DR.

AKHILESH KUNOOR MD,FAPSR

MBBS: T. D. Medical College, Alappuzha(1999-2004)
M.D : SCB Medical College ,Cuttack(2008-2011)
Professor, Amrita institute of Medical sciences, Kochi, Kerala
NTEP State Task Force Vice Chairman ( Kerala)
Member ,Technical Working Group, Latent TB and State level difficult to Treat clinic, Kerala
Coordinator, Amrita Pulmonary Rehabilitation Programme
Governing Council Member APCCM
Immediate past secretary ,Cochin Thoracic Society& Joint Sec IMA Madhyakerala
Member WHO PPM working Group
Publications : (No.) 36
Area Of Interest : COPD, Pulmonary Rehabilitation, Tuberculosis, Public Health
Memberships /Fellowships : ICS,NCCP,ERS,APCCM,IAA,IMA,APSR,ACCP
Awards :
Young Pulmonologist Appreciation Award (APCCM)-2018
Young Pulmonologist Award (APCCM) -2019
nd
 Approach to Pulmonary& Extra
Pulmonary TB
And
Standards in TB Care
Dr Akhilesh K
Professor,Respiratory Medicine,AIMS Kochi
State Task force Vice chairman
Member ,TWG ,LTBI & Difficult to treat TB committee, Kerala
Overvie
w

DIAGNOSIS
TREATMENT
MONITORING
Year Mile stone
1947 TB Division under the Directorate General of Health
Services

1951 BCG Campaign

1956 TRC :Domiciliary treatment
1959 NTI
1962 National TB Program (NTP)
1961-86 Conventional chemotherapy
1986-93 Short Course Chemotherapy
1993 DOTS: Intermittent regimen
1997 RNTCP Rolled out
2011 DOTS Plus
2012 TB Notification
2014 STCI
2016 Revised TOG,Index TB Guideline
2017 PMDT Guideline
2019 NTEP
2021 PMTPT
 NAAT
UNIVERSAL DST

SMCSI MC 22 - 03 - 2016 5
Any persons with any of the symptoms and signs
suggestive of TB including Cough>2 weeks,fever >2
weeks,Significant wtloss,hemoptysis and any
abnormality in Chest xray

• NTEP provides free and quality diagnostic facility at

DMC
• One Designated Microscopy Centre (DMC)
for every 1,00,000 population
(50,000 in tribal/desert/remote/hilly regions)

Test Duration
Gene Xpert 2 Hours
Microscopy 1 day
Line Probe assay 72 Hours
Liquid culture 17 days
Solid culture >30 days
NTP RNTCP NTEP

Chest Xray Sputum microscopy CBNAAT+ Screening CXR

( Universal DST)
Centralised Drug supply Decentralised Drug supply De centralised Drug supply

Daily regimen Intermittent Daily

Long duration Short course chemotherapy Short course Chemotherapy

Unsupervised Supervised Supervised

Interrupted drug supply Uninterrupted drug supply Uninterrupted drug supply

ONLY 30% CURE RATE AND 85% Success rate Extended to Pvt sector
30% Case detection 70% case detection rate Patient centred
[ 12-15% relapse ],INH
Resistance [20%-40%]
Know CXR-A Screening Tool in PTB

Active lesions Indeterminate Inactive lesions

Cavitation Fibrosis Calcifications
Consolidation or soft exudates Ossifications
Infiltrates
 Active Tuberculosis

• Primary • Post primary

• Mediastinal • Cavitation
Lymphadenopathy • Pleural effusion
• Primary lesion – ghon’s • Miliary TB
focus
• Lymphadenopathy with
• Pleural effusion parenchymal shadows
• Miliary TB • Extensive parenchymal
shadows
 Active lesions

