Download Five components of DOTS

Diagnostics Working Group
29 October 2004
Mark Perkins
Partnership
• Partner academic and national institutions: 20
workplans and activity descriptions
All India Institute of Medical
Sciences
Brazilian National TB Network
Gambia MRC
Industry Partners
Institute for Tuberculosis Research
IUATLD
Johns Hopkins Center for TB
Research
KIT (Royal Tropical Institute)
KIT (Korean Institute of TB)
London School Hyg & Trop Med
MSF
Mycobacteria Reference Lab, NL
Partners in Health
PATH
PHRI
Prince Leopold Institute
of Tropical Medicine
RELACTB
Research Insitute of
Tuberculosis (JATA)
Russian Research
Center for Molecular
Diagnostics
SA MRC
Sequella Foundation
Statens Serum Institut
Stanford Center for TB
Research
Swedish Institute for
Infectious Disease Control
TBRU
TDR
TRC
US CDC Div TB Elimination
US CDC National Center for
Infectious Diseases
US FDA
US NIH-NIAID
ZAMBART
• Industry partnership: ~ 50 groups
• Other fora: CDC/NIH, EC, KIT, Wellcome, IUATLD
What’s missing?
• Coordinated strategy for tool-directed research
• Coordination of field site strengthening
• Diagnostic trial registration and standardization
• Consensus on phase IV research priorities
Designated funding needed for these
activities
DOTS expansion has not improved
case detection rates
No of countries
implementing
DOTS
250
100 Global case
90 notification rate
80 (All forms of TB)
70
60
50
40
30
20
10
0
Total number of countries
200
150
100
50
00
20
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
19
Year
90
0
Global CNR
Countries
Clear need to enhance case detection
to attain global TB control targets
Source:
WHO Report 2003: Global Tuberculosis Control: surveillance, planning, financing. WHO, 2003.
Inefficiency of global TB case detection: 2004
16%
56%
28%
AFB+ detected
AFB+ undetected
AFB negative
Total
1,421,467
2,465,533
4,910,000
8,797,000
Recent history of public sector TB diagnostic
development
• Years of denial: 1975 to 1996
“Microscopy is all we need”
• Years of waiting: 1997 to 2003
“Facilitating industry will provide the tools”
• Years of action: 2004 to 2009
“Medical need – evidence – partnership”
Development of new technologies
Harvesting the best of both worlds to produce public sector goods
Private sector
Public sector
• Market-driven
• Financing
• Product focus
• Manufacture &
Distribution
• IP management
•Needs driven
• Goal-directed R&D
•Altruism
• Complex project
management
•Partnership
1900
1950
• Rigid
targets/milestones
• Marketing
Publicprivate
partnership
•Industry
model +
•Need-driven
•Partnership
2000
FIND will drive diagnostics development from concept to
delivery in the health system
FIND’s focus
Upstream
Discovery
and research
Development
Liaise with funders, pharmaceutical
and biotech companies, research
institutions, academia
July 22nd, 2003
Facilitate,
co-fund,
co-develop
Demonstratio
n
Create network of public and private partners
to create effective tests and demonstrate their
success
Development
Proof of
principle
Evaluation
Downstream
Regulatoryquality
lab & field
trials
FIRST BOARD MEETING
Geneva, Switzerland
Liaise with funders, multi-lateral
agencies, NGOs,health ministries,
and agencies like GDF and
GFATM
Demonstration
Evaluation
Product
in box
Market access
and distribution
Efficacy
Data
Large-scale
projects
Effectiveness
measuring
Data
feasibility and
impact on
disease control
programs
Policy
Virtual development
Manage portfolio of development, evaluation, and demonstration projects
Develop
Evaluate
Demonstrate
Specimen
Bank
Specimen/strain
Bank
Technical
support to NTPs
Strain Bank
Trial site
support
Usage Guidelines
Market
Analysis
Mathematical
modelling
Standardized
protocols
Regulatory
harmonization
Access
assistance
Operational
research
Enabling Infrastructure
Provide intellectual and material infrastructure for diagnostics development
Priority needs for TB diagnostics
Purpose
Case Detection
Drug susceptibility testing
Latent TB Infection
Test Indications
Proposed
Priority
• Detect pulmonary TB with high bacterial load (SS+)
#1
• Detect pulmonary TB with low bacterial load (SS -, Cx +)
#2
• Detect extra-pulmonary and pediatric TB
#3
• Detect MDR-TB for treatment
#4
• Detect MDR-TB for surveillance
#7
• Detect LTBI for surveillance
#5
• Detect LTBI for treatment
#6
Segmentation - diagnostic question vs. health system level
diagnostic
question
health
system level
1. Detection
2. Resolution
3. Surveillance
• Who shall be treated?
• Is patient responding
• Change treatment for failure?
