Update on MDR TB services under RNTCP

1. Update on MDR TB services under RNTCP Dr D Behera Director LRS Institute of Tuberculosis and Respiratory Diseases New Delhi

2. contents • Burden of MDR-TB in India • RNTCP response to the challenge of MDR-TB • Status, vision and challenges • Recent Key policy changes

3. Burden of tb in india • India is highest TB burden country with an annual 1.98 million incident cases • Estimated prevalence of 2.29 million cases • Annual deaths due to TB 2,76,000 • TB/HIV Prevalence • 2.31 million population living with HIV; • ~ 0.9 million co-infected • ~5% of TB patients estimated to be HIV + 21% 24% Source: WHO Geneva; WHO Global Report 2009 & Short update to 2009 report

4. Challenges to TB Control • Wide variations in capacity of Health Systems across the country • Burden due to TB-HIV Co-infection • Ensuring adherence of treatment for migratory population • Large and unregulated Private Sector • Limited availability of new rapid diagnostic tools, drugs and vaccine • Drug Resistance

5. Global Burden of MDR-TB* 0.44 million “incident” cases 27 HBC which account for 85% of all cases 79% • China – 100,000 • India- 99,000 • Russian Fed. – 38,000 • Pakistan- 15,000 • Phillipines-13,000 • South Africa- 13,000 * WHO 2010 M/XDR-TB Global Report on Surveillance and Response

6. Drug resistant TB in India MDR-TB India has 2nd highest MDR-TB burden in the world after China As per DRS surveys done in 2005-06 in the states of Gujarat and Maharashtra prevalence of MDR-TB is: <3% in new cases and 14-17% in previously treated cases As per WHO estimates 99,000 MDR cases emerged in India in 2008 Mono and Poly resistance (Non MDR) TB Relatively high levels of non MDR resistance to H & S seen both in new and previously treated cases, either as mono-resistance or PDR

7. Drug resistance in cases detected in prevalence surveys 1968-2003 H S HR SH Source: TRC Chennai

8. Drug resistant TB in India Extensively Drug Resistant TB (XDR-TB) Reported in India though the data is limited and non-representative Gujarat DRS survey shows No XDR-TB amongst new cases 4% amongst those previously treated cases found to be MDR High levels of non-XDR resistance seen to Ofx and Eto in both new and previously treated cases

9. 57 countries

10. XDR –TB in the world as of March 2010

11. XDR-TB in India

12. Causes of drug resistance • Essentially a man made phenomenon • Inadequate Regimens • Irrational use • Inappropriate combinations • Sub-optimal doses and duration • Inadequate supply or poor quality of drugs • Inadequate drug intake DOTS Strategy adopted by RNTCP addresses all these issues

13. RNTCP Response to Drug resistance TB

14. Multi-faceted approach ….. • Key focus is on prevention • Sustained high-quality DOTS implementation • Promote rational use of anti-TB drugs • Improve laboratory capacity: Diagnosing MDR-TB • Effective treatment of MDR-TB patients • Initiation and rapid scale up of MDR-TB services • Evaluate the extent of the threat of second-line anti-TB drug resistance and management of XDR-TB

15. Strategies….. Prevention of drug resistance through sustained high-quality DOTS implementation Improve laboratory capacity Effective treatment of MDR-TB patients RNTCP DOTS Plus (Category IV services) Promote rational use of anti-TB drugs in the country Implement infection control measures

16. MDR-TB services under rntcp

17. DOTS PLUS – model of care CULTURE AND DST LAB DOTS PLUS SITE (IN-PATIENT FACILITY) SPUTUM SAMPLE RESULT MDR CASE • Follow up protocol • Physical exam • Culture • Kidney function Initial hospitalization followed by ambulatory care DISTRICT MDR CASE • MDR SUSPECT • Cat I/III failure • Cat II sm+ at 4 months of Rx • Contacts of MDR cases HEALTH FACILITY (PHI)

18. Treatment Delivery • Standardized regimen- Cat IV • Intensive phase (6-9 months) • Kanamycin, levofloxacin (ofloxacin), Cycloseine, Ethionamide, Z, E • Continuation phase (18 months) • Levofloxacin (Ofloxacin), Cycloseine, Ethionamide , E • PAS is used as a substitute drug • Three weight bands – • 16-25 Kg ; 26-45 Kg and >45 Kg • Daily DOT (Kanamycin is given 6/7 days) • Follow up • Smear and Culture monthly during IP and quarterly during CP • S Creatinine monthly till Kanamycin is administered • Patients who remain culture + after 6 months of Rx are subjected to SLDST (Km and Ofx) • If found to be XDR will be started on Cat V regimen

