Dr. Akhilesh Kunoor is a pulmonologist and professor in Kerala who has expertise in tuberculosis, COPD, and pulmonary rehabilitation. His background includes degrees from medical colleges in India and postgraduate training. He currently works at Amrita Institute of Medical Sciences and holds several roles related to tuberculosis prevention and treatment in Kerala.

1. 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, Secretary, Cochin Thoracic Society
Publications : (No.) 32
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
Best oral presentation ( 2nd prize)-Consultant (NAPCON 2019)

2. National Guideline for Programmatic
management of Tuberculosis
Preventive Treatment
Dr Akhilesh K
Professor, Respiratory Medicine,AIMS Kochi
State Task Force Vice chairman,NTEP,Kerala
Member-Technical Working Group LTBI &
State level Difficult to treat TB Clinic, Kerala
Attended national TOT in PMTPT

3. Case scenario
• 46 year old lady presented with 2 weeks of cough with scanty expectoration
,Weight loss for the last 6 months. She is diagnosed as pulmonary TB by sputum
NAAT. She resides with 4 year old daughter 14 year old son 70 year old mother
and 26 year old sister in law who is pregnant along with her husband( 50 year
old) who is a chronic alcoholic A
 What should be the policy for TB prevention treatment in this family?

4. Overview
• Nearly 35-40 crores Indian population having TBI
• 5-10% of TBI will develop disease over their life within 2 years of initial infection.
• The risk is increased in certain conditions
 > 25 times - Contacts of Bacteriologically positive
16-25 times -HIV
3-4 time -Other immunocompromised (eg DM)

5. Magnitude of the problem&
Rationale
• 35-40 crores- TBI in Indian population
• 5-10% of TBI will develop disease over
their life within 2 years of initial
infection
• Increased risk in Bacteriologically
positive(25 times),HIV(16-25 times)
,immunocompromised(3-4 times)

6. • 71% House hold contacts of pulmonary TB patients have baseline TBI and
2% develop active TB
• If untreated there is a chance of active TB in children
< 1year -40%
1-10 years -24%
11-15 years -16%
• The risk of developing TB disease after TPT decreases by 60% and upto
90% in PLHIV

7. • National strategic plan( NSP 2017-2025)- End TB 2025
• Scaling up TPT would be key to hasten the rate of decline in TB incidence from
2.5% at present to 10% required annually.
Detect Treat Prevent Build
PREVENT

8. TB Infection vs Active TB
TB Infection Active TB
No Symptoms Symptoms present
Investigations for disease are negative
CXR
Sputum microscopy/NAAT
HPE/Radiology
Investigations for disease are positive
CXR
Sputum microscopy/NAAT
HPE/Radiology
Investigations for infection are positive
IGRA
TST ( Mantoux)/ C-TB
Investigation for infection should not be done

9. Definitions
• Adult: Person over 19 years of age.
• Child: up to and including 18 years of age. [This include adolescents aged 10-18 years.]
• Contact investigation: is a systematic process for identifying previously undiagnosed people with TB disease
and TB infection among the contacts of an index TB patient
[ identification, clinical evaluation and/or testing and provision of appropriate anti-TB treatment (for people
with confirmed TB) or TB preventive treatment (for those without TB disease)].
• Close contact: is a person who is not in the household but shared an enclosed space, such as at a social
gathering, workplace or facility, for extended periods during the day with the index TB patient during the
three months before commencement of the current TB treatment episode.
• High TB transmission setting: is a setting with a high frequency of individuals with undetected or
undiagnosed TB disease, or where infectious TB patients are present and there is a high risk of TB
transmission. [untreated/ inadequately treated, aerosol-generating procedure, presence of susceptible
individuals]
• Household contact (HHC): is a person who shared the same enclosed living space as the index TB patient for
one or more nights or for frequent or extended daytime periods during the three months before the start of
current TB treatment. ( Close contacts are inclusive)

10. Diagnosis of TB Infection
• No gold standard test for diagnosing TBI or predicting progression of TBI to TB
Disease
Tuberculin skin test Immune sensitisation to
Interferon Gamma Assay(IGRA) Mycobacterial Antigen
( Type 1V or delayed Type 2)
Kerala adopted IGRA for use of LTBI( Can do in a single sitting, no cross reaction
with BCG)
Identified Public and private facilities and logistics
Need transport within 8-30 hrs of sample collection
Update test request and results in the Prevent TB India app (later on TBI module of
Nikshay whenever available) to enable documentation and reporting of TST results.

