Programmatic management of drug resistant tuberculosis(pmdt)

Programmatic Management of Drug Resistant TB - India
as per 2011 Guidelines.
Key Concepts

1. Programmatic Management of Drug Resistant Tuberculosis(PMDT) Dr. Anisha Mohan. P Dr. Murali . R Dr. Uppilli Venkata Raghavan Department of Community Medicine, CHRI

2. Overview Introduction Problem statement Programme components Vision of PMDT Organisational structure Laboratory services Management of MDR TB Recording and reporting system Recent advances

3. Introduction- PMDT Programmatic Management of Drug Resistant TB i.e DOTS PLUS in 2007 in 2 states Program based MDR TB diagnosis, management and treatment Integrated under RNTCP Supplementary services under the expanded framework of DOTS Modest progress made from 07-09

4. Vision of PMDT : By end 2012 , complete nationwide geographical coverage of access to basic MDR TB diagnostic and treatment services; By 2012-13, expanded access to 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 , nationwide access to MDR-TB diagnosis and treatment for all smear positive TB (re-treatment or new*) cases registered under RNTCP before or early during their treatment* RNTCP expects to treat about 1,60,000 MDR-TB and 4,100 XDR-TB cases over the next 5 years (2012-2017).

5. Why do we have to target MDR TB? Poor control of TB --- higher drug resistance Good treatment --- preventing emergence of resistance MDR Tb cost

6. Drug resistance in TB Two types Acquired drug resistance : Due to inadequate, incomplete or poor treatment quality Primary drug resistance : Person has been infected with a drug resistant Tb strain

7. Factors contributing to drug resistance : Inappropriate treatment Inadequate supply/quality Inadequate drug intake / treatment response Inappropriate guidelines Poor quality medicines Lack of information Non-compliance with guidelines Unavailability of certain medicines Lack of means to adhere to treatment (transportation, food, etc.) Absence of guidelines; Poorly organized or funded TB control programmes Poor storage conditions Adverse effects Poor training Wrong dose or combination Social barriers Financial disincentives Poor regulation of Medicines HIV Poor patient education Diabetes mellitus No monitoring of treatment Undernutrition, Malabsorption Poor management of ADR Substance abuse/dependency, Psychiatric condition

8. Problem statement : Globally 5% of estimated total TB cases 3.5% of new TB cases 20.5% of previously treated cases in some countries 480,000 estimated (2013) More than half India, China, Federation of Russia *http ://www.who.int/tb/publications/global_report/gtbr14_supplement_web_v3.pdf

9. Estimated number of MDR TB cases among notified cases

10. Status of MDR TB RESPONSE 300,000 MDR TB CASES ESTIMATED among reported cases Actual number of cases DETECTED and reported under NTP Actual number of cases started on treatment Percentage of cases declared successful outcome

11. Problem statement : India MDR TB : 1- 3% new cases, 12% re treatment cases* Newer figures : 3% ; 12-17%** WHO estimate : 2009 : 99,000 cases emerged out of which 64,000 notified *NIRT and NTI ** DRS in Gujarat, Maharashtra, Andhra Pradesh

12. Core components of PMDT

13. Organisational Structure

14. Co- ordination at different levels Supported by National PMDT Committee NTI, NIRT, LRS, Medical colleges, UMoHFW , WHO Tailored to fit the local needs Provision of DOTS, Food housing, vocational support, reduce stigma

15. Strategies for prevention of MDR TB National TB scale up plan 2011-2012

16. Organisation of laboratory network : Obtain certification from NRL Transportation of specimens Maintain registers Overall quality check Training of Staff Performs DST for 1 st , 2 nd line drugs EQA of IRL Prompt referral Sputum microscopy Maintain registers Perform DST for 1 st line Receive samples from NRL Co ordinate with DTO

17. Minimum requirements for ( IRL) or any other RNTCP-certified Culture & DST laboratory- diagnostic culture on solid and/or liquid media, confirmation of resistance to rifampicin(LPA or other) confirmation of the species as M. tuberculosis or (NTM ); testing for susceptibility to at least INH & R by culture . c linical laboratory services Laboratory services :

