This document provides an overview of tuberculosis (TB) management in India, including: 1) TB burden statistics for India and trends in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases. 2) Guidelines for treatment of drug-sensitive TB, MDR-TB, and XDR-TB including different regimens and drugs. 3) Special considerations for managing TB in vulnerable groups like children, pregnant women, and those with comorbidities. 4) India's adoption of WHO's End TB Strategy to cut TB deaths and cases by 2035.

1. Department of Pharmacology
SVMC, Tirupati.

2. • TB Burden in India
• Incidence of MDR & XDR TB
• Anti TB drugs
• TB Management
• OLD vs New regimens
• Mono/Poly-drug Resistant TB Mx
• MDR TB Mx
• XDR TB Mx

3. • Bedaquiline
• Weight bands – What? How? Why?
• Paediatric TB management
• Mx of other special conditions
• The End TB Strategy
• References...

4. TB Burden in India
• Annually, 1/4th of Global TB Incidence.
• WHO Global TB report – 2.2 million cases.
• 58% reduction in TB mortality rate; 55% reduction in TB prevalence
rate by 2014 as compared to 1990 level
• The TB incidence is on declining trend.

12. Incidence of MDR & XDR-TB
• Over 480 000 cases of multidrug-resistant (MDR) tuberculosis (TB)
occur every year globally
• 9% of them being affected by extensively drug-resistant (XDR)
strains of Mycobacterium tuberculosis.
• In India (2014), an estimated 2.2% of new cases (95% CI: 1.9–
2.6%) and 15% of previously treated cases (95%CI: 11–19%) have
MDR-TB.

13. More than half of the global burden of MDR-TB is in three
countries
• India
• China
• Russia

14. In 2013, the average proportion of MDR-TB cases with
XDR-TB was 9.0%.

15. MDR-TB & HIV+TB Incidence
TB burden Percentage Number (millions)
MDR-TB in Notified PTB 0.071
MDR-TB in New Notified PTB 2.2% 0.024
MDR-TB in Re-Rx PTB 15% 0.047
HIV in Incident TB cases 5%

16. Anti TB Drugs

18. New Anti TB drugs
• Bedaquiline
• Delamanid
• Pretomanid
• NC-002, NC-003
• Sutezolid
• SQ 109
• Benzothiazinones

19. Repurposed Anti TB drugs
• Linezolid
• Clofazamine
• Imipenem/ Meropenem
• Amoxicillin – Clavulanate
• Thioacetazone
• Clarithromycin

20. TB Management

21. Cases
Microbiologically
confirmed TB Case
Clinically diagnosed
TB case
Anatomical site TB Rx History Drug resistance
Pulmonary TB
Extra Pulmonary TB
New case
Previously treated
Transferred in
MR
PDR
MDR
XDR
RR
Recurrent Rx after
Failure
Rx after loss to
follow up
Others
Miliary
TB

27. Old vs New (2016) Regimens

28. Rx of Drug sensitive TB:
Till 2015 2016
Thrice weekly regimen Once daily for all Paediatric & PLHIV
cases – 104 districts
Individual drug doses based on 3
weight bands for MDR TB Rx
FDCs based on weight bands (4 in
adult, & in child) for TB Rx
Continuation of IP for 1 month if
sputum positive
IP need not be continued
CP is with HR CP includes Ethambutol (HRE)
For EP Tb cases, CP is for 7 mo For EP TB cases, CP is extended for
12-24 wks (3-6mo)
For TBM cases Inj SM added in IP No change in IP

29. 104 districts in 5 states
• Maharashtra
• Bihar
• Kerala
• Sikkim
• Himachal Pradesh

30. Mono/Poly-drug Resistant TB Mx
• IP can be extended for maximum 3mo.

31. RR/MDR TB Mx
Drugs given are -
• Kanamycin
• Levofloxacin
• Ethionamide
• Pyrazinamide
• Ethambutol
• Cycloserine

33. • For MDR TB cases, IP can be extended for 3mo maximum
• For all MDR TB cases with additional resistance, IP can be
extended for maximum 6mo.

34. In case of additional resistance,
• Resistance to E – Omit E
• Resistance to P – Omit P
• Res to P&E – Add PAS in IP & CP
• Res to Lfx/Mfx – use PAS + the sensitive one among them
• Res to Lfx&Mfx – Clfz, Lz, PAS in IP&CP(6-12mo)
• Res to any SLI – use the sensitive one
• Res to all SLI - Clfz, Lz, PAS in IP&CP(6-12mo)

36.  Cure: Completed treatment but consistently culture -ve (with at least
5 consecutive negative results in the last 12 to 15 months). If one follow-
up +ve culture is reported during the last three quarters, patient will still be considered cured
provided this positive culture is followed by at least 3 consecutive negative cultures, taken at least
30 days apart, provided that there is clinical evidence of improvement.
 Treatment completed: A patient who has completed treatment
according to guidelines but does not meet the definition for cure or
treatment failure due to lack of bacteriological results.
 Treatment failure: If >2 of 5 cultures recorded in the final 12-15
months are +ve, or if any of the final three cultures are +ve.
 Treatment default: A patient whose treatment was interrupted for 2
or >2 consecutive months for any reasons.

