Epidemiology & Management

1. Multi-Drug Resistant Tuberculosis
Dr. Ankit Chaudhary
Resident
Community Medicine
IGMC Shimla

2. TB Magnitude
▪ TB: 9th leading cause of death worldwide
▪ Leading cause from a single infectious agent, ranking above HIV/AIDS
▪ ≈1.3 million deaths in HIV-ve / 374 000 in HIV+ve people (2016)
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3. Global Picture
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4. MDR Problem Statement : Globally
▪ 5% of total TB cases, 3.9% of new cases, 21 % of previously Rx cases
▪ 490,000 estimated (2016)
▪ ++ 110 000 susceptible to INH but resistant to rifampicin (2016)
▪ 47% of global MDR burden in China, India & Russian Federation
▪ ≈ 9.5% of MDR-TB cases have additional DR (XDR-TB).
▪ 117 countries worldwide have reported at least one XDR-TB case
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5. Global response
Burden
• 490 000 people fell ill with MDR-TB in 2016
• Additional 110 000 people with RR TB requiring 2nd-line Rx
Detection
• 132000 cases of MDR TB detected
Treatment
• 125000 started on MDR TB RX
Outcome
• 52% Successful outcome
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6. MDR Problem Statement: India
▪ Prevalence of Rifampicin (R) & MDR-TB in India is around 1,47,000
▪ Translates to around 11 patients/lac population annually
▪ RNTCP Dx & initiated Rx in 34016 MDR-TB & 2476 XDR-TB cases (2016)
▪ 46% had successful Rx outcome
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7. 1st National Anti-TB drug resistance survey (NDRS)
▪ NDRS concluded recently 2014-16
▪ 526 (92.5%) DMCs participated
▪ Quality of specimens collected was good with >97% specimens accepted
▪ 95% patient enrolments were completed within the planned period
▪ Recovery rate for cultures was 94.6% in new & 92.8% in previously Rx pts
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8. DST patterns: National Drug Resistance Survey
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9. MDR Problem Statement : Himachal (2017)
▪ Total 673 diagnosed
▪ 91 died, 36 defaulted
▪ 380 treated
▪ 7 XDR
▪ Kangra was the lead scorer
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10. Vulnerable groups for MDR TB
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11. Case Definition
Presumptive DR TB:
 Failed Rx with 1st line drugs
 Pediatric Non responders
 Contacts of DR TB
 TB Pts found +ve on f/u sputum exam
 Previously Rx TB cases
 TB-HIV Co-infection
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12. RNTCP Criteria – MDR TB
▪ A new smear (+) pt. remaining smear (+) at end of 5th month
▪ A new smear (-) pt. becoming smear (+) at the end of 5th month
▪ A pt. Rx with regimen for previously Rx remaining (+) at 4th month
▪ Smear (+) contacts of an established / confirmed MDR-TB case
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13. Classification on Drug Resistance
▪ MR : Resistance to one 1st line ATB drug only
▪ PDR : Resistance to > one 1st line ATB drug (except both H & R)
▪ MDR : Resistance to at least both H & R
▪ RR : Resistance to R (pheno/genotypic method) with/without
resistance to other drugs excluding H
▪ XDR : MDR plus FQ resistance plus 2nd line injectable resistance
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14. Causes for Resistance
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15. Diagnosis
▪ Lab based
Phenotypic DST (Solid/liquid culture)
OR
Genotypic (LPA/CBNAAT- RNTCP)
 CBNAAT: R LPA: H & R
 Genotypic faster; not growth based
 DST (LJ): 84 days Liq C (MGIT): 42 days LPA: 72 hrs CBNAAT: 2 hrs
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16. Diagnosis contd…..
▪ CBNAAT: Single specimen LPA: Two samples
▪ Wherever facilities available; DST of all drugs intended for regimen
▪ If RR by CBNAAT/LPA
Liq C DST at base line for Levo, Moxi, Kana, Capreo, Ethambutol &
Ethionamide, Linezolid, Pyrazinamide
plus
LPA for INH on sample/culture isolate to decide on INH use
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17. Diagnosis contd…..
▪ If R sensitive (CBNAAT) in presumptive DR-TB cases, samples for LPA/Liq C
▪ INH sensitive Pts. after LPA testing OR awaiting LPA results should continue Rx
▪ If INH Resistance by LPA,
Report must mention KAT G or INH-A mutation
&
Liq C DST for E, Z, Kana, Levo
 If resistance to 2nd line injectables/FQs; DST for remaining 2nd line drugs
 Initiate/Modify Rx as per DST results
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18. Choice of diagnostic technology
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19. DR-TB Diagnostic Algorithm
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20. Pre-evaluation
 Detailed history (screening for mental illness, substance abuse etc.)
 Weight , Height
 Complete Blood Count
 Blood sugar to screen for Diabetes Mellitus
 LFTs/RFTs/TSH
 Urine examination – Routine and Microscopic
 Pregnancy test (for women in child bearing age gp)
 Chest X-Ray
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21. Anti TB Drugs recommended for DR-TB Rx
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22. Standard treatment regimen DR-TB
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23. DST guided regimen with additional resistance
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24. 8/20/2018
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25. 8/20/2018
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guidelines
guidelines