• Are programs effective?
• Are there new strains?
• Is the strain resistant?
• QC procedures &
policies
• strain typing
Central lab
District lab
Health Center
(Clinic)
• fill detection gap
• resolve unclear cases
• resistance testing
• Yes–No answer
• medical monitoring
RESOLUTION
faster than
culture !
DETECTION
more sensitive
than smear !
July 22nd, 2003
FIRST BOARD MEETING
Geneva, Switzerland
• easy & robust lab
procedures
• support for multiple
health problems
• universal platforms
• dedicated POC
devices
• minimal skill
requirements
Tests that revolutionize
patient care or disease control
• POC smear replacement
• POC culture replacement
• 2-day high-TP sensitive lab
test for case detection +/DST for urban centers
Tests that are significant
incremental improvements
over existing tools
• 2-day lab-free culture
replacement
• Specific predictor of
progression from LTBI
• Improved microscopy
• Simplified or speeded culture
• Simplified or speeded DST
POSITIVE
• POC smear supplement
NEGATIVE
2003
2004
2005
2006
2007
2008
Improving
sputum
microscopy
1- Fluorescence
6- Phenol
2- Polycarbonate filters
7- UPS
3- Immunosedimentation
8- NaOCl
4- Magnetic beads
9- CB-18
5- Chitin
10- Silica
TDR RFA
Immunomagnetic separation of mycobacteria from sputum
for improved fluorescent microscopy
Programmatic use of improved microscopy - differential
impact on well and poorly functioning laboratories
Improving the sensitivity of microscopy with a modified
membrane filter method to diagnose pulmonary TB
Multicentric evaluation of a smear microscopy techniques for
the detection of acid-fast bacilli in sputum specimens
Evaluation of sputum concentration methods for diagnosis of
new pulmonary tuberculosis cases by microscopy
Point of care
Skin test
Sequella
Ag detection
Chemogen, GoSensor, Chembio,
Lionex, DOE, KIT, Proteomesystems
Aerosol
Scensive, Mensanna,
Rapid Biosensors
Microscopy
Baldingerst, O’Connell, Xytron
Ab detection
Corixa/IDRI, SSI, NYU,
VictoriaU, CSU
Molecular
Cepheid, Takara, GenProbe, Roche,
Eiken, Idaho, Innogenetics, Investogen
Phage
Biotec, Microphage, Sequella
Culture
BD, Biotest, Salubris
District lab
Colorimetric solid media
Detection speed
LJ
28d
BACTEC
10d
TK
14d
Contamination
Mycobacterial growth
Phage replication assay for detection or DST
TB bacilli
Actiphage
INFECTION
TREATMENT WITH
VIRUSOL
Phage start to
replicate in
cells
NEUTRALISATION
OF VIRUSOL AND
ADDITION OF
SENSOR CELLS
Sensor
cells
POSITIVE
NEGATIVE
PLATING OF
MIXTURE IN A
PETRI DISH AND
OVERNIGHT
INCUBATION
Sensor
cells
Sensor
cells
Sensor
cells
Sensor
cells
Upstream
FIND’s focus
Discovery
and research
Development
Liaise with funders, pharmaceutical
and biotech companies, research
institutions, academia
Evaluation
Downstream
Demonstration
Create network of public and private
partners to create effective tests and
demonstrate their success
Market access
and distribution
Liaise with funders, multi-lateral
agencies, NGOs,health ministries,
and agencies like GDF and GFATM
Exploiting technology for the public good
From concept to affordable delivery in the health system
Proof of
principle
Research
Development
Evaluation
Facilitate,
co-fund,
co-develop
Regulatoryquality
lab & field
trials
Product
in box
Demonstration
Efficacy
Data
Large-scale
projects
measuring Effectiveness
Data
feasibility and
impact on
disease control
programs
Policy
2004-2008 Portfolio
2004
Planning
Antigen detection
Simple NAAT
Development
Phage detection
MGIT case detection
TB serology
Evaluation
Demonstration
Market
2005
2006
2007
2008
Phage detection
Simple NAAT
Antigen detection
TB serology
Simple NAAT
Antigen detection
Simple NAAT
Antigen detection
Phage DST
TK media
MPT64 patch test
TK media
MPT64 patch test
Phage detection
TK media
TB serology
MPT64 patch test
MGIT case detection
Simple NAAT
Antigen detection
T-spot TB
QuantiferonGold
MGIT DST
Phage DST
T-spot TB
Quanitiferon Gold
MGIT DST
MGIT case detection
T-spot TB
Quanitiferon Gold
Phage detection
TK media
TB serology
MPT64 patch test
MGIT case detection
MGIT case detection
MGIT DST
Phage DST
Quanitiferon Gold
T-spot TB
Urban NAAT
Phage detection
TK media
TB serology
MPT64 patch test