M. Akhalaia, MD, Microbiologist,

Global Consultation on the Implementation of

the Xpert MTB/RIF systemfor rapid diagnosis of TB and MDR-TB

M. Akhalaia, MD, Microbiologist,

Reference Laboratory, National Centre Tuberculosis and Lung Disease, Tbilisi, Georgia

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

1. 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

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)

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 90% 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

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

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

The new DNA test for TB is a fully automateddiagnostic molecular test that usesmodern technology:

Extraction andpurificationDNA/RNA

&

Amplification

&

Multiplexdetection

(automated)

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

Xpert MTB/RIF assay & GeneXpert instrument

• Time to results - 100 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

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

Xpert MTB/RIF assay & GeneXpert instrument

Compared culture

• Sensitivity for AFB+/culture+ 98.2%• Sensitivity for AFB-/culture+ 72.5%• Specificity 99.2%

Rifampicin resistance detection

• Sensitivity – 98%• Specificity – 99%

Xpert MTB/RIF assay & GeneXpert instrument Sensitivity and specificity

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%

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

• 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

Thank you for your attention