This document discusses future research priorities for tuberculosis control post-2015. It outlines the rationale for developing a new global TB strategy after 2015, including addressing challenges like case detection, TB/HIV co-infection, and drug-resistant TB. Six categories of TB research are identified: epidemiology, fundamental research, diagnostics, treatment, vaccines, and operational research. Key areas for future research include developing new diagnostics, drugs, vaccines, and optimizing case detection and treatment delivery. Funding for TB research needs to increase to develop innovative tools and strategies to work towards a world free of TB.

1. FUTURE RESEARCH MOVEMENT
FOR TUBERCULOSIS CONTROL
FUTURE RESEARCH MOVEMENT
FOR TUBERCULOSIS CONTROL
A/Prof. Nguyen Viet Nhung, MD., PhD
Vice director, National Lung Hospital, Hanoi, Viet Nam
Deputy Manager, National Tuberculosis control Program
Vice President, Viet Nam Association against TB and Lung Diseases
Regional Green Light Committee - WHO / WPR

4. Looking beyond 2015:
Rationale
At the 65th World Health Assembly in May 2012, Member States called upon WHO to
develop a new post-2015 TB strategy and targets and present this to Member States at
the 67th World Health Assembly in 2014. Some States also urged WHO to start the
formal process through the Executive Board and World Health Assembly in 2013.

5. Start Developing
Draft Global strategy
for TB prevention, treatment and care
post-2015
Dr Malgosia Grzemska
Stop TB Department
World Health Organization
TAG TB/WPRO
Phnom Penh, Cambodia, 23-25 October 2012

6. Moving towards a new approach:
Addressing the most vulnerable
Half a million women and
over 70,000 children die of
TB each year; 10 million
“TB” orphans
Poor, crowded & poorly ventilated
settings
TB linked to HIV infection, malnutrition,
alcohol, drug and tobacco use, diabetes
Half a million women and
over 70,000 children die of
TB each year; 10 million
“TB” orphans
Migrants, prisoners, minorities,
refugees face risks, discrimination
& barriers to care

7. Moving towards a new approach:
Addressing key challenges
Case detection
A third of cases not
diagnosed/reported
TB/HIV co infection
Special challenge in Africa
Multidrug - resistant TB
Special challenge in Eastern
Europe
Bottlenecks for financing of
research and innovation
Case detection
A third of cases not
diagnosed/reported
TB/HIV co infection
Special challenge in Africa
Multidrug - resistant TB
Special challenge in Eastern
Europe
Weak health policies,
systems, financing, and
services
Under-engaged
communities and
providers

8. The way forward:
Expansion with Innovation
• Greater commitment
• Active case finding
• Molecular diagnosis
• Treat all forms of TB
• Treatment of latent TB
• Research and
innovation
• Much greater engagement of
all providers and community
• Much stronger system support
• Social protection
• Whole-of-government
approach
• Major drive for Innovation
More and Better
Stop TB Strategy
• (Enhanced and)
innovative TB
care/DOTS
• Bold policies and
supportive systems
• Intensified research
and innovation
• Greater commitment
• Active case finding
• Molecular diagnosis
• Treat all forms of TB
• Treatment of latent TB
• Research and
innovation
More and
Better DOTS
• Much greater engagement of
all providers and community
• Much stronger system support
• Social protection
• Whole-of-government
approach
• Major drive for Innovation
• (Enhanced and)
innovative TB
care/DOTS
• Bold policies and
supportive systems
• Intensified research
and innovation
Post-2015
TB Strategy

9. Proposed three pillars
Establishing a
new post-2015 strategy
Innovativ
e TB Care
Bold
policies and
supportive
systems Intensified
research
and
innovation
WHOandPartnersSupporttocountries
Surveillance,MonitoringandEvaluation
Intensified
research
and
innovation
WHOandPartnersSupporttocountries
Surveillance,MonitoringandEvaluation

