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Dr Karin Weyer
Stop TB Department Geneva, Switzerland
Strategic guidance on the useof laboratory technologies
Strategic guidance on the useof laboratory technologies
DEWG Meeting, Geneva: 13 October 2009
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OutlineOutline
Outline of diagnostic and laboratory gaps
Addressing these gaps
WHO policy development process
Policy framework for use of new WHO-endorsed technologies
Urgent actions needed at global and country level
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Latest global TB estimates - 2007Latest global TB estimates - 2007
Estimated number of
cases
Estimated number of
deaths
1.77 million1.77 million(27 per (27 per 100,000)100,000)
9.27 million9.27 million(139 per (139 per 100,000)100,000)
150,000 511,000
All forms of TB Greatest number of cases in Asia; greatest rates per capita in Africa
Multidrug-resistant TB (MDR-TB)
Extensively drug-resistant TB (XDR-TB)
50,000 30,000
HIV-associated TB 1.4 million
456,000
(Updated February 2009)
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Overall problem: MDR-TB diagnostic and treatment levels far too lowOverall problem: MDR-TB diagnostic and treatment levels far too low
511,000 estimated cases annually
Diagnosed and treated in Green Light Committee programmes
Countries report diagnosis and treatment, standard unknown
No diagnosis and treatment reported. Some treatment probably obtained, quality unknown
3%
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DOTS expansion needsDOTS expansion needs
• Increased case detection towards universal access
• HIV- associated and drug resistant TB integrated into routine NTP programmes
Increased managerial and programmatic capacity
Increased access to affordable quality-assured anti-TB drugs
Models of care based on innovative frameworks
underpinned by
Laboratory strengthening
6 |2010 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: fro
m 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 infrastructureand annual variable cost
USD 6.1 billion required by 2015
2008
Urg
ent
MD
G T
argets
200
150
100
50
2,000 biosafety level 3 labs20,000 newly trained technicians
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Meeting the diagnostic gapMeeting the diagnostic gap
Challenges
Weak health systems Inadequate human resources Lack of recognition of laboratory importance in TB control and weak
communication between NTP and laboratory services, requiring rapid policy change
Biosafety concerns Insufficient financial resources Problems of laboratory availability and accessibility Delay in technology transfer to resource-limited settings No or minimal interaction with private-sector
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Diagnostic pipeline accelerated 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, rapid speciation and line probe assays endorsed by WHO 2007-2008; LED microscopy and selected non-commercial culture and drug susceptibility testing methods expected in 2009
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Need for new diagnostics at each levelNeed for new diagnostics at each level
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Establishing strong partnerships is keyChallenges of implementing new diagnosticsEstablishing strong partnerships is keyChallenges of implementing new diagnostics
Feasibility, contract, development phases
Demonstrationphase
Global Impact
Evaluationphase Access phase
• Evidence for regulatory approval
• Evidence for making policy
• Evidence for scaling up
• Evidence for measuring impact
Moving from demonstration to access and impact requires that new diagnostic tools are integrated into functional laboratory services
Additional components to ensure quality diagnostic services
Essential instruments, reagents, supplies
• Global Policy
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Global Laboratory Initiative
Mission: To serve as a platform of coordination and communication, providing the required infrastructure, focused on TB laboratory strengthening, in the areas of:
Global policy guidance, norms, standards, best practices
Laboratory capacity development Interface with other laboratory networks, enabling integration
Standardised laboratory quality assurance
Facilitating technical assistance
Effective knowledge sharing
Advocacy and resource mobilisation
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Identifying the need
for policy change
Reviewing the evidence
Convening an Expert Panel
Assessing draft policyand guidelines
Formulating anddisseminating policy
WHO policy formulation process
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Recent WHO laboratory policiesRecent WHO laboratory policies
Automated liquid culture and DST (2007): Use of liquid culture systems in the context of a comprehensive country plan for strengthening TB laboratory capacity; in a phased manner starting at national/central reference laboratory level
Rapid speciation (2007): Strip speciation for rapid Mycobacterium tuberculosis from non-tuberculous mycobacteria; established at regional or central reference laboratory level in combination with liquid culture
Line probe assays (2008): Use of line probe assays for rapid detection of R resistance within the context of country plans for MDR-TB management, including development of country-specific screening algorithms and timely access to quality-assured second-line anti-tuberculosis drugs; do not eliminate the need for conventional culture and DST capability; should be phased in, starting at national/central reference laboratory or those with proven molecular capability
Second-line drug susceptibility testing (2008): Reliable and reproducible for injectables and fluoroquinolones; to be conducted in supranational or national/central reference laboratories using standardised methodology and drug concentrations
Available at: http://www.who.int/tb/dots/laboratory/policy/en/print.html
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Policy framework at country levelPolicy framework at country level
• Local epidemiology (TB, HIV, MDR-TB)
• Priorities for case detection
• Local laboratory capacity and networks
• Local laboratory human resources and skills base
• Local treatment policies for MDR-TB
• Financial resources
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Analytical processAnalytical process
• Quantify or estimate TB, TB-HIV and MDR-TB burden
• Identify and target specific patient risk groups
• Quantify or estimate diagnostic need to identify risk groups-Number of suspects to be screened-Number and type of laboratories at each service level
• Estimate budget for comprehensive laboratory services-All core components-Capacity for diagnostic and monitoring-Ancillary laboratory services (eg. biochemistry, haematology)
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Phase 1: Laboratory preparedness– Assessment of TB laboratory networks and diagnostic policies
– Upgrade of laboratory infrastructure and biosafety
– Development and implementation of GLP, SOPS, QA, etc.
