1. Global Consultation on the Implementation of the Xpert MTB/RIF system for rapid diagnosis of TB and MDR-TB
M. Akhalaia, MD, Microbiologist,
Reference Laboratory, National Centre Tuberculosis and Lung Disease, Tbilisi, Georgia

2. Global Consultation on the implementation of Xpert MTB/RIF System for rapid daignosis of TB and MDR-TB
30 Nov-2 Dec 2010
(Geneva, Switzerland)
Meeting objectives
Diagnostic algorithms for risk groups
2. Programmatic implementation: tiered lab services
3. Pricing considerations and market dynamics
4. Cost-effectiveness and cost-benefit considerations
5. Global framework for rapid uptake in countries
WHO Policy announcement: 7 Dec 2010

3. WHO recommendations 2006-2010 2007 Comercial liquid culture/DST
Rapid speciation (MPT64)
2008
Line probe assay (Rif&INH)
2009
LED-based FM
Non-commercial culture (MODS, CRI, NRA)
2010
- Catrige-based Automated NAAT(Xpert MTB/RIF)

5. To face the burden of TB, TB/HIV and especially MDRTB, we need a rapid test for TB and drug susceptibility The detection of RIF resistance may be a good surrogate marker for MDR-TB, as an estimated % or RIF-resistant TB is also resistant to INH In the past 4 years, WHO has worked intensively with FIND, UNITAID, USAID and other partners to pursue new TB diagnostics and rapid uptake at country level

6. Xpert MTB/RIF assay & GeneXpert instrument
The rapid test:
Detects M. tuberculosis and RIF resistance by PCR amplification
Process is hemi nested and the amplified target is detected in real time by six color fluorescent molecular beacons

7. Xpert MTB/RIF assay & GeneXpert instrument

8. Xpert MTB/RIF assay & GeneXpert instrument

9. Xpert MTB/RIF assay & GeneXpert instrument

10. Xpert MTB/RIF assay & GeneXpert instrument

11. Xpert MTB/RIF assay & GeneXpert instrument
The new DNA test for TB is a fully automated
diagnostic molecular test that uses
modern technology:
Extraction and
purification
DNA/RNA
&
Amplification
Multiplex
detection
(automated)

12. Xpert MTB/RIF assay & GeneXpert instrument

13. Xpert MTB/RIF assay & GeneXpert instrument

14. Xpert MTB/RIF assay & GeneXpert instrument

15. Xpert MTB/RIF assay & GeneXpert instrument

16. Xpert MTB/RIF assay & GeneXpert instrument

17. Xpert MTB/RIF assay & GeneXpert instrument

18. Xpert MTB/RIF assay & GeneXpert instrument

19. Xpert MTB/RIF assay & GeneXpert instrument

20. Xpert MTB/RIF assay & GeneXpert instrument
Time to results minutes
Throughput - Total hands-on time of 2 min, total daily throughput depends on the size of instrument (4 cartridges system – up to 16 tests)
Specimen type – Sputum, may work with other simples except for venous blood
Sample preparation – Two steps
Biosafety level - Level 1
Readout – Simple and color coded, readout on a computer
Waste disposal – Plastic reagents tubes can recycled, cartridges can be incinerated

21. Xpert MTB/RIF assay & GeneXpert instrument
Closed system – no contamination risk
Controls – Positive control included in test kit
Reagents – All reagents in self-contains kit, kit contains a pipette to transfer liquid sputum from container to cartridge
Storage/stability (including reagents) – Maximum shelf-life of 14 months
Reagents stable at temperature 2-280
Instrumentations – Requires annual maintenance
Power requirement – Low power requirement compared with other PCR system
Training – Approximately 1 day of training required

22. Xpert MTB/RIF assay & GeneXpert instrument Sensitivity and specificity
Compared culture
Sensitivity for AFB+/culture %
Sensitivity for AFB-/culture %
Specificity %
Rifampicin resistance detection
Sensitivity – 98%
Specificity – 99%

23. Xpert MTB/RIF assay & GeneXpert instrument
Projected prices reductions based on increases in the number of tests
Year
2011
2012
2014
Number of tests (million)
0.6m
1.7m
3.7m
Price per Test
$16.86
$14.00
$10.72
Average Price Reduction
75%
79%
84%

24. RECOMMENDATIONS
• In high MDR-TB settings: Persons at risk of MDR-TB (treatment failures, other retreatment cases, close contacts of MDR-TB cases) should be tested using Xpert MTB/RIF as the primary diagnostic test; Strong recommendation
• In high HIV prevalence settings: Persons living with HIV who have signs and symptoms of TB, those seriously ill and suspected of having TB regardless of HIV status, and those with unknown HIV status presenting with strong clinical evidence of HIV infection, should be tested using Xpert MTB/RIF as the primary diagnostic test; Strong recommendation
In other settings: Xpert MTB/RIF is recommended as the primary diagnostic test where available, including in persons living with HIV in these settings, or as a follow-on test (at higher level of the health service) after screening by sputum smear microscopy (at lower level of the health service) or after screening by chest radiology; Conditional recommendation

25. • Access to conventional microscopy, culture and DST is still needed
• Recommendations apply to the use of Xpert
MTB/RIF in sputum specimens
• Recommendations support the use of one sputum specimen

26. Thank you for your attention