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