– Training of core laboratory staff
– Initiating NTP policy reform on diagnostics
Phase 2: Introduction of new diagnostics– Integration of new diagnostics into NTP policies and procedures
– Procurement and installation of instruments, reagents, and other essential supplies
– Validation of new tools and laboratory performance
Phase 3: Impact assessment– Continued mentoring, technical support and oversight of technology transfer
– Assessment of impact of new diagnostics
Phased approach
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Laboratory algorithmLaboratory algorithm
Starts with
• Screening policy for suspects
• Microscopy services as entry point
Positive Negative
MICROSCOPY(ZN or Fluorescence)
CULTURE(Solid or Liquid)
No result
DRUG SUSCEPTIBILITY TESTING-1st LINE(Solid or Liquid)
No resultPositive Negative
MDR
DRUG SUSCEPTIBILITY TESTING-2nd LINE(Solid or liquid)
XDR
Susceptible No result
Not XDR, resistant other drugs Susceptible
Not MDR, resistant other drugs
No result
Dis
tric
t N
RL
/re
gio
nal
SR
L/
NR
L
IDENTIFICATION (SPECIATION)(Conventional/Commercial)
AFB
TB/NTM
Positive Negative
MICROSCOPY(ZN or Fluorescence)
CULTURE(Solid or Liquid)
No result
DRUG SUSCEPTIBILITY TESTING-1st LINE(Solid or Liquid)
No resultPositive Negative
MDR
DRUG SUSCEPTIBILITY TESTING-2nd LINE(Solid or liquid)
XDR
Susceptible No result
Not XDR, resistant other drugs Susceptible
Not MDR, resistant other drugs
No result
Dis
tric
t N
RL
/re
gio
nal
SR
L/
NR
L
IDENTIFICATION (SPECIATION)(Conventional/Commercial)
AFB
TB/NTM
LINE PROBE ASSAY
Solid culture
6-8w
1st line DST
3-4w
2nd line DST
3-4w
Microscopy
24h
Liquid culture
2-3w
1st line DST
1-3w
2nd line DST
1-2w
Microscopy
24h
Microscopy
24h
Line probe assay
24h
MDR-TB diagnosis using conventional solid culture and DST
MDR-TB diagnosis using liquid culture and DST
2nd line DST
1-2w
1st line DST
1-2w
MDR-TB diagnosis using line probe assay, liquid culture and DST
Line probe assay
24h
+
- 2nd line DST
1-2w
1st line DST
1-3w
Liquid culture
2-3w
MDR-TB diagnosisafter 9 to 12 weeks
MDR-TB diagnosisafter 1 to 2 days
MDR-TB diagnosisafter 3 to 5 weeks
MDR-TB diagnosisafter 3 to 5 weeks
Solid culture
6-8w
1st line DST
3-4w
2nd line DST
3-4w
Microscopy
24h
Liquid culture
2-3w
1st line DST
1-3w
2nd line DST
1-2w
Microscopy
24h
Microscopy
24h
LPA
24h
XDR-TB diagnosis using conventional solid culture and DST
XDR-TB diagnosis using liquid culture and DST
2nd line DST
1-2w
1st line DST
1-2w
XDR-TB diagnosis using line probe assay, liquid culture and DST
LPA
24h
+
- 2nd line DST
1-2w
1st line DST
1-3w
Liquid culture
2-3w
XDR-TB diagnosisafter 12 to 16 weeks
XDR-TB diagnosisafter 4 to 9 weeks
2nd line DST*
3-4w
* Methods not validated or standardised
2nd line DST
1-3w
2nd line DST
1-3w
Liquid culture
2-3w
2nd line DST
1-3w
2nd line DST
1-3w
XDR-TB diagnosisafter 4 to 9 weeks
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Policy considerations Policy considerations Current technologies not mutually exclusive
– Conventional culture capacity required for SM- specimens– Conventional DST capacity required to detect XDR-TB
Liquid culture and line probe assay considered as gold standards, to be phased in without loss of existing solid culture and DST capacity
LED microscopy as alternative for both fluorescence and conventional light microscopy (pending STAG endorsement)
Selected non-commercial culture and DST methods not alternatives for gold standards, but may provide interim solution (pending STAG endorsement)
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Urgent actions needed Urgent actions needed
Increased political commitment
Accelerated policy change (with lab expert involvement)
National laboratory strategic plans
Laboratory human resource plans
Increased and sustained donor funding
Novel approaches to technical assistance
Increased research to develop point of care tests
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‘From unimaginable…to indispensable’
Strengthening TB laboratoriesStrengthening TB laboratories
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• WHO-STB laboratory staff
• WHO Expert Groups
• WHO Strategic and Technical Advisory Group for TB (STAG-TB)
• Global Laboratory Initiative (GLI) Core Group
• GLI Technical Working Groups
• GLI Partners involved in laboratory strengthening
• FIND
AcknowledgementsAcknowledgements