11. Target population & Policy
Target Population Strategy
PL HIV
-Adults and children>12 months
-Infants <12 months with HIV in contact with active TB
HHC<5 years of active PTB patients
Rule out TB( Chest Xray and symptoms)
TPT
HHC>5 years of active PTB Rule out active TB
Test for TBI(IGRA)
TPT if TBI positive only
High risk Groups
Immunosuppressants
Anti TNF alfa
Dialysis
Silicosis
Preparing Organ /Hematological transplant
Rule out active TB
Test for TBI(IGRA)
TPT if TBI positive only
NO TEST or TPT
DM
Smokers
Alcoholic
High risk transmission setting-Map for future
strategies
TEST&
TREAT
TPT Must not be deferred in the absence of IGRA
/Chest Xray

12. Enumerating target population & Contact
Tracing
• Weekly list of PLHIV ,HHC and other risk group -All health facility
• PLHIV enrolled for ART-ICTC & ART Centres( Update on Prevent TB
App)
• Index Pulmonary ( Microbiolgically positive) TB patients- ACF,Passive
or Intensified case finding –Nikshay
• Contact tracing by initial home visit or telemedicine by HCWs
• Institution providing care to risk groups to be mapped out and engage

13. Ruling out of active Disease
TPT should be given
after ruling out active
TB irrespective of
level of
immunosuppression,
pregnancy ,Previous
ATT

14. Cascade of Care Approach

15. Losses and
Drops outs in
cascade of
care

16. Contraindications of TPT
• Active TB disease
• Acute or chronic hepatitis
• Concurrent use of other hepatotoxic medications (such as nevirapine)
• Regular and heavy alcohol consumption
• Signs and symptoms of peripheral neuropathy like persistent tingling, numbness and burning
sensation in the limbs
• Allergy or known hypersensitivity to any drugs being considered for TPT
• Pregnancy or previous h/o TB are not contraindication

17. Counselling
Rationale for TPT , protective benefits to the individual, the household , community
Free availability of TPT under NTEP
TPT regimen, duration, drug intake , follow-up schedule
Potential side effects, adverse events and its management, importance of compliance
Reasons and schedule of regular clinical and laboratory follow-up for treatment monitoring;
Signs and symptoms of active TB and need of health care visit.

18. • Treatment supporter:
 Assess if a treatment supporter is needed or self-administration is possible
 Trained family member/ community volunteer/ workplace treatment partner or
health-care workers.
DOTS by Treatment supporter if for weekly regimen

19. Pre-treatment evaluation
History
Personal History:
• Allergy/hypersensitivity (INH, Rif,
Rifapentin, Rifabutin)
• HIV Status ,ART Regimen
• Pregnancy status, Birth control method
• Comorbidities
( malnutrition,diabetes,CLD)
Drug History:
ARV,Opiods,Antimalarials –interaction with TPT
Social and financial assessment:
Barriers for completion
Clinical
LFT:
-Routine baseline test not recommended
-In risk group ,strongly suggested
(CLD,H/o liver disease, alcohol, HIV, pregnancy,
immediate post partum period)
Weight measurement: In Children

20. Responsibility of a medical officer
• TPT Initiation
• Monitoring
• management of adverse event
• declaring treatment outcome
• long term follow up

21. TB Preventive Treatment
• Shorter Rifamycin based regimen ( 3 HP)
-Similar preventive efficacy
-High completion rate( 82% Vs 60% with 6H)
- Low Risk of Hepatotoxicity
-Less Adverse Drug reactions

