Sensitization Program for Medical College Facilities on NTEP

1. Moving towards END TB in
India: Where we stand and
where to go !
Dr Abhijit Dey- WHO NTEP Consultant
M- 9433441835 Email- deya@rntcp.org

2. Where we stand?

3. TB Epidemiology –India 2019-2021
Source: WHO Global TB Report 2016, 2020, 2021 & 2022
Parameters 2015 2019 2020 2021
Estimated TB incidence 28,40,000 26,40,000 25,90,000 29,50,000
Incidence per 100 000
population 217 193 188 210
Total TB Deaths 4,19,000 4,45,000 5,04,000 5,05,000
TB case fatality ratio
(estimated
mortality/estimated
incidence) 15% 17% 20% 17%
Total cases notified 17,40,000 23,91,022 18,12,643 21,16,976
Missed cases / Gap in
notification
11 lakhs
(missing
million) 248978 777357 833024
% Missed case 39% 9% 30% 28%

4. Where to go?

5. Few Public-health targets set by WHO
Eradication (zero transmission at global level)
• Polio
• Dracunculiasis (Guinea worm disease)
• Yaws
Elimination (interruption of active transmission at country level)
• Onchocerciasis
• Human African trypanosomiasis (g)
Elimination as a public-health problem (elimination of morbidity, mortality and/or reduction of
transmission)
• Tuberculosis
• Human African trypanosomiasis (r)
• Chagas disease
• Lymphatic filariasis
• Rabies
Control (reduction of morbidity)
• All the others
• Trachoma
• Visceral leishmaniasis
• Schistosomiasis
• Soil-transmitted
helminthiases
• Leprosy
• Malaria

6. Where to go: India’s Commitment to End TB
Vision: India free of TB
TARGETS (for
Reduction)
INDIA (NSP) SDG WHO
End TB
2025 2030 2035
Reduction in number of TB deaths
Compared with 2015 (32 deaths per 1 lakh )
90%
(3 per lakh)
90% 95%
Reduction in TB incidence rate
Compared with 2015 (217 cases per 1 lakh)
80%
(44 per lakh)
80% 90%
Family affected with catastrophic costs
due to TB
100%
(0)
100% 100%

7. How to go: Updates on the 4 pillars of the National Strategic Plan
(2020-25)
Treat
Prevent
Build
Detect
• Presumptive TB testing 2400 per lac per
year
• Quality TB Testing- Newer Rapid molecular
tests
• Vulnerability mapping- Targeted ACF
• Integrated ACF-TPT campaign
• Shorter DSTB , DRTB & Pediatric TB
Regimens
• PMTPT scale up
• Airborne infection control
• Integrated ACF TPT campaign
• TBI Testing
• TB Vaccine
• Community empowerment involving
Satkeholders , volunteers, healthworker &
cured TB patients (TB Champions)
• PMTBMBA- Pradhanmantri TB Mukt
Bharat Abhiyan (Nikshay Mitra)
• Training & Capacity building
• Research & Innovation

8. Updates on: Detect
Detect

9. • Detects mutations associated with resistance
towards H, FQ, SLI & Eto in a single test.
• Uses a semi quantitative nested PCR followed
by high resolution melt technology.
• The test can run on GeneXpert platforms
equipped with 10-colour modules
• Results are available in 90 minutes.
• The test has been evaluated by WHO (Rapid
Communication- January 2021).
• The newer Xpert MTB/RIF Ultra cartridge has
shown improved sensitivity in recent field
trials, but at the expense of reduced
specificity. A significant proportion of “trace”
results are false positive in high burden set up.
• Yet to be endorsed by GOI
Drug resistance Target region
Isoniazid inhA promotor, katG,fabG1,
oxyR- ahpC intergenic region
Ethionamide inhA promotor
Fluoroquinolone gyrA, gyrB
Amikacin, Kanamycin,
Capreomycin
rrs, eis promotor
9
Drug
resistance
Vs phenotypic DST Vs sequencing
Sensitivity
(%)
Specificity
(%)
Sensitivit
y (%)
Specificity
(%)
Isoniazid 91.4 99.1 98.8 98.7
Fluoroquinolo
ne
93.1 98.5 93.3 100
Amikacin 91.9 99.4 96.4 100
Kanamycin 87.9 99.6 96.7 100
Capreomycin 84.0 100 96.3 100
Ethionamide 64.7 98.3 97.2 100
Xpert MTB/XDR

