TB new guidelines

1. Recent Changes in Technical and
Operational Guidelines for
Tuberculosis Control Programme in India –
2016: A Paradigm Shift
in Tuberculosis Control
DR.Y.JEGAN MOHAN

3. INTRODUCTION
 1962 - The national tuberculosis programme of India (NTP) was initiated - for domiciliary
treatment, using self-administered standard drug regimen.
 1992 - the Government of India with World Health Organization (WHO) and Swedish
International Development Corporation Agency (SIDA) reviewed the tuberculosis (TB)
situation and the performance of NTP revealing its flaws.
 1997, Revised TB Control Programme (RNTCP) was launched & adopted the Directly
Observed Short Course (DOTS) strategy which was the most systemic and cost-effective
approach to revitalize the TB control programme in India.

4. OBJECTIVES OF RNTCP
 To achieve at least 85% cure rate among the new smear-positive cases initiated
on treatment and thereafter a case detection rate of atleast 70% of such cases.
MAJOR ADDITION TB UNIT (SUB-DISTRICT SUPERVISORY
UNIT)
RNTCP Supervisor
TB UNIT with decentralized diagnostic services
DOTS Provider (DP)
 First technical & operational guidelines was initiated in the early years – updated on 2005
 Web-based TB notification system for notification from both public and private sectors.
(NIKSHAY)

5. RNTCP National strategic plan for TB
Control 2012-2017
 Goal – Universal access of quality of TB diagnosis and treatment of all TB patients in
community.
 Objectives :
 1. To achieve 90% notification rate for all cases
 2. To achieve 90% success rate for all new and 85% for re-treatment cases
 3. To significantly improve the successful outcome of treatment for DRTB cases
 4. To achieve decreased morbidity and mortality for HIV-associated TB cases
 5. To improve the outcome of TB care in the private sectors.
 A government order issued by the Government of India in May 2012 mandates all health care
providers to notify every TB case and/or treated to the local authorities.

6. Organization structure of RNTCP
 1 TB Unit per 5 lakh population 1 TB Unit per block / 1.5–
in urban areas 2.5 lakh population in
 1 per 2.5 lakh in tribal, hilly urban areas
and difficult areas.

7. PRESUMPTIVE TB CASES
PULMONARY TB SUSPECT PRESUMPTIVE PULMONARY TB
• Individual having cough for 2 weeks or
more
• Contacts of smear positive TB patients
having cough for any duration.
• Suspected / conformed extra
pulmonary TB having cough for any
duration.
• HIV positive patients having cough for
any duration.
 Cough > 2 weeks
 Fever > 2 weeks
 Significant weight loss
 Hemoptysis
 Any abnormalities in chest radiography.
- Contact of microbiologically confirmed
TB patients, PL HIV, diabetics,
malnourished, cancer patients, patients on
immunosuppressive therapy or steroids
regularly screened.

8. Other definition changes
 No change in definition of presumptive extra-pulmonary TB cases.
 Presumptive TB cases in paediatric patients
 Loss of >5% body weight as compared to highest weight recorded in last 3
months.
 History of unexplained or no weight gain in the past 3 months.
 Symptomatic child contact with any form of active TB in last 2 years.

9.  Presumptive DRTB cases :
 TB patients failed treatment with first-line anti-tubercular drugs,
 Paediatric TB non-responder.
 TB patients who are contacts of DRTB.
 TB patients who are found positive on any follow-up sputum smear
examination during treatment with first-line ATD.
 Previously treated TB cases.
 TB patients with HIV co-infection.

10.  SMEAR EXAMINATION – SPOT EARLY MORNING OR SPOT-SPOT TEST
 CBNAAT – CARTRIDGE BASED NUCLEIC ACID AMPLIFICATION TEST
 PLHIV – PATIENTS LIVING WITH HIV
 PMDT – PRESUMPTIVE MULTIDRUG RESISTANT TB
 LPA – LINE PROBE ASSAY

12.  TST - Targeted Tuberculin Skin Testing

13. CASE DEFINITION
 MICROBILOGICALLY CONFIRMED TB – Presumptive TB patient with
histological specimen
 positive for acid-fast bacilli or
 positive for MTB on culture or
 positive for TB through Quality Assured Rapid Diagnostic molecular test.
 CLINICALLY DIAGNOSED TB - Presumptive TB patient who is not
microbiologically confirmed but has been diagnosed with active-TB by a
clinician on the basis of X-ray abnormalities, histopathology or clinical
signs with a decision to treat the patient with a full course of anti-TB
treatment.