26. Shorter MDR-TB Rx Regimen
Recommended for patients in whom the diagnosis of
▪ MDR/RR-TB has been reliably confirmed by molecular (e.g. CBNAAT/
LPA) or phenotypic DST method
▪ And are found to be sensitive to both FQ and SLI by SL-LPA
▪ Children & PLHIV on ART could receive the shorter MDR-TB regimen
▪ Standardized shorter MDR-TB regimen with 7 drugs & a Rx duration of
9- 11 months
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27. Shorter MDR-TB Rx Regimen contd…..
▪ Total duration is 9-11 months, depending on IP duration
▪ IP should be given for at least 4 months
▪ After 4th month of Rx, if the result of sputum microscopy is -ve then
CP should be initiated
▪ If sputum smear doesn’t become microscopy -ve by the 4th month of
Rx, IP should be prolonged till smear conversion
▪ If IP is prolonged, the injectable agent is only given 3 times/week.
▪ IP should be extended for a max of 2 months (IP is not > 6 months)
▪ Duration of CP is fixed for 5 months
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28. XDR-TB Rx Regimen
▪ Total duration would be of 24-30 months duration with 6-12 months
IP & 18 months CP
▪ The change from IP to CP will be done only after achievement of
culture conversion
▪ IP can be extended on monthly basis from 6 months up to a max of 12
months
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29. Management of Contacts of DR TB
▪ People living in same household as index pt. or spending many hours/day
together with pt. in same indoor space
▪ Should be identified through contact tracing & evaluated for active TB
▪ If contact is found to be suffering from PTB disease irrespective of smear
based MB, s/he will be identified as a Presumptive DR-TB
▪ Initiated on regimen for new/previously Rx pt. based on their previous history
▪ If pt. is confirmed as having DRTB, appropriate DR-TB Rx must be initiated
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30. Newer Anti MDR TB Drugs
▪ Bedaquiline: Blocks an enzyme inside MTB bacteria called ATP
synthase
▪ Recommended dose is 400 mg /day for 2 weeks & then 200 mg taken
3 times/week (with at least 48 hours b/w doses)
▪ Side effects are headache, dizziness, malaise, joint pain, QT
prolongation & increases in liver enzymes
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31. Newer Anti MDR TB Drugs contd…..
▪ Delamanid: Dihydro-nitroimidazooxazole derivative; inhibits synthesis
of cell wall components, methoxy mycolic acid & ketomycolic acid
▪ Dose: 100 mg/day
▪ Side effects are nausea, vomiting and dizziness. Anxiety, pins &
needles, shaking and QT prolongation
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32. Integrated Drug Resistant TB Algorithm
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33. Monitoring
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34. Follow up
▪ Microbiological: One sputum specimen to be collected & examined
by Cx at least 30 days apart from 3rd to 7th month of Rx (end of
months 3,4,5,6,7) & at 3 monthly intervals from 9th month onward till
completion of Rx (9,12,15,18,21,24).
If any Cx during CP or end of Rx is +ve then it should be followed by
monthly Cx for 3 months
 Weight: Monthly
 Chest X ray: At the end of IP, end of Rx & whenever clinically indicated
 Physical Evaluation: Every month for 6 months then every 3 months
for 2 years
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35. Follow up contd…..
▪ S. creatinine: Monthly for first 3 months then every 3 months during
injectable phase
▪ CBC: Weekly in first month, then monthly to rule out bone marrow
suppression
▪ LFT: Monthly in IP & 3 monthly during CP
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36. Extension of Treatment
▪ IP can be extended for max. 3 months (max IP duration-9 months)
▪ In all MDR TB cases with additional DR (including XDR TB), IP can be
extended for max. 6 months (max IP duration-12 months)
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37. Role of surgery in MDR-TB
When U/L resectable disease is present, surgery can be considered for
▪ Absence of clinical/MB response to therapy despite 6-9 months of Rx
▪ High risk of failure/relapse due to high degree of resistance/extensive
parenchymal involvement
▪ Morbid complications like haemoptysis, brochiectasis, empyema
▪ Recurrence of +ve culture status during Rx course
▪ Relapse after completion of ATT
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38. Treatment Outcomes in M/XDR TB
Interim outcomes
▪ Culture conversion: Pt. is considered to have Cx converted when 2
consecutive Cx, taken at least 30 days apart, are found to be -ve.
Specimen collection date of 1st -ve Cx is used as date of conversion
▪ Culture reversion: Pt. is considered to have Cx reverted when, after an
initial Cx conversion, 2 consecutive Cx, taken at least 30 days apart,