18. Definitions MDR TB suspect : A patient suspected of drug-resistant tuberculosis, based on RNTCP criteria for submission of specimens for drug-susceptibility testing. MDR-TB case : A TB patient whose sputum is culture positive for Mycobacterium tuberculosis and is resistant in-vitro to isoniazid and rifampicin with or without other anti-tubercular drugs based on DST results from an RNTCP- certified Culture & DST Laboratory

19. MDR Suspect Criteria Criteria A – All failures of new TB cases Smear + ve previously treated cases who remain smear + ve at 4th month onwards All pulmonary TB cases who are contacts of known MDR TB case Criteria B – in addition to Criteria A: All smear + ve previously treated pulmonary TB cases at diagnosis Any smear + ve follow up result in new or previously treated cases Criteria C – in addition to Criteria B All smear - ve previously treated pulmonary TB cases at diagnosis, HIV TB co-infected cases at diagnosis

20. XDR TB case: An MDR TB case whose recovered M. tuberculosis isolate is resistant to at least isoniazid, rifampicin, a f luoroquinolone ( ofloxacin , levofloxacin, or moxifloxacin) and a second-line injectable antiTB drug (kanamycin, amikacin, or capreomycin ) at a RNTCP-certified Culture & DST Laboratory

21. Diagnostic method Lowenstein – Jenson medium, MGIT Line probe assay Xpert MTB/Rif METHOD TIME TAKEN LJ MEDIA 84 DAYS MGIT 42 DAYS LPA 72 HOURS CB-NAAT 2 HOURS

22. CB- NAAAT – Cartridge based Nucleic Acid Amplification Testing Xpert MTB/R assay Highly automated Minimal training Free from cross contamination Internally quality assured Within 2 hours (90min)

23. Choice of diagnostic method Rapid , Highly accurate R Resistance

24. Specimen collection General guideline - collection of sputa is one spot and one morning, Exception : long distance R ecently discharged material from the bronchial tree M inimum amounts of oral or nasopharyngeal material. V olume of 3-5ml. C ollect in a sterile container Transported as soon as possible after collection. R efrigerated up to 1 week Transported in cold chain within 72 hours

25. Transport

26. Quality assurance for DST and culture Retesting exercise – new lab Regular panel testing - by NRL Certification requirements - >90% sensitivity required Period of 2 years “IRL Mycobacteriology Certification Pre-Assessment Tool” (RNTCP IRL APAT) by CTD .

27. Panel testing

28. Operational procedure to identify and refer for C-DST under Category B

29. Opportunities to detect MDR TB suspect At referral Referring provider should indicate need for DST, and what makes that patient eligible (e.g. prior treatment, MDR suspect) At time of specimen submission LT should assess history prior anti TB treatment, results At time of sputum results LT and MO routinely assess if DST required At categorization MO should consider if DST required At recording, registration or follow up STS/STLS should check for DST results for all registered smear positive re treatment patients And for follow up results of all smear positive patients During routine supervision STS/STLS review smear positive results for DST submission

30. Communication between C-DST and providers

31. Overview

32. Management of patients while waiting for results If the LPA results are available within 7 days of sample collection directly placed on the appropriate DST-driven regimen, i.e. - For RIF-sensitive patients, place on the Regimen for previously treated cases - For RIF-resistant patients, referral for pre-treatment evaluation - MDR TB. If results may be delayed more than 7 days of sample collection , the patient should be initiated on RNTCP DOTS treatment till the results are available.