10. • Studies demonstrated the impact of these NGS technologies on improved DR-
TB patient diagnosis and treatment outcomes will also be critical.
• Five WGS platforms (Illumina Miseq.), and one Pyrosequencer (Quaigen,
PyroMark 48) have been deployed at National and State-level TB Laboratories.
These will initially be used for sentinel surveillance of drug resistance.
• Amplification-based targeted NGS assays for detecting DR-TB directly from
sputum specimens are in the pipeline and being used in private sector. These
assays have not yet been reviewed or approved by WHO & GOI.
10
Genetic sequencing

11. Updates on : Treat
Treat

12. Treatment success rate of M/XDR-TB : Where we stand
46% 47% 45% 47% 48% 49%
52%
57%
65%
32%
24%
28% 28%
31%
34% 45%
53%
59%
72%
78%
83%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
2012 2013 2014 2015 2016 2017 2018 2019 2020
TO of MDR-TB patients TO of XDR-TB patients* Hr-TB regimen
Introduction of Bedaquiline
containing regimen
Introduction of longer
oral M/XDR-TB
* 2016 onwards XDR-TB cohorts include patients treated with Bedaquiline containing regimen.
Introduction of Shorter
MDR-TB regimen
Jan-Jun 2020 cohort

13. 1. The 6-month BPaLM regimen, comprising bedaquiline,
pretomanid, linezolid (600 mg) and moxifloxacin, may be
used programmatically in place of 9-month or longer (>18
months) regimens, in patients (aged ≥15 years) with
MDR/RR-TB who have not had previous exposure to
bedaquiline, pretomanid and linezolid (defined as >1 month
exposure).
2. This regimen may be used without moxifloxacin (BPaL) in
the case of documented resistance to fluoroquinolones (in
patients with pre-XDR-TB).
• Drug susceptibility testing (DST) to fluoroquinolones is
strongly encouraged, but DST should not delay treatment
initiation.
• BPaL, Bpal-M & BpalC is being evaluated in few
states under programmatic conditions.
WHO Rapid communication on the treatment of DR-TB (1)

14. • People aged 12 years or older with drug-
susceptible pulmonary TB, may receive a 4-month
regimen of isoniazid, rifapentine, moxifloxacin and
pyrazinamide
• This regimen is yet to be endorsed by GOI
WHO recommendation on DS-TB

15. • In children with MDR/RR-TB aged below 6 years, an all-
oral treatment regimen containing Bedaquiline may be
used
• In children with MDR/RR-TB aged below 3 years
Delamanid may be used as part of longer regimens
• In children and adolescents between 3 months and 16
years of age with non-severe TB (without suspicion or
evidence of MDR/RR-TB), a 4-month treatment
regimen (2HRZ(E)/2HR) should be used
• In children and adolescents with bacteriologically
confirmed or clinically diagnosed TB meningitis
(without suspicion or evidence of MDR/RR-TB), a 6-
month intensive regimen (6HRZEto) may be used as an
alternative option to the 12-month regimen
(2HRZE/10HR)
• These are yet to be endorsed by GOI
WHO recommendation (Paediatric - TB)

16. Updates on : Prevent
Prevent

17. PMTPT policy related update
PMTPT policy Update
Target
population
Household contacts of
pulmonary TB*
Expansion of target population
PLHIV
Coverage to improve
Other risk groups - dialysis,
silicosis, initiated on
Immunosuppresant or anti-
TNF, translplant receipients
NTEG meeting (23-24 Sep 2022)
Malnourished, Alcohol abusers, smokers and
diabetics
TPT intervention to be merged with ACF and
community level intervention

18. PMTPT policy related update
PMTPT policy Update
Testing
option
IGRA or TST
• IGRA or TST or Cy*-TB
• DCGI approval for use of Cy-TB in age
>/=18 years
• ICMR study is ongoing to validate
feasibility of Cy-TB in age <18 years [likely
to get approval from DCGI following study
findings by year end]
NTEG recommendations:
Procurement of estimated requirement of 104.34 lakh TBI testing (Cy-Tb) and 100.32 lakh TPT
courses (3HP) for 2 years as per current TPT policy
*Cy stands for Dr Cyrus Poonawalla, the founder of Serum Institute of India Pvt. Ltd. (SIIPL) which is the producer & distributor of the test.