19. DOTS Plus Site – Gujarat • DOTS-Plus In-patient site • Tertiary level centre @1 per 10 million population • Dedicated in-patient facility with infection control measures in place • Trained staff available • Facilities for pre-Rx assessment & management of adverse reactions

20. Drug logistics • Quality assured drugs procured nationally • GLC • GoI procurement • Supply line • Loose drugs supplied to State drug stores • Repackaged into 3 monthly IP and CP boxes • Supplied to the districts and downwards • Loose drugs provided at DOTS Plus sites • Logistics and reporting on consumption integrated with first line drugs 3 monthly drug box

21. Recording and reporting • Standardized records and reports • Treatment card • DOTS Plus TB register • C & DST lab register • DTC Referrral register • Quarterly reporting • Case finding report • Interim culture conversion reports • Final outcome report • Plan to establish a dedicated web based DOTS Plus information management system shortly

22. Status of rntcp dots plus services

23. History……. • 2005 • Plan to initiate DOTS Plus services under RNTCP II project (2006-2011) • 24 IRLs to be established and enroll 5000 patients on treatment annually • Constitution of National DOTS Plus committee • 2006 • National DOTS Plus guidelines developed • 2007 • Gujarat and Maharashtra initiate MDR services • 62 patients enrolled on Rx • 2008 • Services available in 8 States- AP, WB, Haryana, Kerala and Delhi • 252 patients enroled on Rx • 2009 • Services available in 10 States-Rajasthan and Orissa • 1415 patients enroled on Rx

24. Present status 10 States implementing MDR services • 10 States implementing DOTS Plus services • 127/632 districts covered • Another 5 States to initiate services shortly • More than 2300 patients on treatment Implementing DOTS Plus Implement shortly Under preparation ~2300 patients on Rx

25. Status of c & dst labs 2Q10 • 14 C & DST labs accredited • 10 IRLs • Gujarat, Maharashtra, AP, Kerala, Delhi, West Bengal, Tamil Nadu, Rajasthan, Orissa and Jharkhand • 4 other sector labs • Medical Colleges- CMC, Vellore; SMS Jaipur • NGO Lab- BPRC, Hyderabad • Private sector – Hinduja Hospital, Mumbai • Labs to be accredited shortly • IRL- Haryana; • KGMU, Lucknow • Labs under accreditation process • IRL-Chattisgarh, Uttarakhand • PGI, Chandigarh; AIIMS, New Delhi, • Quest diagnostics; Ranbaxy Mumbai, Metropolis , Mumbai

26. 10 Govt and 4 other sector labs accredited RNTCP Culture & DST Labs (15 August 2010) NDTC AIIMS LRS Gurgaon JALMA IRL (Accredited) IRL (Under Accreditation) TRC IRL (Equipments being supplied) NTI Med Col / NGO / Private Labs (Accredited) Med Col / NGO / Private Labs (Under Accreditation) Med Col / NGO / Private Labs (Preparatory) National Reference Labs

27. Final Treatment outcomes • First cohort of patients (2007) • Most of them were chronic cases with h/o multiple Cat II treatments • High level of second line drug resistance

28. Dots plus vision….road ahead

29. DOTS Plus Vision…… • By 2010, RNTCP Category IV services will be introduced in all states with complete geographical coverage by 2012 • By 2012, access to laboratory based quality assured MDR-TB diagnosis and treatment for • all smear positive re-treatment TB cases and • new cases who have failed an initial first-line drug treatment • By 2015, access to MDR-TB diagnosis and treatment for all smear positive TB (new and re-treatment) cases registered under RNTCP • RNTCP plans to initiate at least 30,000 MDR cases on treatment annually by 2013

30. Multi-year plan….. *Based on RNTCP 2012 goal of MDR diagnosis for all S+ retreatment patients,

31. Strategies for achieving the vision • Enhancing the laboratory capacity • National Laboratory scale up plan • Additional support from private and NGO laboratories • Scaling up treatment services • Mobilization of Resources

32. Lab scale up plan • ~43 laboratory units to be established • Enhanced sputum processing capacity • Solid culture and DST in all lab units • Line Probe Assay (LPA) in all lab units • Liquid culture in 33 lab units

33. Scaling up treatment services • DOTS Plus sites • 120 DOTS Plus sites across the country (1/10 m population) • Tertiary care centres with in patient facilities • Upgraded to incorporate infection control measures • Function • Pre-treatment evaluation and treatment initiation • Follow up of progress of patient • Management of adverse reactions • Recording and Reporting • Uninterrupted supply of adequate quality assured second line drugs • Provision for daily DOT • Includes 6-9 months of injectables

34. Resource mobilization • Lab scale up to be undertaken with support from • UNITAID Expand TB • Global Fund –RCC and Rd 9 • World Bank • USAID through WHO • Second line drugs