33. Management approaches Admitted at DR TB Centre Not admitted at DR TB Centre - Pre-treatment evaluation - DR-TB Centre -Pre-treatment evaluation conducted locally and the patient/ results sent to the DR-TB Centre committee - DR-TB Centre committee decides to initiate MDR TB treatment. - DTO informed through eMail - DTO initiates Regimen for MDR TB with concurrence of DR-TB Centre committee - Treatment card opened - Patient r egistered in the RNTCP PMDT Register at DR-TB Centre. - Patient discharged after at least one week post treatment initiation with maximum 7 days drug supply for the transit . - Treatment card opened by DTO and registered in District RNTCP PMDT Register. - First dose given under supervision at the DTC. - Copy sent to DR-TB Centr e for recording in RNTCP PMDT Register at the DR-TB Centre. - The PMDT TB number of will be provided by the concerned DR TB Centre.

34. Regimen for MDR - TB 6 (9) Km Lvx Eto Cs Z E / 18 Lvx Eto Cs E [Reserve/Substitute drugs : PAS, Mfx , Cm]

35. Regimen for XDR TB 6-12 Cm, PAS, Mfx , High dose-H, Cfz , Lzd , Amx / Clv / 18 PAS, Mfx , High dose-H, Cfz , Lzd , Amx / Clv [Reserve/Substitute drugs: Clarithromycin, Thiacetazone ]

36. Algorithm for treatment of M/XDR patients who default and return within 6 months

37. Algorithm for treatment of M/XDR patients who default and return after 6 months

38. Treatment and outcome definitions Cure : A patient who has completed treatment and has been consistently culture negative( with at least 5 consecutive negative results in the last 12 to 15 months ). If one follow-up positive 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

39. Treatment failure: Treatment will be considered to have failed if two or more of the five cultures recorded in the final 12-15 months are positive, or if any of the final three cultures are positive. Death : A patient who dies for any reason during the course of M/XDR-TB treatment Treatment default: A patient whose treatment was interrupted for two or more consecutive months for any reasons.

40. Transfer out: A patient who has been treated (DR-TB Centre in this case) and for whom the treatment outcome is not known . Not required within district. Treatment stopped due to adverse drug reactions: A patient who develops severe adverse reactions and could not continue the M/XDR-TB treatment in spite of the management of the adverse reactions as per the defined protocols and decision has been taken by the DR-TB Centre committee to stop treatment 

41. Treatment stopped due to other reasons: A patient who could not continue the M/XDR-TB treatment for any other medical reason (than adverse drug reactions), and a decision has been taken by the DR-TB Centre committee to stop treatment.

42. Switched to Regimen for XDR TB: A MDR-TB patient who is found to have XDR-TB by an RNTCP certified C-DST laboratory, who subsequently switched to a regimen for XDR TB treatment initiated. Still on treatment: An M/XDR-TB patient who, for any reason, is still receiving their treatment at the time of the submission of the Treatment Outcome Report.

43. Treatment adherence Directly observed therapy Social support Socio economic interventions Effective management of adverse drug reactions

44. MDR TB in special situations MDR TB in pregnancy HIV co infection Surgical management Paediatric With renal impairment

45. Contacts of MDR TB If the contact is found to be suffering from pulmonary TB disease irrespective of the Smear results, he/she will be identified as an “MDR-TB suspect”. Early diagnosis and appropriate treatment of MDR-TB cases Screening of contacts Further research into effective and non-toxic chemoprophylaxis

46. Logistics of second line drugs Centralised procurement system Supplied directly to State Drug Store Receipt intimated to CTD Lose drugs packed into types :- Type A (Core oral drug box) Type B (IP Plus) Type C (Na PAS)

47. Distribution of second line drugs

48. Recording and reporting system Aims of the information system Managers at different levels are aware - Aid staff in treatment units to provide treatment R eports, forms Both electronic, hard copies Quaterly , six monthly and annual reports Training of staff for data entry

49. Recent advances : Newer drugs Bedaquilline Delamanid

50. References Guidelines for PMDT in INDIA May 2012 WHO publication on DR TB Report 2013 Drug resistance tuberculosis ; Drug Resistance and Surveillance. Supplement Global Tuberculosis Report 2014 - WHO

51. Topics for follow up Management of Extra Pulmonary TB Drug Dosages Side effects of drugs MDR TB in special situations

52. Thank you