14. CLASSIFICATION OF TB
 MICROBILOGICALLY CONFIRMED OR CLINICALLY DIAGNOSED TB are
classified according to :
1. Anatomical site of disease
2. History of previous TB
3. Drug resistance

15. DEFINITION CHANGES UNDER HISTORY
OF PREVIOUS TB CLASSIFICATION
 New case – A TB patient who has never had treatment for TB or has taken ATD for <1 month. (No change in new
guidelines.)
 Previously treated patients have received one month or more ATD in the past.
This may be:
 (a) Recurrent TB case – A TB patient previously declared as successfully treated (cured/treatment completed) and
who is subsequently found to be microbiologically confirmed TB case is a recurrent TB case. (Previously called
relapse.)
 (b) Treatment after failure – Patients are those who have previously been treated for TB and whose treatment failed
at the end of their most recent course of treatment. (Previously, it was called failure where a TB patient is
sputum-positive at 5 months or more after initiation of treatment.)
 Treatment after loss to follow-up – A TB patient previously treated for TB for one month or more and who was declared
lost to follow-up in their most recent course of treatment and subsequently found microbiologically confirmed TB cases.
(Previously called treatment after default – a patient who has received treatment for TB for a month or more from any
source and return for treatment after having defaulted, that is, not taking ATD consecutively for 2 months or more and
found to have smear-positive.)

16. DEFINITION CHANGES UNDER DRUG
RESISTANCE CLASSIFICATION
 Mono resistance (MR) – TB patient whose biological specimen is resistant to one
first-line anti-TB drug only.
 Poly resistance (PDR) – A TB patient whose biological specimen is resistant to more
than one first-line anti-TB drug, other than both INH and Rifampicin.
 Multi-drug resistance (MDR) – A TB patient whose biological specimen is resistant to
both INH and Rifampicin with or without resistance other first-line ATD, based on
results from a Quality Assured Laboratory. (No changes.)
 Rifampicin resistance (RR) – Resistance to Rifampicin detected by phenotypic or
genotypic methods with or without resistant to other ATD excluding INH. Patient with
RR should be managed as if they are in MDR TB case.
 Extensive drug resistance (XDR) – MDR TB case whose biological specimen was
resistant to a Fluroquinolone (FQ) and a second-line injectable ATD from a Quality
Assured Laboratory. (No changes.)

17. DRUG REGIMEN – DRUG SENSITIVE TB
PREVIOUS GUIDELINES NEW GUIDELINES
• Standard intermittent
regimen with 2 categories
of treatment
• Treatment under direct
observation of DP
• Category decided by MO
(category I/II)
• Drugs to be taken three
times a week under direct
observation of the DP
• Intensive phase (IP) for 2–3
months – all doses given
under supervision
• Continuation phase (CP)
for 4–5 months – first dose
of the week given under
supervision.
NEW TB CASES :
• Treatment in IP will consist
of 8 weeks of INH,
Rifampicin, Pyrazinamide
and Ethambutol in daily
dosages as per four weight
bands categories
• There will be no need for
extension of IP
• Only Pyrazinamide will be
stopped in CP while the
other three drugs will be
continued for another16
weeks as daily dosages.
NEW GUIDELINES
PREVIOUSLY TREATED CASES :
• IP will be of 12 weeks, where
injection Streptomycin will be
stopped after 8 weeks and the
remaining four drugs in daily
dosages as per weight band for
another 4 weeks.
• No need of extension of IP.
• At the start of CP, Pyrazinamide will
be stopped while rest of the drugs
will be continued for another 20
weeks as daily dosages.

18. EXTRAPULMONARY TB MANAGEMENT
New guidelines :
 The CP in both new and previously treated cases may be extended 3–6
months in certain TB such as CNS, skeletal, disseminated TB, and so on
based on clinical decision of the treating physicians
 Extension beyond 3 months will only be on recommendation of experts of
concerned field. (In the previous guidelines, extension of ATD in case of
CNS and skeletal TB was maximum 3 months).

19. Fixed dose combination – daily doses

20. FOLLOW UP – NEW GUIDELINES
 Clinical follow-up – (new addition)
 Should be at least monthly
 Follow-up laboratory investigation
 For PTB cases – sputum smear examination at the end of IP and at the end of
treatment. (In the previous guidelines, follow-up sputum smear to be done at 2, 4 and
6 months for new cases and 3, 5 and 8 months in previously treated cases.)
• In case of clinical deterioration, the Medical Office may consider repeat sputum smear even
during CP. (New addition.)
• At the completion of treatment, sputum smear and culture should be done for every patient
• CXR – to be offered whenever required and available.
 Long-term follow-up
 After completion of treatment, the patient should be followed up at the end of 6, 12,
18 and 24 months. Any clinical symptoms and/or cough, sputum microscopy and/or
culture should be considered. (New addition) However, there was no provision of
long-term follow-up in the previous guidelines.