Miliary TB Infiltrates
cavity
Consolidation
 Hydropneumothorax
Hilar adenopathy
Collapse
Classical patterns
1) Upper Lobe lesions
2) Craniocaudal distribution
3) Bilateral
4) Centripetal
5) Peri cavitary infiltration / Consolidation
Lower Lung Field TB
*Chest Xray lesion below hila and Para hilar region
-Seen in
 Immunocompromised( DM,CKD,CLD,HIV)
 Pregnancy
 Kyphoscoliosis
 Elderly
TB In HIV TB & DM
CD<200/mm3 Middle & LL
Extrapulmonary Extensive cavitation
Miliary
LNE
Less cavitation
 Xpert Ultra
Xpert MTB/Rif
TB Diagnosis
• Cartridge bases nucleic acid
amplification test Xpert Ultra’s sensitivity is 3% higher than
• Fully automated Xpert MTB/RIF’s (88% vs. 85%), but its
specificity is 2% lower (96% vs. 98%)
• Turn around time-2 hours
• Detect MTB DNA and Rifampicin
resistance (rpoB gene) Rifampicin resistance
• Fast as there is no need of waiting for • Sensitivity and specificity between
culture growth Xpert MTB/RIF and Xpert Ultra are
• Not useful for follow up similar
• Need uninterrupted electricity and
temperature setting(Ambient temp
<30 DegC)
 Xpert MTB/Rif Xpert Ultra

Chamber volume for DNA amplifcation Small chamber Larger chamber

(25 µL) (50µL)

Minimum no.of bacilli for detection 131 bacilli/ml 16 bacilli/ml

Turn aroud time(TAT) 112 mt 65-87 mt

Amplification for TB detection Single target Multitarget:rPo B Core region

rPoB core region Insertion sequence
IS6110 IS6110,1S1081

Resistance detection Real time PCR Melting curve analysis

5 Probes bind to rPo B gene 4 probes bind to rpOB Gene
Site Sensitivity Article
Pleural TB 64.9%(n=317) Wang G etal. Accuracy of Xpert MTB/RIF Ultra for
Spec(8.67%) the Diagnosis of Pleural TB in a Multicenter Cohort
Study.Chest 2019;157(2):268-275

TBM In HIV 69.6%(n=129) Bahr NC etal.

& 95.5%(Vs CRS) Diagnostic accuracy of Xpert MTB/RIF Ultra for
tuberculous meningitis in HIV-infected adults: a
prospective cohort study
. Lancet Infect Dis
2018; 18:68–75
47-60% in HIV negative Predominant population .
Donovan J etal. Xpert MTB/RIF Ultra versus Xpert
MTB/RIF for the diagnosis of tuberculous
meningitis: a prospective, randomised, diagnostic
accuracy study Lancet Infect Dis
2020

Pleural 60.75% D. Perez-Risco, D. Rodriguez-

Temporal, I. Valledor-
CSF 100%
Sanchez, F. AlcaideEvaluation of the
Joint fluid 87.5% Xpert MTB/RIF Ultra assay for direct
detection of Mycobacterium
Ascitis 33.3% tuberculosis complex in smear-
negative extrapulmonary samples
Pericardial fluid 66.6% J Clin Microbiol, 56 (2018)
Interpreting “trace call”

 How frequent?
-Usual categorisation[ High,medium,low,very low,trace]
-Assuming prevalence of 10% of TB in general population1% trace call in HIV negative and
2% in HIV positive
What it indicates?
-Trace corresponds to lowest bacillary burden
-Only the multi-copy targets were detected, and not the TB specific regions in the rpoB
gene.
How to interpret?
-HIV,EPTB,Children- Consider as true positive
-HIV Negative- Repeat sample and if positive consider as true; If negative wait for Culture
-Rif Resistance in Trace sample –Not interpretable ;DST to be done & in PTP SL DST .
XpertUltraFAQs.pdf (who.int)
Truenat(Molbio)

• Chip based micro real time PCR based

test
• Detect TB and Rif resistance separately
• TAT 1 hour
• Truenat MTB-Rif Dx is used sequentially
for RIF resistance detection
• No need of AC or UPS
• Multiple micropippeting steps
• Need of a trained technician
• One test at a time
• Feasible in small volume community
setting
• 0.5 ml sample Vs I ml of Xpert MTB
 Line probe assay • Results of LPA are interpreted based on
development/ absence of Wild Type (WT)
Molecular Test detecting DST for First line and Second and Mutant (MUT) bands.
line drugs –INH, Rifampicin,FQ etc
• Resistance not detected: all Wild(WT)
probe developed. No mutant(MUT)
developed

• Resistance inferred: One or more WT

developed ;No of the MUT probes in the
corresponding region are developed.