22. TB Preventive
Treatment
Target Population Treatment Option
PLHIV( adults and
children>12 months)
6 H daily
Infants <12 months with
contact with active TB
6 H
HHC Below 5 years of PTB
patients
3 HP
6 H
HHC>5 years of PTB
patients
3 HP
6 H
Other Risk Groups
Immunosuppressive
therapy
Silicosis
AntiTNF Alpha treatment
Dialysis
Transplantation
3 HP
6 H

23. TPT Regimen-Kerala Policy
Category Regimen Test ( IGRA)
PLHIV CLHIV 6 H Not required
HHC <5 years 3 HR Not required
HHC 5-15 years 3 HR Required
HHC>15 years 3 HP( Weekly) Required
Other Risk Groups 3 HP/6H Required

25. 6 H
ISONIAZID
Daily
182 doses
Pill burden/dose
Safe in Pregnancy
Safe with ART
Absorption-Better in empty stomach
50% reduction with meal
3 HP
ISONIAZID+RIFAPENTIN
Weekly once
12 doses
Pill burden/dose
-9 pills/loose drugs& 3 pills / FDC
Pregnancy-Not Indicated
Contraindicated-Drug interaction with
ART
Peak concentration increased with meal

26. Contacts of DR TB Patients

27. Post treatment PLHIV/CL HIV
• All PLHIV/CLHIV In patients who had successfully completed
treatment for TB Disease earlier should receive a full course of TPT
after completing TB Treatment
In patients previously treated for TB, post-treatment TPT has been considered in view of the 5-7 times
higher risk of recurrence of TB among PLHIV and nearly 90% of these due to re-infection (11).

28. Role of Pyridoxin
Infrequent AE- Peripheral neuropathy
Symmetrical numbness and tingling in extremities
Risk groups
• Malnutrition
• Chronic alcohol dependence
• HIV
• Renal failure
• DM
• Pregnant/Breast feeding
Treatment: Withdrawal of INH and High dose pyridoxin(100mg/day)
Prophylaxis:
Children-10 mg/kg/day
Adults -25 mg/day
PLHIV- 50 mg/day

29. • Even if pyridoxin not available TPT to be given
• In High Risk group Multi Vitamin B Complex can be substituted
• Close monitoring for Adverse events
Emergence of Drug Resistance:
• No evidence with TPT
• Ruling out active disease is important before TPT
• Rapid DST if TB detected before,during or after TPT

30. Management of adverse events
Adverse event Stop and reintroduce Stop and do not reintroduce
Flu like syndrome Mild- Continue treatment & Observe Moderate to severe- Change to 6 H
Drug Fever If fever<39 deg Fever> 39 deg after reintroduction
Persistent nausea,vomiting,diarrhea Antiemetic/Antidiarrheal
Cautious reintroduction of 3 HP
Diarrhoea/nausea which needing
rehydration
Cutaneous reaction Diffuse rash with no or limited
vesicles
Extensive bullous lesion,Mucosal
ulceration,SJS,TEN
Hepatitis No symptoms and liver enzymes<5
times normal
Liver enzymes>5 times normal
without symptoms or >3 times with
symptoms
Psychosis,seizure Antispychotics, antiepileptic If persistent
Hypersensitivity reaction If severe use 6 H

31. Special Situations
Pregnancy & Birth Control
• 6 H Safe in Pregnancy
• On Rifamycins – OCP failure-Use barrier contraceptives or IUDs
• In women having hormonal contraceptive implants, the interval for replacing the
implants may need to be shortened from 12 weeks to eight weeks
Liver Disease
TPT with caution in baseline transaminase >3 times ULN
Defer in end stage Liver disease
In acute hepatitis defer until acute illness resolved
6 H tolerated in chronic Hepatitis B and C

32. Special situation

33. • Renal Failure
• Safe to use
• Severe renal failure-Pyridoxin to be given
• PLHIV
-Rifampicin and Rifamycin can be co administed with efavirenz
-Higher dose of Raltegalvir(800 mg BD) to be used
-Should not be co administed with protease inhiBtors or nevirapin