21. TREATMENT OUTCOMES - DEFINITIONS
 Cured
 A microbiologically confirmed TB at the beginning of the treatment who was smear- or culture-negative at the end of
complete treatment. (Changed).
 Treatment success
 TB patients either cured or treatment completed are accounted in the treatment success. (New addition).
 Failure
 A TB patient whose biological specimen is positive by smear or culture at the end of the treatment. (Changed).
 Failure to respond
 For paediatric TB patients. (New addition).
 Lost to follow-up
 A TB patient whose treatment was interrupted for one consecutive month or more. (New addition).
 Not evaluated
 A TB patient for whom no treatment outcome is assigned. (Former transfer out).
 Treatment regimen changed
 Previously, it was called as switched over to MDR treatment.

22. Management of TB patients with liver
disorder
 If the serum alanine amino transferase level is more than three times normal before
initiation of treatment, the regime should be:
 (1) Containing two hepatotoxic drugs:
 INH + Rifampicin + Ethambutol for 9 months
 or
 INH + Rifampicin + Ethambutol + Streptomycin for 2 months followed by INH and Rifampicin
for 7 months
 or
 Rifampicin + Ethambutol + Pyrazinamide for 6–9 months.
 (2) Containing one hepatotoxic drug:
 INH + Ethambutol + Streptomycin for 2 months followed by INH + Ethambutol for 10 months.
 (3) Containing no hepatotoxic drugs:
 Streptomycin + Ethambutol + FQ for 18–24 months.

23. Isoniazid Preventive Therapy (IPT)
for PLHIVs
 (a) Adult and adolescents living with HIV should be screened for TB and
those who are unlikely to have active TB should be offered IPT
 (b) Children with HIV who have no TB symptoms and who are unlikely to
have active TB on symptom-based screening should be offered IPT
regardless of their age
 (c) All children with HIV who have successfully completed treatment for TB
disease should receive IPT.
 Dosage of INH preventive therapy:
 Adult and adolescent: INH 300 mg + Pyridoxine 50 mg per day for 6 months.
 Children above 12 months: INH 10 mg/kg + Pyridoxine 25 mg per day for 6
months.

24. ART IN RELATION TO ATD

25. CHANGES IN DRTB (DRTB
GUIDELINES)
 • Bedaquiline (BDQ):
 New class of drug, diarylquinoline that targets mycobacterial ATP synthase, and
enzyme essential for supply of energy to mycobacterium TB
 Strong bactericidal and sterilizing activities against MTB
 It has no cross-resistance with first- and second-line ATD
 Significant benefit in improving the time to culture conversion in MDR TB
patients
 RNTCP introducing BDQ at six sites in the country initially
 Basic criterion – Adult aged ≥18 years having pulmonary MDR TB
 Female should not be pregnant.

27. MDR/RR TB cases (without additional
resistance)
 Treatment regimen for MDR TB
contains 6–9 months of IP with
Kanamycin, Levofoxacin, Ethambutol,
Pyrazinamide, Ethionamide and
Cycloserine and 18 months of CP with
Levofoxacin, Ethambutol,
Ethionamide and Cycloserine (no
change).
 But if INH resistance is not known or
DST result shows sensitivity to INH,
then addition of INH in the
above-mentioned regimen of ATD is
to be done. (New addition)

28. MDR/RR TB cases (without additional
resistance)
 All MDR TB cases would be subjected to LC and DST at baseline for
Appropriate modification of the treatment regimen can be done in case
of additional resistance.
 If isoniazid resistance is found, the use of isoniazid depends on:
 1. If high-level resistance detected by liquid culture – omit INH.
 2. If low-level resistance detected by LC – add high dose INH.
 3. If LPA reports INH resistance by Kat G mutation – omit INH.
 4. If LPA reports INH resistance by INH A mutation – add high dose INH.

