1 I ntroduction of New Laboratory Diagnostics especially liquid culture, line probe assay and Xpert MTB/RIF diagnostic Test in Indonesia BY DYAH ERTI MUSTIKAWATI, NTP Manager, MOH-Indonesia REGIONAL WORKSHOP ON TB CONTROL PLANNING, IMPLEMENTATION AND MONITORING Jakarta, Indonesia, May 2012

Background 2  Earlier and improve TB case detection to reduce the diagnostic delays are global and national priorities for TB control  Alarming increases in MDR-TB  TBMDR pilot implemetentation and KAP survey of Private Practitioners in 12 provinces  Low reported of HIV-associated TB largely goes undetected due to the limitations of current diagnostic techniques  WHO endorsed Xpert MTB/RIF in December 2010 and recommended to implement it in specific settings  Xpert MTB/RIF expect to improve TB diagnosis in HIV patient and expand capacity as proxy to diagnose MDR-TB.

6 Pilars Indonesia Public Private Mix (INA-PPM) Comprehensive Model Toward Universal Access to Qualified TB care Community System Strengthening -Function as advocator  raise fund and commitment, - Increase public awareness, function as public watch to ensure deliveries of quality services, -increasing awareness of right and responsibility of the patients (patient's charter). -Social Mobilization, suspect identification, increasing demand creation, intensifying the services of TB in slum areas and prison -Leading: NGO, FBO, CSO -TA: FHI, other partners Qualified TB Diagnostic -Approach: Strengthening lab network and Quality Assurance (public and private)  DST, Culture and Microscopic -Leading: Directorate of Medical Support - TA: KNCV and JATA Pelayanan Rumah Sakit Publik/Swasta - Approach : Hospital Accreditation, Implementation TB DOTS as Minimum Standard requirement for accreditation of Hospitals - Leading: Directorates of Referral Health Services -TA: KNCV Quality DOTS services by Private Practitioners and Specialist Quality of anti TB Drug Dispensing and rational Use of Drug - Approach: Implementation of ISTC for all TB care and treatment from all care providers, increasing professional responsibility to cure TB patients, rewarding through cumulative credits mechanism for licensing/certification -Leading: IMA -TA: ATS, -Approach: law enforcement, establishment of networking and monitoring system, WHO prequalification -Leading: Indonesian Pharmacist Association, DG of Pharmaceutical Services, Indonesian FDA -TA: USP and MSH Basic DOTS Services At Puskesmas -Approach: Surveillance System Strengthening and MIFA, Improving quality of care, increasing coverage of TBHIV, reaching un-reach pop at remote are (DTPK), increasing referral to Quality DOTS Services -Leading: NTP -TA: WHO, FHI and other partners

Current Lab Network/Services 4  Microscopic Labs  at all PHCs, Clinics and hospitals (around 10,000 centers)  National EQA System is still under construction  5 labs have reach international performance and certified for 1 st and 2 nd line DST. 1.BBLK Surabaya, East java 2.Microbiology UI, Jakarta 3.RS Persahabatan, Jakarta 4.BLK Bandung, West Java 5.NEHCRI Makassar, South Sulawesi  3 of those labs are National TB Reference Lab (NRL). 1.BBLK Surabaya (NRL for culture/DST) 2.Microbiology UI (NRL for research and biomoleculer) 3.BLK Bandung (NRL for microscopic)

Certified Culture/DST Laboratories Microbiology - UI DKI Jakarta BLK BandungPersahabatan Hosp. West Java East JavaSouth Sulawesi BBLK Surabaya NEHCRI Makassar

National TB Reference Laboratories Microbiology - UI NRL for research & Biomoleculer BLK Bandung NRL for Microscopic NRL for Culture/DST BBLK Surabaya

Microbiology - UI BBLK Surabaya NEHCRI Makassar BLK Bandung Persahabatan Hosp. Adam Malik Hosp. BBLK Palembang BLK Jayapura BLK Banjarmasin UGM-DIY BLK Semarang Sanglah Hosp BLK-Lampung Rotinsulu Hosp. BLK Samarinda BBKPM Solo BBLK Makassar Note : Certified : 5 labs Renovated: BSL 2 plus: 5 labs Next expansion of C/DST labs: 7 labs Expansion Plan of Culture/DST Lab until 2014

Key areas of progress since 2009 No Key Areas National TB Lab action Plan-Available 2National TB Reference Lab-3 labs 3Certified FL DST Lab3 labs5 labs 4Certified SL DST Lab-5 labs 5Improve Biosafety (Renovation of Culture/DST Lab to meet BSL 2 plus standard) -4 labs completed 2 labs in progress 6Implementation of LPA-3 labs 7Implementation of GeneXpert-5 labs (up to March)

National TB Lab Action Plan,

Cost Sharing in Establishing BSL 2 plus Lab for Culture/DST 10 Lab/ Institution DesignRenovationEquipmentsTrainingTechnical Assistance Microbiology UGM TBCAP TBCARE I BLK SemarangTBCAPAPBD, TBCAP APBN, TBCAP, GF-ATM TBCAPTBCAP TBCARE I BLK JayapuraTBCAP APBN, TBCAP, GF-ATM TBCAP, GF-ATM TBCAP TBCARE I Adam Malik Hospital TBCAPGF-ATM TBCAP, GF-ATM TBCAP TBCARE I BLK Banjarmasin GF-ATM APBN GF-ATM TBCAP, GF-ATM TBCAP TBCARE I

Renovation of TB Culture/DST Lab: Microbiology UGM 11

12 Renovation of TB Culture/DST Lab: BLK Jayapura, Papua

13 Renovation of TB Culture/DST Lab: BLK Semarang, Central Java

Introduction of liquid culture and LPA and roll out of Xpert MTB/RIF - current status  2 out of 5 certified DST lab applying liquid culture (MGIT 960 and manual MGIT) Microbiology UI, Jakarta (MGIT 960) and NEHCRI Makassar (Manual MGIT)  Expand TB plan: will support MGIT 960 and HAIN for 2 labs BBLK Surabaya (NRL for culture/DST) and Persahabatan Hospital (MDR TB Treatment Centre)  3 Labs already implemented LPA (Hain test) Microbiology UI, Jakarta; NEHCRI Makassar; Soetomo Hospital, Surabaya  GeneXpert: 17 unit GeneXpert machines and 1700 cartidges have been procured. Implementation of GeneXpert will be done in step wise manner. 5 iniatial sites are operating on March 2012.

