIV CAN BE STARTED AFTER 2-8 WEEKS.

IRIS •

IMMUNE RECONSTITUTION INFLAMMATORY  SYNDROME 





DEVELOPS IN A CHILD ON ATT, WHEN STARTED ON ART. DUE TO IMMUNE SYSTEM RECOVERING AND MOUNTING A RESPONSE.

IRIS •



WORSENING OF SIGNS OF TB.

SHOULD NOT BE MISTAKEN FOR FAILURE OF TREATMENT.



TREATED WITH STERIODS AND NSAIDS.



USUALLY LASTS FOR 2-10 WEEKS.

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