Transcript Guidelines - Stop TB Partnership

Strategic guidance on the use
of laboratory technologies
Dr Karin Weyer
Stop TB Department Geneva, Switzerland
1|
DEWG Meeting, Geneva: 13 October 2009
Outline

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
2|
Latest global TB estimates - 2007
(Updated February 2009)
Estimated
number of
cases
All forms of TB
Greatest number of cases in Asia;
greatest rates per capita in Africa
9.27 million
1.77 million
(139 per 100,000)
(27 per 100,000)
Multidrug-resistant
TB (MDR-TB)
511,000
Extensively drugresistant TB (XDR-TB)
50,000
HIV-associated TB
3|
Estimated
number of
deaths
1.4 million
150,000
30,000
456,000
Overall problem:
MDR-TB diagnostic and treatment levels far too low
No diagnosis and treatment
reported. Some treatment probably
obtained, quality unknown
511,000
estimated
cases
annually
Countries report diagnosis and
treatment, standard unknown
3%
4|
Diagnosed and treated in Green
Light Committee programmes
DOTS 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

5|
Laboratory strengthening
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 6.1 billion required by 2015
# of tests required
(million)
USD funding
required
(million)
200
2500
2,000 biosafety level 3 labs
20,000 newly trained technicians
100
MDG Targets
150
2000
1500
1000
Urgent
50
6|
2008
2010
2012
2015
500
Meeting the diagnostic gap
Challenges








7|
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
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
8|
Need for new diagnostics at each level
9|
Establishing strong partnerships is key
Challenges of implementing new diagnostics
Feasibility,
contract,
development
phases
Evaluatio
n
phase
• Evidence for
regulatory
approval
Moving from demonstration to
access and impact requires that
new diagnostic tools are integrated
into functional laboratory services
Demonstrati
on
phase
• Evidence for
making
policy
• Global Policy • Evidence for
scaling up
Logistics and supplies
Human Resources
(Guidelines
Technology transfer)
Essential instruments,
reagents, supplies
10 |
Glob
al
Impa
ct
Access
phase
Infrastructure
• Evidence for
measuring
impact
Quality Assurance
Linked referral
systems and reporting
Additional components to ensure quality
diagnostic services
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
11 |
WHO policy formulation process
Identifying the need
for policy change
Reviewing the evidence
Convening an Expert Panel
Assessing draft policy
and guidelines
Formulating and
disseminating policy
12 |
Recent 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 nontuberculous 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 countryspecific 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
13 |
Policy framework at country level
•
•
•
•
•
•
14 |
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
Analytical process
•
•
•
•
15 |
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)
Phased approach
 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
16 |
Laboratory algorithm
Starts with
• Screening policy for suspects
• Microscopy services as entry point
17 |
District
MICROSCOPY
(ZN or Fluorescence)
Positive
Negative
No result
AFB
NRL/regional
CULTURE
(Solid or Liquid)
Positive
DRUG SUSCEPTIBILITY TESTING-1st LINE
(Solid or Liquid)
MDR
SRL/NRL
Negative
Not MDR, resistant other drugs
No result
IDENTIFICATION (SPECIATION)
(Conventional/Commercial)
TB/NTM
Susceptible
No result
Susceptible
No result
DRUG SUSCEPTIBILITY TESTING-2nd LINE
(Solid or liquid)
XDR
Not XDR, resistant other drugs
District
MICROSCOPY
(ZN or Fluorescence)
Positive
Negative
No result
AFB
CULTURE
(Solid or Liquid)
NRL/regional
LINE PROBE ASSAY
Positive
DRUG SUSCEPTIBILITY TESTING-1st LINE
(Solid or Liquid)
MDR
SRL/NRL
Negative
Not MDR, resistant other drugs
No result
IDENTIFICATION (SPECIATION)
(Conventional/Commercial)
TB/NTM
Susceptible
No result
Susceptible
No result
DRUG SUSCEPTIBILITY TESTING-2nd LINE
(Solid or liquid)
XDR
Not XDR, resistant other drugs
MDR-TB diagnosis using conventional solid culture and DST
Microscopy
Solid culture
1st line DST
2nd line DST
24h
6-8w
3-4w
3-4w
MDR-TB diagnosis
after 9 to 12 weeks
MDR-TB diagnosis using liquid culture and DST
Microscopy
Liquid culture
1st line DST
2nd line DST
24h
2-3w
1-3w
1-2w
MDR-TB diagnosis
after 3 to 5 weeks
MDR-TB diagnosis using line probe assay, liquid culture and DST
Line probe assay
Microscopy
24h
24h
Line probe assay
24h
+
-
2nd line
DST
MDR-TB
diagnosis
after 1 to1-2w
2 days
Liquid
culture
1st
line DST
1st line DST
2nd
2-3w
1-2w
1-3w
1-2w
MDR-TB diagnosis
after 3 to 5 weeks
XDR-TB diagnosis using conventional solid culture and DST
Microscopy
Solid culture
1st line DST
2ndline
lineDST*
DST
2nd
24h
6-8w
3-4w
3-4w
3-4w
XDR-TB diagnosis
after 12 to 16 weeks
* Methods not validated or standardised
XDR-TB diagnosis using liquid culture and DST
Microscopy
Liquid culture
1st line DST
2nd
2nd line
line DST
DST
24h
2-3w
1-3w
1-3w
1-2w
XDR-TB diagnosis
after 4 to 9 weeks
XDR-TB diagnosis using line probe assay, liquid culture and DST
LPA
Microscopy
24h
24h
LPA
24h
+
Liquid culture
2nd
line
DST
2nd
2nd
line
line
DST
DST
2-3w
1-3w
1-3w
1-2w
-
Liquid culture
DST
1st 1st
lineline
DST
2nd
2nd line
line DST
DST
2-3w
1-2w1-3w
1-3w
1-2w
XDR-TB diagnosis
after 4 to 9 weeks
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)
22 |
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
23 |
Strengthening TB laboratories
‘From unimaginable…to indispensable’
24 |
Acknowledgements
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•
•
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•
25 |
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