Burden of TB Dr. Manoj Verma I/C IRL Department Bhopal District Tuberculosis Officer Bhopal Suptd. TB Hospital, Idgah Hills, Bhopal
ROBERT KOCH ELECTRON MICROGRAPH ACID FAST OF MTB STAINIG OF MTB
TRANSMISSION OF TB PREVENTION OF TUBERCULOSIS
“Safe in - patient” Practices – Masks to patients, cough hygiene
DOTS Plus DOTS
OUT COME • CURE 85% • CURE 34 % • SUCCESS 90-95% • SUCCESS 49 % • DEFAULT 5% • DEFAULT 26 % • DEATH 3% • DEATH 22 % • FAILURE 3-5% • FAILURE 18 %
Newer anti TB drugs • Bedaquiline (BDQ) – New class of drug, diarylquinoline – Targets mycobacterial ATP synthase, – Strong bactericidal – Extensive tissue distribution up to 5.5 months post stopping BDQ. – Significant benefits in improving the time to culture conversion in MDR-TB patients . – Active drug safety monitoring (aDSM) – Cross-resistance with Clofazimine. • Delamanid
Newer anti-TB drugs • Bedaquiline The new drug with anti-TB effect, was approved for treatment of multidrug resistant TB by US FDA in late 2012 • Strong bactericidal and sterilizing activities against M.tb • The drug has an extended half-life up to 5.5 months post stopping BDQ due to high volume of distribution, with extensive tissue distribution, highly bound to plasma proteins • shown significant benefits in improving the time to culture conversion in MDR-TB patients • Indication: pulmonary adult MDR-TB patients – when an effective treatment regimen containing at least four second- line drugs in addition to Z cannot be designed or – when there is documented evidence of resistance to any FQ and/or SLI in addition to MDR TB
Newer anti-TB drugs • BDQ was followed by the approval of another new drug Delamanid (Dlm) by the stringent regulatory authority of various countries • introduction of Dlm under RNTCP is ongoing and guidance for the same will be released subsequently as an addendum to these guidelines
Integrated Drug Resistant TB Algorithm Presumptive TB All diagnosed TB patients Key/Vulnerable populations • Non responders to • Paediatric age group treatment • People living with HIV CBNAAT • DR-TB contacts • EPTB sites • Previously treated TB • Smear negative/NA with X- • TB-HIV co-infection ray suggestive of TB • New TB cases $ For discordance on LPA for RR-TB RS TB RR TB – repeat CBNAAT at LPA lab First line Shorter MDR TB treatment Regimen (9-11 m)# FL-LPA* SL - LPA** FQ and SLI Sensitive FQ and/or SLI Resistance H Resistant H Sensitive H mono/poly Continue same regimen Newer Drugs & DST Continue First line resistant TB (shorter MDR or H guided treatment treatment regimen mono/poly regimen) In case of addl resistance, failing regimen, drug intolerance, return after interruption (>1 m) or emergence of any exclusion criteria # Conventional MDR TB Regimen (24 m) for pregnant women or for EP TB patients those who are not eligible for shorter regimen. * Offer molecular testing and treatment for H mono/poly resistance to TB patients prioritized by risk as per the available lab capacity **LC DST (Mfx 2.0, Km, Cm, Lzd) will be done only for patients with any resistance on baseline SL-LPA. DST to Z, Cfz, Bdq & Dlm would be considered for policy in future, whenever available, standardized & WHO endorsed. $ States to advance in phased manner as per PMDT Scale up plan for universal DST based on lab capacity and policy on use of diagnostics
Integrated Drug Resistant TB Algorithm Integrated Drug Resistant TB Algorithm Presumptive TB All diagnosed TB patients Key/Vulnerable populations • Non responders to • Paediatric age group treatment CBNAAT • People living with HIV • DR-TB contacts • EPTB sites • Previously treated TB • Smear negative/NA with X- • TB-HIV co-infection ray suggestive of TB • New TB cases $ For discordance on LPA for RR-TB RR TB RS TB – repeat CBNAAT at LPA lab First line Shorter MDR TB treatment Regimen (9-11 m)# FL-LPA* SL - LPA** FQ and SLI Sensitive FQ and/or SLI Resistance H Resistant H Sensitive H mono/poly Continue same regimen Newer Drugs & DST Continue First line resistant TB (shorter MDR or H guided treatment treatment regimen mono/poly regimen) In case of addl resistance, failing regimen, drug intolerance, return after interruption (>1 m) or emergence of any exclusion criteria # Conventional MDR TB Regimen (24 m) for pregnant women or for EP TB patients those who are not eligible for shorter regimen. * Offer molecular testing and treatment for H mono/poly resistance to TB patients prioritized by risk as per the available lab capacity **LC DST (Mfx 2.0, Km, Cm, Lzd) will be done only for patients with any resistance on baseline SL-LPA. DST to Z, Cfz, Bdq & Dlm would be considered for policy in future, whenever available, standardized & WHO endorsed. $ States to advance in phased manner as per PMDT Scale up plan for universal DST based on lab capacity and policy on use of diagnostics
MDR/RR-TB with additional resistance to any/all FQ or SLI • All patients with additional resistance to FQ class AND/OR SLI class on SL-LPA would be assessed for eligibility for newer drug containing regimen. • Patients who have consented and are found to be eligible would be initiated on newer drugs containing the regimen while rest of the patients would be initiated on a DST guided regimen and reclassified.