• Resistance detected: One or more MUT

developed ; WT probes may or may not
developed
Integrated Diagnostic Algorithm
TREATMENT
DAILY REGIMEN with 28 days package
Weight band based
SMCSI MC 22 - 03 - 2016 22
 9HRE
2HRSE+7HR
6-9RZ+E
2HSE+10
HE

18-24SLE
 Drug Stage 1-3 Stage4&5 Renal
TB with CKD Transplant
recipient
INH 300 mg OD 300 mg OD or 300 mg OD
15 mg/kg
max900 mg
thrice weekly

Rifampicin <50 kg 450mg <50kg 450 mg <50kg 450 mg

OD OD OD
≥50 kg 600 ≥50 kg 600 ≥50 kg 600
mg OD mg OD mg OD

Dialysis patients Pyrazinamide <50 kg- 1.5 g

daily
25-30 50 kg- 1.5 g
mg/kgx3/wee daily
>50 kg:2g k >50 kg:2g
 Immediately after daily daily

dialysis-Raised drug level Ethambutol 15 mg/kg 15-20 mg/kg 15 mg

 4-6 hours before dialysis daily thrice a week /kgdaily

– premature drug
removal; toxicity less
BTS Guideline 2010 and TOG 2016
 Drug Resistant TB
Regimens

All oral H Longer Oral MDR (18-20) Bdq(6) Lfx Lzd#

mono-poly (6) Lfx R E Z Regimen Cfz Cs
DRTB (Max 9 months)
regimen@

Short Oral BdQ Containing Regimen ( 4-6)Bdq(6m),Lfx,CfZ,Z,E,Hh,Eto

+
(5) Lfx,CfZ,Z,E
Extra Pulmonary
Tuberculosis
• HIV Negative • HIV Positive
Case Definitions
1)Presumptive case:
A patient with symptoms and signs of EPTB who need to be investigated

2)Bacteriologically confirmed case:

A patient who has a microbiological diagnosis of EPTB, based on positive
microscopy, culture or a validated PCR-based test.

3)Clinically diagnosed case: A patient with negative microbiological tests

for TB (microscopy, culture and validated PCR-based tests), but with
strong clinical suspicion and other evidence of EPTB, such as
compatible imaging findings, histological findings, ancillary diagnostic
tests or response to antiTB treatment.
 A Good Medical
Knowledge and History
Taking –ESSENTIAL!

PCR Paucibacillary
Based
Tests  Atypical and variable Presentation
Lengthy Period from Initial symptoms
Histop
to detection
Cultur
e EPTB atholo
gy
Invasive Techniques needed
Low Sensitivity for Diagnostic Tests
and CBNAAT
Imaging TB Mimickers
Diagnosis of EPTB

• Constitutional and organ specific symptoms

• Contact history with TB
• Organ specific imaging
• Nucleic Acid Amplification test & Culture
• TST/IGRA/C-TB- Adjunct
Case scenario

