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New tools & technological frontiers in TB and
M/XDR TB diagnosis
Giorgio RoscignoChair, Stop TB Partnership Working Group
CEO FINDBeijing, 1-3 April 2009
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Outline
• Address the diagnostic gaps
• Review new tools for M/XDR TB and positioning in public health system
• Highlight further technological improvements needed
• Identify medium- and long-term approaches
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New TB Diagnostics: Goals and Objectives
Objectives
• Improving case detection. Sensitive, specific, accessible diagnostics - PHC level
• Rapid, inexpensive detection of drug resistance
• Predictive test: identifying infections that will lead to active disease
Strategy
To co-ordinate and facilitate the development, evaluation and implementation of new and modified diagnostics in a scientifically-acceptable and timely manner by linking all stake-holders involved in the process.
42010 2012 2015
Required expansion of Culture and DST capacity: from 10 to 60 million p/a
# of tests required (million) USD funding
required (million)
2500
2000
1500
1000
500
Required expansion of Smear capacity: from 80 to 200 million p/a
Global laboratory capacity gap:Gap of 120 million smears, 50 million cultures and 5 million drug susceptibility
investigations must be met by 2015, requiring increased investment in laboratory infrastructure
and annual variable cost
USD 2.5 billion required over next 7 years
2008
Urgent
MD
G Targets
200
150
100
50
2 000 biosafety level 3 labs20 000 newly trained technicians
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Diagnostic pipeline accelerated
Recent developments:
At least 20 new technologies in various stages of development and evaluation
Distinct target areas for drug-resistant TB being addressed–Growth and resistance detection–Molecular-based assays
Liquid culture with rapid species identification and line probe assays endorsed by WHO 2007-2008
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Evolution of new TB/MDR TB technologies in the last five years
90 minutesGenotyping
second generation(1st line, Rif & INH)
2010
2days
Line Probe Assay(Genotyping)
(1st line, Rif & INH)2008
15-30 daysLiquid Culture DST
(Phenotyping)(1st/2nd line)
2007
30-60 daysSolid Culture DST
(Phenotyping)(1st/2nd line)
Before 2007
Turnaround timeTechnologyYear
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Evolution of M/XDR testing: decentralizing
2006 2007 2008 2010 2013
Phenotyping:Solid Culture
Phenotyping:Liquid Culture
GenotypingMDR: Line Probe
Assay
Automated Genotyping MDR: Xpert
GenotypingXDR: LPA
Automated Genotyping XDR: Xpert
Manual Genotyping
MDR & XDR: LAMP
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Automated sample prep,
amplification and detection< 120 minutes
Workflow•fully automated with 1-step external sample prep.
•time-to-result 1.5 hrs (walk away test)•throughput: up to 16 tests/module/run•no bio-safety cabinet needed•closed system (no contamination risk)
Performance•specific for MTB•sensitivity similar to culture•detection of rif-resistance via rpoBgene
Automated high tech molecular testing in low tech settings in Demonstration
Xpert
2009 2010
Demonstration AccessSTAGEvaluation
A technology platform for:TB & Rif ResistancePotential for HIV viral loadOther applications
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LAMP demonstration at microscopy center in Mumbai, India
Upstream challenges:Reaching required accuracy& simplicity
Downstream challenges:Implementation of “disruptive”technologyLaboratory preparedness
A technology platform for:TBMalariaHATHIV?Other applications?
2009 2010 2011
Development Demonstration in microscopy centers
AccessSTAGEvaluation
Molecular meets microscopy: TB LAMPin Evaluation
Visual reading of amplified mycobacteria using LAMP
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M/XDR testing on different health care levels
•Surveillance•Reference methods•Network supervision
•Resolution testing(screening-test negative, drug resistance)
•Passive case finding•Detection, drug resistance and treatment
DistrictLevel
MicroscopyLevel
ReferenceLabs
RegionalLabs
Manual molecular testfor case detection
Manual molecular test for MDR & XDR
Solid Culture Liquid cultureLine Probe Assay MDR XDR
Automated PCR MDR XDR
Solid / Liquid culture
Automated PCR MDR XDR
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Current technology gaps
Genotyping for second line drugs(Quinolones, Aminoglycosides)
Line Probe Assay
Automated PCR
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Short and long term approaches for M/XDR testing
2010 20142009 201320122011
Decentralize MDR testing with WHO-endorsed technologies
- Liquid culture & DST from reference toregional labs
- Molecular line probe assay fromreference to regional labs
- Automated molecular from regional todistrict / microscopy labs
Introduce XDR testing on existing technologies
Develop M/XDR testing for microscopy level
- Simplified molecular testing- Other technologies
Two paths to tracking drug resistance globally
Widespread implementation of testing for patient management
Centralized surveillance testing in high throughput
Testing sites
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Thank you