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
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
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)
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
Sensitivity and specificity
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
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
$16.86
$14.00
$10.72
75%
79%
84%
Price per Test
Average Price Reduction
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