37. XDR TB Mx
Drugs given are –
• Capreomycin
• Moxifloxacin
• Linezolid
• PAS
• Clofazamine
• Amoxi/Clav
• High Dose INH

38. Management Guidelines for Patie nts with Documented
or Strongly Suspecte d Extensively Drug-Resista nt
Tuberculo sis (XDR-TB)
1. Use pyrazinamide and any first-line oral agents that may be
effective.
2. Use an injectable agent to which the strain is susceptible, and
consider
an extended duration of use (12 months or possibly the whole
treatment
period). If the strain is resistant to all injectable agents, use of one
that the patient has not previously received is recommended.a
3. Use a later-generation fluoroquinolone, such as moxifloxacin,
high-dose
levofloxacin, or possibly gatifloxacin.b
4. Use all second-line oral bacteriostatic agents (para-aminosalicylic
acid,
cycloserine, and ethionamide or prothionamide) that have not been
used extensively in a previous regimen or any such agents that are
likely
to be effective.
5. Add bedaquiline or delamanid and one or more of the
following drugsc:
clofazimine, linezolid, amoxicillin/clavulanic acid, clarithromycin,
and carbapenems
such as imipenem/cilastatin and meropenem.
6. The simultaneous use of bedaquiline and delamanid is not
recommended
at the moment in view of the current lack of information on the
potential
of adverse reactions when these drugs are administered
together.
7. Consider treatment with high-dose isoniazid if low-level
resistance to this
drug is documented.
8. Consider adjuvant surgery if there is localized disease.
9. Enforce strong infection-control measures.
10. Implement strict directly observed therapy and full adherence
support as
well as comprehensive bacteriologic and clinical monitoring.

39. TDR TB
• No specific management guidelines mentioned by WHO/ RNTCP.

40. Mixed resistance TB

41. Bedaquiline (BDQ)
• New class of drug - Diarylquinone.
• Specifically targets Mycobacterial ATP Synthase.
• Strong Bactericidal and sterilizing activity.
• June 2013 – WHO published Interim policy guidance for use of BDQ
in conjunction with WHO recommended MDR-TB STRs.
• 2016 – RNTCP is introducing BDQ through conditional access
programme at 6 sites in India.

42. Criteria to receive BDQ (Apex Committee):
• Adults >18y with PTB
• Non pregnant females using non-hormonal birth control methods.
• Absence of arrhythmias or Controlled stable arrhythmias.

43. Weight bands... What? How? Why?
• Recommendation of drug doses according to weight have been
made since 2010 itself.
• New (2016) guidelines by Govt of India Central TB Division provides
number of FDCs according to weight bands.
• 4 weight bands for Adults, 7 for children.
• This is to prevent further drug resistance and assured bioavailability
by increasing drug compliance.

47. Paediatric TB Mx

48. • Children represent about 10-11% of all TB cases.
• In 2014, 81 000 children died of TB, and there were an additional 55
000 TB deaths among children who were HIV-positive.
• TB in children can be treated. Most children tolerate treatment very
well.
• Preventive therapy is highly effective in children exposed to TB.
• Simple, child-friendly fixed-dose formulations are easy to administer
and match WHO dosage recommendations for first line treatment.

50. • STRs to drug sensitive and MDR TB for paediatric age
group are similar to adult, with dose changes.
• INH Preventive therapy for <6y age children who are
– Close contacts of TB
– Excluded to have active TB
• Irrespective of BCG and nutritional status.
• INH 10mg/kg for 6mo given.

51. Mx of Other Special conditions

52. TB in Pregnancy

53. TB in seizure pts
• Prophylactic Pyridoxine (Vit B6):
– On INH – 10-25mg/d
– On Cycloserine – 25mg/250mg cycloserine.
• In DR TB cases with H/O seizures, avoid
– Cycloserine
– Ethionamide
– Fluoroquinolones

54. TB in Psychosis pts
• Psychosis Rx, Individual counselling, Group therapy, along with TB
management are essential.
• Avoid Ethionamide & FQs.
• No absolute C/I for Cycloserine, though it may cause severe
psychosis and depression.Only temporary suspension advised.
• Prophylactic Pyridoxine is helpful.

55. TB with Liver disorders
• Usual STRs for
– Past h/o active hepatitis
– H/o alcohol intake
– Hepatitis virus carriage
– No evidence of chronic liver disease
• LFTs to be done at treatment initiation for patients with
unstable or advanced liver disease.

56. If serum alanine aminotransferase is 3 times more than that
at treatment initiation,

57. DR TB in Liver disease pts:
• PZA, PAS & Ethionamide – Potentially hepatotoxic.
• Most of second line drugs are safer than first line drugs in mild
hepatic impairment.
• Avoid P & E.
• If hepatic reactions occur even to second line drugs, consider &
evaluate other causes.

58. End TB Strategy

59. • WHO’s End TB Strategy
The strategy aims to end the global TB epidemic, with targets to
reduce TB deaths by 95% and to cut new cases by 90%
between 2015 and 2035, and to ensure that no family 100% is
burdened with catastrophic expenses due to TB.

60. References
• http://tbcindia.nic.in Central Tuberculosis Division, Govt Of India.
• WHO website http://www.who.int/tb/en/
• Goodman & Gilman, The Pharmacological basis of Therapeutics
12th Ed.
• K.D. Tripathi, Essentials of Medical Pharmacology, 7th Ed.
• Harrison’s Principles of Internal Medicine 19th Ed.