Tuberculosis in Indonesia: Tipping the balance towards better control

1. Tuberculosis in Indonesia: Tipping the balance towards better control Bachti Alisjahbana Medical Faculty, Padjadjaran University, TB Operational Research Group, National TB Program, Indonesia

2. Overview TB Situation Program challenges Operational research Biomedical research Conclusion

3. Indonesia Pop = 247 million

4. 22 High Burden Countries, 2012 China 14.3% Indonesia 5.8% South Africa 4.9% India 21.1% Nigeria 4.9% Bangladesh 3.8% Ethiopia 3.3% Pakistan 3.2% Other 15.9% Philippines 2.7% • In Indonesia : • Prevalence: 730.000 (297/100 thousand) • Incidence: 460.000 (185/100 thousand) • Mortality: 67.000 • HIV in TB = ~3% WHO report 2013

5. Target CDRI ndo 75%, Global 70% Target SR Indo 86%, Global ≥ 85% s/d 3rd Quarter (data gathered by 10 Jan 2012)

6. National TB Program Achievement (WHO, 2013)

7. Number of TB cases in Bandung municipalyear 2012 (population of ~ 2,4 million) PHC: Public Health Center; P:pulmonary; EP:Extra pulmonary; AFB: Acid Fast Bacilli

8. Overview TB situation Program challenges Operational research Biomedical research Conclusion

10. TB Laboratories 3 national Surabaya Bandung Univ Indo, Jakarta 2 referral lab. just passed QA. 5.566 TB lab. 59% (3.284) EQAS, 75% good result

11. TB-MDR Among new patients, resistance to any drug 17.1% MDR-TB 1.8%. Retreatment cases, Resistance 34.3% and MDT 17.1%. WHO estimated 6900 cases are MDR TB (annual incidence). Total notification MDR-TB was 428, (0.12% coverage).

12. TB-HIV HIV prevalence in new TB is 3.3%. ~ 1% TB patients know their HIV status. Among HIV positive, only 29% enrolled on ART.

13. National Strategy 2016Toward a free-TB, healthy, just and self- reliant society Technical Strategies Scaling-up and improve quality DOTS Addressing TB/HIV, MDR-TB, & the needs of poor and vulnerable Engaging all public and private providers in implementation of ISTC. Empowering TB patients & communities

14. National Strategy 2010-2016 Functional Strategies Strengthening health system, HRD and TB control program management Increasing commitment of central and local government Enhancing research, development and utilization of strategic information

15. Overview TB Situation Program challenges Operational research Biomedical research Conclusion

16. TB Operational Research Group (TORG) Under the NTP Facilitate operational research (OR) Increase capacity to conduct OR through intensive courses Review TB research proposals submitted to NTP Provide technical assistance in OR at National level. Facilitate implementation of OR results in program

17. Operational Research Topics

18. Scope of the TORG Network

19. Evaluation of implementation of Xpert-Mtb-Rif National level OR 5 Xpert deployed in 2012, 10 more in 2013 Aiming for HIV and MDR-TB Increase D/ yield, faster detection MDR TB Hesitation rely only xpert Culture still needed

20. TB prevalence survey

21. TB prevalence surveyPreliminary findings Smear-positive TB prevalence higher than previously estimated* Probably more sensitive screening, & diagnosis Prevalence in rural > urban Prevalence peaked in 25-34 age. Ongoing significant transmission? Gaps between prevalence and notifications are greater in men and oldest age

22. Overview TB Situation Program challenges Operational research Biomedical research Conclusion

23. Biomedical research • New findings • → new challenges

24. First project (2000-2005) • Immunogenetic basis of susceptibility to and disease manifestations from tuberculosis • Why patient gets TB • What immunogenetic pattern? • Others condition? • 900 Cases, 1000 Control • Funded by KNAW

25. Setting

26. Double Trouble... TB & DM No DM DM Body mass index (kg/m2) Body mass index (kg/m2) 40 40 35 35 30 30 25 25 20 20 15 15 10 10 10 20 30 40 50 60 70 10 20 30 40 50 60 70 age (years) age (years) Tuberculosis patients Control subjects Alisjahbana et al, Int Journ of Tub and Lung Dise, 2006, 10(6), 696-700

27. Europe DM: 24 million (14%) TB: 0.2 million (2%) North America DM: 23 million (13%) TB: 0.1 million (1%) Asia DM: 102 million (60%) TB: 5.6 million (62%) Africa DM: 11 million (6%) TB: 2.9 million (32%) South America DM: 10 million (6%) TB: 0.3 million (3%) Oceania DM: 1 million (1%) TB: 0.02 million (0.2%) Double trouble of TB & DM in Asia

28. EC, Fp7 To determine prevalence of DM among TB patients & vice versa feasible, accurate and cost-effective ways of screening. DM management level required with TB treatment glucose control effect on TB treatment outcome Pathopysiological studies

29. Pharmacokinetic studies Rifampicin plasma concentration is significanty reduced in TB-DM patient Nijland et al, 2006, CID

30. TB Diagnostic (Lidya Chaidir et al, 2013)

31. Bacterological studiesDrug Sensitivity Testing? Figure 3. AMK = Amikacin, INH = Isoniazid, RIF=Rifampicin, PAS=Para aminosalisilic acid, ETB=Ethambutol, STR=Streptomicin. Numbers shows antibiotic concentration in medium (mg/l). Multiwell method The proportional method

32. TB Beijing genotype • Related with higher disease severity? • Our studies • More severe • More treatment failure R. Van Crevel, EID, 880 Vol. 7, No. 5, September-October 2001

33. Population Structure of M. tuberculosis in Papua vs Java Mtb Finger Printing, show huge variability across Indonesian Islands MIRU-VNTR and MLPA later shows more distinctive power (Lidya Chaidir et al, 2013)

34. Latent TB IGRA vs Mantoux in children case contact

35. Latent TB Treatment • Multicenter clinical trial (2012-now) • latent TB (TST +) • 800 adult, 300 child • 4Rif vs 9INH • safety & efficacy • immunological pattern

36. Conclusion • Host • Diabetes • Immuno-genetic • HIV-TB Diagnosis & Management Problems Coevolution study • Operational • Research • Diagnostic • Imuno-diagnostic • Clin evaluation • Pharmaco kinetics • Bacteriology • Beijing study • Drug susceptibility test • Transmission dynamic • MDR-TB

37. Thank You TB research Group Bandung TB Operational Research Group

38. 5 Level of TB Laboratory Satellite facility Health facility lab. TB microscopy. Intermediate TB laboratory located in District. Cross check service level I Province referral TB laboratory providing cross check for level 2 National referral TB laboratory.