1

Introduction 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 MONITORINGJakarta, Indonesia, 29-31 May 2012

Background2

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 ServicesAt 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/Services4

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 1st and 2nd line DST.

1. BBLK Surabaya, East java2. Microbiology UI, Jakarta3. RS Persahabatan, Jakarta4. 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 Java South 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 2009 2012

1 National TB Lab action Plan

- Available

2 National TB Reference Lab

- 3 labs

3 Certified FL DST Lab 3 labs 5 labs

4 Certified SL DST Lab - 5 labs

5 Improve Biosafety (Renovation of Culture/DST Lab to meet BSL 2 plus standard)

- 4 labs completed2 labs in progress

6 Implementation of LPA

- 3 labs

7 Implementation of GeneXpert

- 5 labs (up to March)

National TB Lab Action Plan, 2011-2014

9

Cost Sharing in Establishing BSL 2 plus Lab for Culture/DST

10

Lab/Institutio

n

Design Renovation

Equipments

Training Technical

Assistance

Microbiology UGM

TBCAP TBCAP TBCAP TBCAP TBCAPTBCARE I

BLK Semarang

TBCAP APBD, TBCAP

APBN, TBCAP, GF-ATM

TBCAP TBCAP TBCARE I

BLK Jayapura

TBCAP TBCAP APBN, TBCAP, GF-ATM

TBCAP, GF-ATM

TBCAP TBCARE I

Adam Malik Hospital

TBCAP GF-ATM GF-ATM TBCAP, GF-ATM

TBCAP TBCARE I

BLK Banjarmasin

GF-ATM GF-ATM APBNGF-ATM

TBCAP, GF-ATM

TBCAP TBCARE I

Renovation of TB Culture/DST Lab:

Microbiology UGM 11

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Renovation of TB Culture/DST Lab:

BLK Jayapura, Papua

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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® MTBDRsl 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 resistanc

e

INH resistance

MDR TB

Sensitivity

90.63% 69.49% 67.02 %

Specificity

95.31% 92.86% 95.45 %

PPV 96.67% 96.47% 95.45 %

NPV 87.14% 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 sitesStep 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 – UI2. Persahabatan Hosp3. Pengoyoman Hosp. (Prison)

DKI Jakarta

South Sulawesi

1. Soetomo Hosp.2. BBLK Surabaya3. Saiful Anwar Hosp.

1. Labuang Baji Hosp.2. NEHCRI Makassar

Papua

1. BLK Papua

Nort Sumatera

1. Adam Malik Hosp

1. Hasan sadikin Hosp.2. BLK Bandung

c

1. Microbiology UGM

DIY

West Java

Central Java

1. Moewardi Hosp.2. Kariadi Hosp.

3. Cilacap Hosp. (Prison)

Bali

East Java

1. Sanglah Hosp.

Certified DST Lab. for confirmation of Xpert result

Microbiology - UI

DKI Jakarta

BLK BandungPersahabatan Hosp.

West Java

East Java South Sulawesi

BBLK Surabaya NEHCRI Makassar

North Sumatera

Adam Malik Hosp.

Papua

BLK PapuaSouth Sumatera

BBLK PalembangCentral Java

BLK Semarang

DIY

UGM

Province

Lab

Lab

ProvinceCertified lab

Under capacity building process towards certified lab

South KalimantanBLK Banjarmasin

GeneXpert Workshop TOT22

MoU Signing between MoH and GeneXpert Sites

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GeneXpert On site training

24Soetomo Hospital

Moewardi Hospital Persahabatan Hospital

The Data of Genexpert Examination up to 31 Mar 2012

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No SitesDate start

implementation

Number of Suspects MTB

positive/Rif

resistant

Patient put

on treatment

Remark

MDR TB

TB HIV Total

1Persahabatan Hosp.

05 March 2012  69  0 69 31 16

15 patient are under

evaluation from the clinicians expert team

2Moewardi Hosp.

08 March 2012 18 3 21 6 6

3Microbiology UI

12 March 2012 0 18 18 1 1

1 patient reffer to RS

Persahabatan

4Soetomo Hosp.

20 March 2012 4 2 6 2 2

  Total       11440

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The Data of Genexpert Examination up to 30 April 2012

No SitesDate start

implementation

Number of Suspects MTB

positive/Rif

resistant

Patient put on

treatment

Remark

MDR TB

TB HIV

MDR TB-HIV

Total

1Persahabatan Hosp.

05 March 2012 59 0 0 59 21 7

14 Patient are under

evaluation from the clinician

expert team

2Moewardi Hosp.

08 March 2012 27 2 2 31 4 4

3Microbiology UI

12 March 2012 0 48 0 48 0 0

4 Soetomo Hosp.20 March

2012 29 10 0 39 15 5

10 Patient are under

evaluation from the clinician

expert team

5Hasan Sadikin Hosp. 03 April 2012 7 19 0 26 2 2

  Total   203 42

The logistic of cartridge27

Sites Total number of

cartridge received

Micro UI 260

Persahabatan Hospital 240

RSUD DR Moewardi 220

RSUD DR Soetomo 340

RS Hasan Sadikin 220Totally number cartridge distribution 1280

• 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.

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Thank You