Inclusion criteria The criterion for patients to receive BDQ as approved by the Apex Committee is: • Adults aged > 18 years having pulmonary MDR-TB. Additional requirements • Non pregnant females or females not on effective hormonal birth control methods are eligible • Willing to continue practicing birth control methods throughout the treatment period or • have been post-menopausal for the past 2 years. • Patients with controlled stable arrhythmia can be considered after obtaining cardiac consultation.
Exclusion criteria Currently having uncontrolled cardiac arrhythmia that requires medication Has any of the following QT/QTc interval characteristics at screening: – A marked prolongation of QT/QTc interval , e.g. repeated demonstration of QTcF (Fredericia correction) interval > 450 ms; – A history of additional risk factors for Torsade de Pointes , e.g. heart failure, hypokalaemia, family history of long QT syndrome ; – has evidence of chorioretinitis, optic neuritis, or uveitis at screening which precludes long term linezolid (Lzd) therapy;
Eligibility for Bedaquiline Bdq is indicated in adult MDR-TB patients not eligible for the newly WHO-recommended shorter regimen. These may include: • MDR/RR-TB patients with resistance to any/all FQ OR to any/all SLI • XDR-TB patients • Mixed pattern resistant TB patients • Treatment failures of MDR-TB + FQ/SLI resistance OR XDR-TB • MDR/RR-TB patients with extensive pulmonary lesions, advanced disease and others deemed at higher baseline risk for poor outcomes
Bedaquiline: Dosage • Week 0 – 2: BDQ 400 mg (4 tablets of 100 mg) daily (7 days per week) + OBR • Week 3 – 24: BDQ 200 mg (2 tablets of 100 mg) 3 times per week (with at least 48 hours between doses) for a total dose of 600 mg per week + OBR • Week 25 (start of month 7) to end of treatment: Continue other second-line anti-TB drugs only as per RNTCP recommendations The dosage of BDQ would apply to all weight bands while the dosage of other drugs in the OBR would be as per the weight bands in accordance to the RNTCP PMDT guidelines.
Bedaquiline: Administration
Management of patients found to be ineligible or who did not consent for BDQ “Patients who could not be initiated on a BDQ containing regimen (either found ineligible or who did not consent for BDQ) would be treated with treatment regimen tailored as per the DST guided treatment”
DST guided regimen with or without newer drugs for initiating treatment of MDR/RR-TB patients with additional resistance to FQ class and/or SLI class, at nodal DR-TB centre based on SL-LPA Resistance DST Guided Intensive Phase Continuation Principle of Pattern Regimen class Phase regimen design Regimen with New drugs for MDR-TB + FQ / SLI resistance 0 GpA + 1GpB + 2 (6-9) Km Eto Cs Z (18) Eto Cs MDR/RR + resistance GpC + Z + add on Lzd 3 Cfz + (6) Bdq Lzd 3 Cfz to FQ class MDR/RR + 2 GpC + 1 GpD2 1 GpA + 1 GpB 1 + resistance to FQ (6-9) Lfx Cm 1 Eto class / SLI 1 class (18) Lfx Eto MDR/RR+ resistance 2 GpC + Z + add Cs Z Lzd 3 Cfz + to SLI 1 class Cs Lzd 3 on 2 GpC + 1 (6) Bdq GpD2 Regimen MDR-TB + FQ / SLI resistance: (without new drugs) 1 GpA 2 + 1GpB + 2 (6-9) Mfx h2 Km Eto (18) Mfx h2 Eto MDR/RR + resistance GpC + Z + add on MDR/RR + Cs Z Lzd 3 Cfz Cs Lzd 3 Cfz to FQ class 2 GpC resistance to FQ 1 GpA + 1 GpB 1 + 6-9) Lfx Cm 1 Eto class / SLI 1 class MDR/RR+ resistance (18) Lfx Eto 2 GpC + Z + add to SLI 1 class Cs Z Lzd 3 Cfz Cs Lzd 3 on 2 GpC 1 If only Km resistant (at eis mutation), then add Cm in IP upfront in the regimen design. 2. In patients with MDR/RR + FQ Class resistance, XDR-TB and Mixed pattern resistance where a new drug is not considered in the regimen for any reason, Mfx h would be added upfront in the regimen design and the decision to continue or replace it would be taken based on LC-DST results to Mfx (2.0) by NDR-TBC 3. Lzd to be replaced with a suitable drug if found to be resistant on LC-DST. In such situation the patient must be reclassified as mixed pattern DR-TB
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