are found to be +ve. For purpose of defining Rx failed, reversion is
considered only when it occurs in CP
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39. Treatment outcomes in M/XDR TB contd…..
Final Outcomes
▪ Cured: Rx completed without evidence of failure AND ≥ 3 consecutive
Cx taken at least 30 days apart are –ve after IP
▪ Treatment completed: A patient who has completed Rx according to
guidelines but doesn’t meet definition for cure/failure due to lack of
bacteriological results
▪ Treatment success: Cured + Rx Completed
▪ Treatment failure: Lack of microbiological conversion by end of IP,
reversion in CP, evidence of acquired resistance to FQs/SLID or ADRxn
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40. Treatment Support Program
▪ Include initial & f/u counselling, supervision of Rx, additional
nutritional support, screening of ADR, co-morbidity management
▪ Compensation is provided for transport costs incurred by DR TB
patient for sending specimen for f/u or for travel to DR TB centre
▪ MDR TB Rx supporters get 5000/case for ensuring Rx completion
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41. Model of care in RNTCP PMDT
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42. Drug Resistant TB Centre
▪ 147 DR-TBCs across India (2017), 1/10 million population, including
some private institutes
▪ 5-10 districts attached to each centre
▪ DR-TB pts. admitted for a short period & once stabilized on Rx
discharged & referred back to their districts for continuation &
completion of Rx
▪ Pts. are referred back to DR-TBCs for change of regimens/ ADR Mx
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43. ▪ Since March 2016, 500 CBNAAT machines have been made functional
in addition to 128 existing machines to cover access to most of
districts in India
▪ These machines are currently utilized at district level for testing
presumptive DR-TB patients & presumptive TB patients among key
populations to detect presence of M. Tb in the biological specimen
with concomitant detection of RR-TB if present.
▪ A 35% rise in MDR/ RRTB patients notified was observed in Q2 2016
against Q1 2016 which is expected to further increase in future
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44. National Strategic Plan (2017-25) and PMDT
Objectives
▪ By 2017, complete nationwide geographical coverage of access to
baseline 2nd line DST using SL-LPA, access to shorter MDR-TB regimen
and newer drugs like Bedaquiline
▪ By 2025 ensure Universal access to rapid molecular DRT for all Dx TB
patients; Universal access to DST guided Rx expands access to newer
drugs; and management of NTM
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45. Data management in PMDT
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46. Strategies for Drug Resistant TB
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Strategies
for DRTB
Control
Prevention
of DRTB
DST
guided
Rx
NDR
Survey
Newer
Regimen
Improving
adherence &
Counselling
Nutritional
Assessment
& Sx
Strengthening
procurement
of SLD

47. References
 RNTCP Guidelines Programmatic Management of Drug Resistant TB 2017
 RNTCP Technical and operational guidelines of TB control in India 2016
 National strategic plan for TB elimination 2017–2025
 TB India 2017 RNTCP Annual Status Report
 WHO Global TB report 2017
 WHO MDR TB update 2016
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48. 8/20/2018
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Thank you…..!!!

49. Algorithmic approach to Dx of DR-TB in children
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50. Pre-treatment evaluation of DR-TB (by regimen)
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51. Rx success with shorter MDR-TB regimen vs
conventional MDR-TB regimens
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52. MDR TB with mixed pattern of resistance
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53. MDR TB/RR TB (without additional resistance)
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All MDR TB isolates to be subjected to LC DST at baseline for kanamycin &
Levofloxacin, the results of which are available after 6-8 wks, additional modifications
to be made accordingly

54. MDR/RR TB (with additional resistance)
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55. Dosage of DR-TB drugs for adults
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56. Adverse reactions
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57. Drug boxes for standard DR-TB regimen
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For IP: Type A box + Type B box of same
weight band
For CP: Type A box of same weight band

58. WHO recommended doses of ATT drugs
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