Introduction of LPA: Study of GenoType®MTBDR (FL & SL) from HAIN Life Science  The studies are performed in Microbiology, Medical Faculty, University of Indonesia (NRL for TB research and molecular)  GenoType®MTBDRplus evaluation for rapid detection of MDR-TB in TB isolates (phase I)  GenoType®MTBDRplus Evaluation for rapid detection of MDR-TB in patients with sputum smear positive pulmonary TB (phase II)  Performance of Genotype ® MTBDR sl assay for ethambutol, ofloxacin, amikacin and kanamycin resistance testing in MDR and rifampicin resistant M. tuberculosis strains (in progress)

Result of GenotypeMTBDRplus study for rapid detection of MDR-TB in TB isolates (phase I)* Rif resistanceINH resistanceMDR TB Sensitivity90.63%69.49%67.02 % Specificity95.31%92.86%95.45 % PPV96.67%96.47%95.45 % NPV87.14%52.00%67.02 % Notes: Isolates/Strains come from several provinces in Indonesia

On going research of Genotype® MTBDRplus (Phase II) Setting:  300 samples sputum from MDR-TB suspect  Term: Februari 2011-end of March 2012  Compare GenotypeMTBDRplus result with liquid culture (MGIT960)  Observe: Sensitivity, specificity, positive predictive value, and negative predictive value  Data analysis: in progress

On going research of Genotype® MTBDRsl Setting:  235 MDR-TB isolates sample from confirmed MDR-TB patients  Term: August 2011-end of March 2012  Compare GenotypeMTBDRsl with liquid culture (MGIT960).  Observe: sensitivity, specificity, positive predictive value, and negative predictive value  Data: in progress

Introduction of Xpert MTB/Rif (GeneXpert) GeneXpert Implementation Steps Step1: workshop Step 2: select the team Xpert focal person Country GeneXpert Advisory team (C-GAT) Research institutes for OR Step 3: Selection of sites Step 4: developing country specific implementation action plan and agree roles Step 5: develop OR plan and agree on roles Step 6: ToT and training Step 7: implementation

Placement plan of 17 GeneXpert machines 1.Microbiology – UI 2.Persahabatan Hosp 3.Pengoyoman Hosp. (Prison) 1.Soetomo Hosp. 2.BBLK Surabaya 3.Saiful Anwar Hosp. 1.Labuang Baji Hosp. 2.NEHCRI Makassar 1.BLK Papua 1.Adam Malik Hosp 1.Hasan sadikin Hosp. 2.BLK Bandung c 1.Microbiology UGM 1.Moewardi Hosp. 2.Kariadi Hosp. 3.Cilacap Hosp. (Prison) 1.Sanglah Hosp.

Certified DST Lab. for confirmation of Xpert result Adam Malik Hosp. BLK Papua BBLK Palembang BLK SemarangUGM Lab Certified lab Under capacity building process towards certified lab BLK Banjarmasin

GeneXpert Workshop TOT 22

MoU Signing between MoH and GeneXpert Sites 23

GeneXpert On site training 24 Soetomo Hospital Moewardi HospitalPersahabatan Hospital

The Data of Genexpert Examination up to 31 Mar NoSites Date start implementation Number of Suspects MTB positive/ Rif resistant Patient put on treatm ent Remark MDR TB TB HIVTotal 1 Persahabatan Hosp.05 March patient are under evaluation from the clinicians expert team 2Moewardi Hosp.08 March Microbiology UI12 March patient reffer to RS Persahabatan 4Soetomo Hosp.20 March Total

26 The Data of Genexpert Examination up to 30 April 2012 NoSites Date start implementation Number of Suspects MTB positive/Rif resistant Patient put on treatment Remark MDR TB TB HIV MDR TB-HIV Total 1 Persahabatan Hosp.05 March Patient are under evaluation from the clinician expert team 2Moewardi Hosp.08 March Microbiology UI12 March Soetomo Hosp.20 March Patient are under evaluation from the clinician expert team 5 Hasan Sadikin Hosp.03 April Total 20342

The logistic of cartridge 27 Totally number cartridge in wire house (PT Fajar Mas Murni) = 420 The total number of cartridge received for each sites (for examination and Keeping in sites wire house)

Challenges in introduction and roll out of newer diagnostics (LPA &Xpert MTB/RIF)  Expensive machines and consumables.  Quality assurance, maintenance and calibration.  Capacity to treat more MDR TB patients (Human Resources, infrastructure, funding etc)  Availability of SL Drugs, not only in country level but also globally  Limited Quality assured Culture/DST lab to support confirmation of LPA and Xpert TB/Rif result.  Limited MDR TB treatment centre.

Conclusion  TB Laboratory plays main role in MDR TB diagnosis to support PMDT program.  Expansion of quality assured culture/DST lab and MDR TB treatment centre are crucial to achieve national target.  Utilizing new TB diagnostic tools as a breakthrough to avoid delays in treatment.  Increasing in diagnosis capacity must be followed by increasing of treatment capacity as well.

30 Thank You