• 29 year old female from Calicut

• H/o Loss of appetite-3 months
• Lower abdominal pain-2months
• Low grade fever -2 months
• Weight loss, abdominal distension-2 months
• Evaluated outside
- Peripheral smear, OGDscopy and Colonoscopy- Inconclusive
Ascites Fluid Analysis
-Lymphocytic
Infection
-SAAG -4 Malignant
-ADA-4 LDH-52 Sarcoidosis
Peritoneal Biopsy-Granulomatous peritonitis GPA
Lymphoproliferative Disease
CEA-2.02 ng/ml CA 125 74.74 U/ml CA 19-9 66.1 FB Contamination
LDH-179 U/L
 Treated as clinically diagnosed but withheld due to DILI
USG abdomen –Altered echo texture, a large fluid collection
Ultra – High Sensitivity in
H/P Second opinion EPTB,PLHIV and Children
Peritoneal Biopsy-Granuloma No Caseation
MDCT Abdomen-Thick walled abdominal Collection
Genexpert(ULTRA)-MTB
Detected Trace
Test Patient Comments
Work
CXR/HIV Up All Rule out PTB
Integrated counselling
Ascitic fluid All Cytology,ADA,Albumin and
protein,AFB Smear,AFB
culture,Routine C& S
USG abdomen All Ascites,Omental thickening,
Mesentric adenopathy
USG Guided FNAC/Core biopsy Selected
SAAG<1.1
Microscopy &Culture of
from Mesentric or FNAC/Biopsy specimen than fluid
RPLN ,omentum,peritoneum High protein (>2.5 g/DL) alone
ADA >39 IU/L Send for H/P,M/C copy, Culture

CT/MRI Abdomen Selected Diagnostic Uncertainty

 Sensitivity in Smear AFB
Laproscopy Selected(
and Cost,Low
AFB Culture Invasive)  Tubercles in thickened
 PCR – Variable accuracy peritoneum,omentum and Liver
( No Recommendation)  Fibro-adhesive peritonitis
Targeted Diagnostic sample
increase yield
• Kaberr K shah eta.Histopatholgy rview of granulomatous inflammation.Journal of clinical
tuberculosis and other mycobacterial diseases.Volume 7, May 2017, Pages 1-1
General recommendations

• Total 6 months of Treatment ( 2 HRZE+4 HRE)

• TB Meningitis-9 Months
• Bone& Skeletal TB-12 months (2+10)
• Treatment extension as per clinical response
• Inadequate resolution ,repeat Culture and DST
• Attempt for microbiological diagnosis with at least CBNAAT and culture if possible
• CBNAAT have good sensitivity in LN TB and TB Meningitis
• Steroids-Cardiac TB, TB Meningitis, Ocular TB,Paradoxical reactions
Universal DST in Extrapulmonary TB

• Universal DST Policy Could detect 52.8% DR TB Cases in India.

Samples and Volume Required
Take sample in Normal saline
Pus 0.5 ml
Tissue 1 cm
Fluid 0.5 ml
 Tuberculoma

Epidural abcess Ileocaecal mass

Serpigineous
Choroiditis Basal Exudates
Adenosine Deaminase ( ADA)
• Adjunct test for diagnosis in EPTB

Pleural fluid -70 ( definite) 40 Exudative

( Probable) Lymphocytic
Ascitic fluid -39 SAAG<1.1 in ascites
CSF -10 Cob Web Coagulam
High Protein Low sugar fluid in
CSF
Monitoring

Strategies Clinical monitoring

• NOTIFICATION • Baseline LFT, Ophthalmic check up
• DOT • Monthly(Symptoms, weight gain)
• TREATMENT SUPPORT PROGRAM ( In Kerala Fortnightly)
- Accessible ,accountable ;Even
• AFB Smear –End of IP and CP
family member
• Comorbidity management
- Health facility will supervise TS
-Incentives • ADR
-ICT Modalities(SMS,99 DOTS)
 All Diagnosed
All patients starting treatment
Both Bacteriologically positive &
Clinically diagnosed

IPC 269& 270-Failure to notify

Community Medicine 14-10-2015

 Adverse Drug Reactions

Drug ADR
Isoniazid Peripheral
neuropathy,Hepatitis,Seizure,Psychosis,
Alopecia
Anemia

Rifampicin Hepatitis,Flu like syndrome,Abdominal

syndrome,Respiratory syndrome
Thrombocytopenia

Ethambutol Retrobulbar neuritis

Hyperuricemia
Pyrazinamide Hyperuricemia
Fulminant hepatic failure
 ADR Management

Dermatological Reactions

• Mild- Itching of skin with or without rash( Usual-R,Z)

• Moderate to Severe:Clinical Presentation hives (raised, itchy rash) with or without fever
INH < rifampin < PZA < ethionamide < cycloserine < ethambutol < para-aminosalicylic acid <
streptomycin