35. Recent Key policy changes

36. Recent Key policy changes…. • Revision of MDR-TB suspect definition • Cat I and III failures • Cat II patients who remain smear positive after 4 months of treatment or later • Contacts of MDR-TB cases found to have smear positive TB • Replacement of Ofloxacin by Levofloxacin in Cat IV regimen • Regimen will now be • IP: Km, Lvx, Cs, Eto, Z, E (6-9 months) • CP: , Lvx, Cs, Eto, E (18 months) • Earlier exclusion criteria (pregnancy, paediatric age group, intake of SLD >1 mth) removed

37. Key policy changes ….2 • Guidelines on the management of XDR-TB patients under RNTCP finalized • XDR-TB to be suspected in Category IV patients who remain culture positive after 6 months of treatment, SLDST to be done • Such patients are to be treated with the Category IV regimen • Guidelines on management of patients who default from Category IV treatment for more than 2 months and subsequently report back to RNTCP developed • Management of DR-TB patients other than MDR-TB • Patients with any rifampicin resistance will be treated with the MDR TB regimen, in addition to those with MDR-TB. • Need to generate more evidence on treatment of other forms of mono and poly (non MDR) drug resistant TB

38. Challenges in achieving the vision

39. Challenges in diagnosis of MDR TB… • Delay in establishment of accredited state level laboratories due to a host of reasons • Sub-optimal functioning of the accredited labs • Non-availability of trained manpower • Dedicated regular staff in addition to the contractual posts • Uninterrupted power supply • Diagnostic delay with conventional method (3-4 months turn around time) • Special requirements for introduction of newer rapid diagnostics- laboratory infrastructure and training

40. Treatment Challenges……. • Long duration, toxic, expensive treatment • ~2,100 $ per patient course • Daily ambulatory DOT • 6-9 months of injectables • Availability of DOTS-Plus in-patient sites (1 per 10 million population) • Extensive training, supervision and monitoring needed at all levels • Ensuring treatment adherence and timely follow up • Uninterrupted supply of second line drugs

41. Rational use of anti-TB drugs • Problem • In 2006, substantial quantity of FLDs and almost 100% of SLDs were sold and used outside of RNTCP • Well documented that management of TB patients outside of RNTCP is often poor leading to risk of failure of treatment and development of drug resistance • Large unregulated private sector • Conflict of Interest • Easy availability of anti TB drugs • Steps to promote rational use of anti TB drugs • “Chennai Consensus Statement” developed and disseminated • IMA on behalf of RNTCP interacting with MCI for guidelines to all healthcare providers on rational use of anti TB drugs • Interactions with office of DCGI to draft guidelines for the regulation of anti-TB drugs, especially SLDs, • Encouragement of additional pre-qualified drug manufacturers

42. Infection Control……. • Problem • Infection control considered synonymous with waste management • Lack of National guidelines on Airborne Infection control in context of TB • Overcrowding/lack of space at health facilities • Lack of awareness and commitment of hospital administrators • Steps taken • National Airborne Infection Control Committee constituted • “National guidelines for airborne infection control” for all healthcare facilities developed and pilot tested • Provision of support to upgrade IC measures at • DOTS-Plus site indoor facilities • Intermediate Reference laboratories • Collaboration with AIDS control programme to ensure IC measures at ICTCs and ART centres • Encouraging Medical Colleges (through NTF, ZTF and STF mechanism) to develop and implement infection control measures

43. Role of medical colleges in supporting scale up of dots plus services under rntcp

44. strengthening lab capacity • Medical colleges (public and private) with functional Mycobacteriology laboratories encouraged to apply for accreditation • Steps for accreditation- • Download the application format for accreditation from www.tbcindia.org • Submit the format to the State TB Officer with a copy to CTD • Pre-accreditation visit • Proficiency testing • Accreditation • Once accredited the lab can provide diagnostic and follow up services under RNTCP • RNTCP will provide financial/commodity assistance for services provided

45. Treatment services • RNTCP can benefit from the rich experience of the Medical Colleges in treating MDR TB • Medical Colleges (Public and Private) can serve as DOTS Plus sites • Dedicated in patient facility (ward) • Separate space/ward for Male and Female patients • Adequate number of beds • Facilities for pre-treatment evaluation • Constitution of DOTS Plus site Committee • Upgradation to incorporte infection control measures • Responsibilities • Treatment initiation and follow up of MDR patients • Management of adverse reactions • Recording and Reporting • RNTCP support • Funds upto 10 lakhs for upgradation • Human Resource- 1 Medical Officer; 1 Statistical Assistant • Computer with Internet facility

46. Thought for the day