34. • Babies Born to mothers with TB disease
-If baby is un well, paediatric referral
-Ensure treatment for mother
-Ensure infection control
-If baby is well TPT may be provided
-BCG vaccination should not be delayed even if TPT is given
-Pyridoxin 10 mg/kg/day during TPT and while on mothers treatment ( If breast
fed)
-HIV exposed and patient on nevirapine 6 H can be safely given
-Breast feeding can be continued

35. • People who use drugs
- Safe to use 6 H
- Monitor Liver toxicity
Contacts of MDR TB
• MDR with FQ Sensitive-6 Lfx
• If H is susceptible in R resistant -6 H
• H Resistant with R sensitive -4 R

36. Monitoring
• Preferably taken under direct supervision of health worker
• If not, establish strong adherence mechanism
family treatment supporter
audio/video call weekly on the day of intake
• Provide treatment card
• Documentation in TPT register at TU level
• Once monthly clinical follow up

37. Management of
Interruption

38. TPT Regimen Missed period Action plan
6 H,6 Lfx,4R <2 weeks
> 2 weeks
Continue the same +Add number of missed doses
If Interruption after > 80% of Dose intake continue and
complete remaining
If <80% dose taken and if still can be completed within
expected time of completion(33% additional time)
Continue treatment
If less than 80% dose taken and treatment cannot be
completed within additional time RESTART
3 HP Weekly schedule of upto 3 doses
missed
If missed dosed remembered within 2 days complete
If missed doses remembered after 2 days, take the missed
doses immediately and change the schedule for weekly
intake
If between 1-3 doses are missed continue until 12 doses
with extension up to 16 weeks
> 3 weekly doses missed If 4 or more weekly doses are missed RESTART
Poor adherence alternate regimen

39. Treatment completion:
6 H /6Lfx:
80% of recommended dose(144/180)
consumed within 133% planned TPT
duration (239)
3 HP:
80% recommended dose(11/12)
consumed within 133% planned
duration(120 days)
Lost to Follow up:
• TPT interruption by 8 consecutive
weeks(2 months or more for 6 H,6
Lfx )
• 4 consecutive weeks( 1month or
more for 3 HP)

40. Long Term Follow Up- 6, 12, 18, 24 m
• All household contacts of pulmonary TB shall be followed up by the primary
health care team looking for development of active symptoms of TB.
• The same vigil shall continue for all those who were diagnosed with TBI
even after those who completed treatment.
• If any individual initiated on TBI, later develops TB, tests for detecting
resistance to INH and Rifampicin shall be offered at baseline if a biological
specimen is available.

41. Flow of
Events
Identification of Eligible Children – Contact Tracing
Testing for TBI
Rule Out Active TB
Baseline Assessment
Initiation of TBI treatment
Adverse event Monitoring & Ensuring Treatment
Adherence
Monthly Clinical Follow Up
Declaring Treatment Outcome
Long Term Follow Up

42. • 46 year old lady presented with 2 weeks of cough with scanty
expectoration ,Weight loss for the last 6 months. She is diagnosed as
pulmonary TB by sputum NAAT. She resides with 4 year old daughter
14 year old son and 26 year old sister in law who is pregnant along
with her husband(50 year) who is a chronic alcoholic and 70 year old
mother
 What should be the policy for TB prevention treatment in this family
Daughter( 4 year)-Test for TB ,Treat with
3HR
Son(14year) –Test for TB -If negative IGRA
( TBI)
- if IGRA positive 3 HR & if IGRA Negative
no treatment
Sister In law( 26& pregnant) Test for TB -If
negative IGRA ( TBI)
- if IGRA positive 6 H & if IGRA Negative
no treatment
Husband(50)-Test for TB
Test For TBI
Rule out a/c or c/c liver disease
Caution
Mother(70 year)
Test for TB -If negative IGRA ( TBI)
- if IGRA positive 3 HP & if IGRA Negative
no treatment

43. Summary
- DETECT-TREAT-PREVENT-BUILD
- Ruling Out active Disease
- Kerala policy-test& treat
- Current regimens-3 HP,6 H,3HR,6Lfx,4R
- Counsel, treat, monitor