19. Cy- TB Background
• Cy-TB is the next-generation skin test for detection of Tuberculosis.
 Easy-to-use (Simple)
 Point-of-care (On field)
 Specific test(based on ESAT-6 and CFP-10 antigens of M.tb)
• Cy-TB is:
 Unaffected by BCG vaccination status
 Easy Replacement for PPD (TST) test

20. TB VACCINE CANDIDATES
I
PHASE
II a
PHASE
II b
PHASE
III
PHASE
AdHu5Ag85A McMaster,
CanSino
AEC/BC02 Anhui Zhifei
Longcom
ChAdOx185A-MVA85A
(ID/IM/Aerosol)
University of Oxford
TB/FLU-04L
RIBSP
ID93 + GLA-SE
IDRI, Wellcome Trust,
IAVI
BCG ReVax
Gates MRI
DAR-901 booster
Dartmouth, GHIT
H56: IC31
SSI, Valneva, IAVI
M72/AS01E
GSK, Gates MRI
RUTI®
Archivel Farma, S.L.
VPM1002
SIIPL, VPM
MIP/Immuvac
ICMR, Cadila
Pharmaceuticals
MTBVAC
Biofabri, TBVI,
University of Zaragoza
GamTBvac
Ministry of Health,
Russian Federation
Viral vector
Live
Protein / Adjuvant
Whole cell / Extract
https://www.who.int/publications/digital/global-tuberculosis-report-2021/research-innovation
I
PHASE
II a
PHASE
II b
PHASE
III
PHASE

21. BCG vs rBCG
BCG
vs
rBCG
BCG Vaccine
• The attenuation of BCG achieved by passaging
virulent M. bovis for 13 years in the laboratory.
• Crucial genetic changes occurred which resulted in
loss of genes required for generating specific
immune responses required for complete protection
• Loss of genes for Stimulation of MHC Class I
pathway thereby offering only partial protection
rBCG Vaccine
• Original BCG altered with inclusion of
listeriolysin O and deletion of urease C genes
• This is for enabling for stimulation of both CD4
& CD 8 mediated T cell immunity which
expected to offer better protection
MHC class I and II antigen presentation pathway can stimulate CD4+ and
CD8+ T-cell subsets, respectively, both of which are required for optimal
protection against TB.

22. Clinical experience
Potential of BCG in other indications – Trained immunity
• BCG boost can protect against other infectious & inflammatory diseases
• Reduction of childhood mortality – Aaby et al. J Infect Dis. 2011
• Non-specific effects: epigenetic and metabolic reprogramming of innate immune cells  “trained immunity” – Netea
et al. Cell Host Microbe. 2011
• Reduction of the incidence of respiratory tract infections – de Castro et al, Clin Infect Dis 2015
• Exertion of antiviral effects in experimental models, especially by induction of IL-1β – Moorlag et al. Clin Microbiol Infect.
2019
• Reduction of viremia in an experimental human model (yellow fever virus) – Arts et al. Cell Host Microbe. 2018
• Phase III (elderly population in Germany in the indication of trained immunity)
Demonstration of potential beneficial effects of VPM1002 by observing a reduction in respiratory infections in
general and of the COVID-19 disease severity in high-risk populations such as elderly people
• Ongoing Phase I/II (adults in Switzerland/Germany in the indication of bladder cancer)
Evaluation of safety and efficacy of intravesical instillation of rBCG/VPM1002BC in patients with recurrent
non-muscle invasive bladder cancer after transurethral resection of the bladder and standard BCG therapy

23. ALGORITHM FOR TPT & BCG VACCINE
HH contact
aged >18+
Test with
IGRA/TST/CyTB
Positive
TPT
Negative
BCG
vaccination
Rule out active
TB
3 months post Rx

24. Operationalization of the diagnostic
and treatment activities of TB in
Medical College and Nikshay entry

25. Case Finding: Patient Flow- at the OPD
• Presumptive TB should be identified & referred from all OPDs.
Overall referral rate of a MCH should be at least 3 % of total OPD
footfall (5% of new adult footfall)
• Micro-biological confirmation to stressed upon. Expert’s bias usually
leads to significant over diagnosis of DSTB & under diagnosis of
DRTB
• ICF to be done at ART center, TCC, NCD clinic, MCH clinic. Referral
register should be maintained
• To minimize attrition- all identified presumptive cases may be
enrolled in Nikshay using Ni-khay portal (needs ID password) or TB
Arogya Sathi Apps (no need of ID password)

26. Case Finding: Patient Flow-indoor patients
• ICF may be conducted among all admitted patients. Findings/Yield may be
reported / disseminated through NTEP OR
• Presumptive TB patient should complete necessary investigations in IP ward
• Patient diagnosed with TB
– Initiate treatment while in IPD with proper AIC (Isolation ward/room). FDC s to
be made available in all wards
– For DR TB patients drugs should be made available in respective DRTB center in
each medical college

27. – All Diagnosed TB Patient should be counseled, offered HIV test, test for
diabetes
– Patient should be given medicine for one week/10 days for
consumption during transit
– Critical case management- Differentiated care / ITU set up
– Ni-kshay entry on treatment initiation and subsequent transfer out to
be done/facilitate.
– Service provider should document all the service given at their level
using Nikshay.
– Nikshay portal also should be used for monitoring , evaluation &
research.
Case Holding at MCH

28. Thank You