29. MDR/RR TB cases (without additional
resistance) (New additions)
 If RR by CBNAAT, then add INH in the standard dose till result of LPA or LC and DST.
 For new patients diagnosed as TB and RR by CBNAAT – repeat CBNAAT and send the sample for
liquid culture
 If second CBNAAT shows RR then start standard MDR till result for culture DST available. Perform DST to
INH and SLDST on liquid culture.
 If second CBNAAT shows R sensitiveness, continue regimen for new TB cases and wait for LC and DST. As
soon as LC result is available, modify the regimen as follows:
 If LC shows R sensitiveness – continue regimen for new TB cases
 If LC shows R resistance – refer the patients to DRTB centre for decision regarding starting MDR or continuing
regimen for new TB cases depending on the response to treatment given so far.
 For mixed resistance pattern, consider oral drug in the sequence of preference – Pyrazanamide,
Ethambutol, Ethionamide, Cycloserine, Para-Aminosalicylate Sodium (PAS), Clofazimine,
Linezolide, Coamoxyclave, high dose INH, Clarythromycin
 Regimen designing or modification will be prerogative of the DRTB centre committee only.

30. MONO OR POLY DRUG RESISTANCE
TREATMENT
 Mono drugs resistance TB.
 Injectable second-line drug (SLD) + FQ + Rifampicin
+ two out of the first-line drugs (from H, E, Z) to
which the patient is sensitive to make a total five
effective drugs given daily.
 In case of reported baseline additional resistance to
other first-line drugs (FLD) the regime is – injection
SLD + FQ + Rifampicin + any FLD to which the
patient is sensitive + one of the remaining group
four drugs (Ethionamide, Cycloserine, PAS)
 In addition, high dose INH is to be added if LPA
shows inhA mutation or culture shows low-level
INH resistance
 Total duration of treatment will be 9–12
months
 IP for 3 months with extension to a
maximum 6 months and CP for 6 months
depending on follow-up sputum reports
 Treatment initiated at DRTB centre.

31.  Km - Kanamycin
 Lfx – Levofoxacin
 Eto – Ethionamide
 Cs – Cycloserine
 PAS - Para-Aminosalicylate Sodium
 Cfz - Clofazimine
 Lzd – Linezolide
MDR/RIFAMPICIN
RESISTANT TB DRUG
TREATMENT

32. Follow up (MDR, MONO AND POLY
DRTB)
 For MDR TB patients –
 Schedule for sputum culture examination for
MDRTB (no change)
 For mono DR and poly DRTB patients –
 Schedule for sputum culture examination:
 Microbiological: Sputum smear and culture
at second and third months and then culture
examination at three monthly interval till
completion of the treatment.
 For mono/poly DRTB patients –
 IP should given for at least 3 months
 After this, the patient will be reviewed
 If after the 3 months the smear result remains
positive, the sputum sample is sent for genotypic
DST to Rifampicin for CBNAAT or LPA and
liquid/solid culture and DST to see for resistance
amplification
 Shifting from IP to CP will be based on the result of
culture
 The IP can be extended maximum 3 months
 Duration of CP is 6 months

33.  Change from IP to CP will be done after achievement of culture
conversion, that is, two consecutive negative cultures taken at least one
month apart
 In case of delay in culture conversion, IP can be extended from 6 months
to maximum 12 months.
Follow up (MDR TB WITH XDR TB)

34. Outcome for RR/MDR and/or XDR TB
patients (NEW GUIDELINES)
 Cure – Treatment completed as recommended by the National Policy without
evidence of failure and three or more consecutive cultures taken at least 30
days apart are negative after IP
 Treatment completed – Treatment completed as recommended by the
National Policy without evidence of failure but no record that three or more
consecutive cultures taken at least 30 days apart are negative after IP
 Treatment success – The sum of cured and treatment completed
 Treatment failed – Treatment terminated or need for permanent regimen
change of at least two or more ATD in CP because of lack of microbiological
conversion by the end of IP or microbiological reversion in the CP after
conversion to negative or evidence of additional acquired resistance FQ or
second-line injectable drugs, or adverse drug reaction.

35. Outcome for MONO OR POLY DRTB
patients
 Cure – A microbiologically confirmed TB at the beginning of treatment who was culture-negative in the last month
of treatment and on at least one previous occasion
 Treatment completed – A patient who has completed treatment according to the guidelines but does not meet
the definition for cure or treatment failure due to lack of microbiological results
 Failure – Treatment terminated or need for permanent regimen change of at least two or more anti-TB drugs in CP
because of:
 Evidence of additional acquired resistance to Rifampicin, Rluroquinolone or second-line injectable during treatment
 Severe ADR
 Culture-positive during CP or at end of treatment
 Died – A patient who dies for any reason during the course of M/X DRTB treatment
 Loss to follow-up – A patient whose treatment was interrupted for one month or more for any reasons
 Not evaluated – A DRTB patient for whom no treatment outcome is assigned, and this included former ‘transfer
out’.

37. THANK YOU