Management

1. Discontinue all drugs

2. Rule out a viral infection a. full physical exam
3. complete blood count
. Discontinue all drugs until the reaction resolves

. Identify the causative drug by rechallenging (restarting) each drug every 4 days .
Drug Induced Liver Injury( DILI)

• In the absence of symptoms, elevation of transaminases up to 5 times the upper

limit of normal (ULN) and in the presence of symptoms up to 3 times the ULN or
twice the ULN of bilirubin constitutes DILI provided competing causes such as
acute viral hepatitis, autoimmune hepatitis and others liver diseases are ruled
out.

SEVERITY
Grade 1: transaminases 1.25 - 2.5 × upper limit of normal
(ULN)
Grade 2: 2.6 - 5 × ULN
Grade 3: 5.1 - 10 × ULN;
Grade 4: >10 × ULN
 Hepatic adaptation

• 20% of patients may develop elevated liver enzymes

• Asymptomatic
• Self Limiting

Hepatotoxic Potential Risk Factors for DILI

Z>H>R  Old age
Fulminant Hepatic failure-Z  Malnutrition
 Alcoholism
R+H=Hepatoprotective potential
 Viral Hepatitis B and C
R+Z>H in hepatotoxicity  Genetic polymorphism(N-acetyltransferase
2 (NAT2), CYP 2E1 and glutathione S-
transferas)
 Dosing schedule (daily>intermittent)
Management of DILI

• Withhold ATT
• If Enzymes <2 times ULN rechallenge

BTS
E>INH>Rif>Z
ATS
E>R>H>Z
Start with lowest Possible dose and hike up every 3 days with LFT Monitoring
Hepatoprotectives may be added-Acetyl cysteine,Ursodeoxycholic acid
PEDIATRIC TB
Pediatric TB Drug Dose
TB Prevention
Treatment
Rationale for TPT

• 71% Household contact have baseline TBI

• 2% develop active disease
• Increased risk in Bacteriologically positive(25 times),HIV(16-25
times) ,immunocompromised(3-4 times)
• The risk of developing TB disease after TPT decreases by 60% and upto 90% in
PLHIV
TPT hasten the rate of Decline of iTD
from 2.5% to 10% Required annually
NSP 2017-2025)- End TB 2025
PREVENT
Build
Detect Treat
 TPT Regimen –Kerala policy
Category Regimen Test ( IGRA)
PLHIV CLHIV 6H Not required
HHC <5 years 3 HR Not required
HHC 5-15 years 3 HR Required
HHC>15 years 3 Required
HP( Weekly)
Other Risk Groups 3 HP/6H Required
- Organ Transplants
- Dialysis
- Silicosis
- Immunosuppressants( TNF
Alpha Inhibitors)
Contacts of R resistant 6 Lfx Required
DR TB ( Rolling out among 12
Patients H Resistant 4R states)
Private Sector Engagement In TB
Sector
Summary of Joint Effort for
Elimination of TB
• Single window system in private hospital
STEPS • Ensuring all Public Health Actions to all

Private Hospital • Consortium of Hospital Managements

Consortium • Establishing STEPS, policy support & Review

Coalition of Professional • To sensitise and support specialists

Medical Association • To advocate with doctors for following STCI
 NTEP to STEPS centers

• Free Diagnostic Services

CB NAAT,Liquid Culture & DST (Selected samples),Collection of specimens from private
hospitals
• Free Treatment
Daily Fixed Dose Combinations and loose drugs for modifications
DST guided regimens, INH Mono/poly, DR TB Regimens
• Adherence Support & Public Health actions
Retrieval, Contact Investigation(if requested)
AIC Kit
DBT, TB Pension
Support for TB Notification
Training and Capacity building
Expectations from Private
Partners
• Ensure all patients receive Standards of TB Care in India.

• Notify all TB cases.

• Report Outcome of all notified patients.

• Ensure all Public Health Actions to all the TB patient.

STEPS Inauguration
THANK YOU