10. Innovative TB Care
Bold policies and
supportive systems
Intensified Research
Vision: A world free of TB
DRAFT Post-2015 TB Strategy
CORE PRINCIPLES:
Government stewardship with adequate financing
Engagement of communities and civil society; Collaboration with private sector
Promotion of human rights, ethics and equity
Adaptation of the strategy and targets at country level
Monitoring and evaluation across all strategy components
Innovative TB Care
Rapid diagnosis and systematic
screening of contacts and other
high-risk populations
Treatment of all forms of TB with
patient support
Management of drug-resistant TB,
TB/HIV and other co-morbidities
Preventive treatment of high-risk
populations
Bold policies and
supportive systems
Policies pursuing a system-wide
approach for integration of TB care in
all health services
Universal Health Coverage with free
TB care and social protection
Regulatory framework including vital
registration, mandatory case-
notification, infection control and
rational use of quality-assured drugs
Whole-of-government approach to
addressing social determinants of TB
including poverty reduction, food
security, healthy living and working
conditions
Intensified Research
Discovery, development and rapid
uptake of new diagnostics, drugs
and vaccines
Research to optimize
implementation and adopt
innovations
Sept 2012

11. Six categories of
TB Research
1. Epidemiology
2. Fundamental research
3. Diagnostics
4. Treatment
5. Vaccines
6. Operational and
public health research
1. Epidemiology
2. Fundamental research
3. Diagnostics
4. Treatment
5. Vaccines
6. Operational and
public health research

12. 1. Epidemiology
– Determine the burden of TB
– Understand variations in the dynamics of TB in
different settings and identify the social and
biological drivers of M. tuberculosis transmission
at population level
2. Fundamental research
– Characterize human TB by modern biochemical,
clinical and epidemiological approaches
– Better understand the host–pathogen interaction
– Use ‘discovery science’ to identify biomarkers
that can better differentiate the stages of the
disease spectrum.
1. Epidemiology
– Determine the burden of TB
– Understand variations in the dynamics of TB in
different settings and identify the social and
biological drivers of M. tuberculosis transmission
at population level
2. Fundamental research
– Characterize human TB by modern biochemical,
clinical and epidemiological approaches
– Better understand the host–pathogen interaction
– Use ‘discovery science’ to identify biomarkers
that can better differentiate the stages of the
disease spectrum.

13. 3. Diagnostics
– Evaluate biomarkers identified in fundamental
studies for use as diagnostic tools
– Design and validate a set of tools for diagnosis of
active drug-sensitive and drug-resistant TB and
latent TB infection that are feasible and applicable
at various health-care levels in high-burden settings
– Improve existing diagnostic tests for active drug-
sensitive and drug-resistant TB and latent TB
infection at various health-care levels in high-
burden settings
– Evaluate new diagnostic tools, and conduct
demonstration studies, followed by evaluation of
the programmatic impact of all diagnostic tools
3. Diagnostics
– Evaluate biomarkers identified in fundamental
studies for use as diagnostic tools
– Design and validate a set of tools for diagnosis of
active drug-sensitive and drug-resistant TB and
latent TB infection that are feasible and applicable
at various health-care levels in high-burden settings
– Improve existing diagnostic tests for active drug-
sensitive and drug-resistant TB and latent TB
infection at various health-care levels in high-
burden settings
– Evaluate new diagnostic tools, and conduct
demonstration studies, followed by evaluation of
the programmatic impact of all diagnostic tools

14. 4. Treatment
– Develop new drugs and treatment strategies
– Develop a shorter regimen for drug-susceptible TB
that can be used in combination with HIV
treatment
– Develop a safer, more efficacious, shorter regimen
for drug-resistant TB that is compatible with HIV
treatment
– Develop safe, reliable, user-friendly drug regimens
suitable for all forms of TB in children and
compatible with HIV treatment
– Develop safer, more effective, shorter regimens for
TB infected individuals
– Develop safer, shorter, highly effective regimens
for drug-susceptible and drug-resistant latent TB
infection that are compatible with HIV treatment
and suitable for children
4. Treatment
– Develop new drugs and treatment strategies
– Develop a shorter regimen for drug-susceptible TB
that can be used in combination with HIV
treatment
– Develop a safer, more efficacious, shorter regimen
for drug-resistant TB that is compatible with HIV
treatment
– Develop safe, reliable, user-friendly drug regimens
suitable for all forms of TB in children and
compatible with HIV treatment
– Develop safer, more effective, shorter regimens for
TB infected individuals
– Develop safer, shorter, highly effective regimens
for drug-susceptible and drug-resistant latent TB
infection that are compatible with HIV treatment
and suitable for children

15. 5. Vaccines
– Conduct fundamental research as a basis for the
development of effective TB vaccines
– Conduct research and clinical testing to better
understand the safety and efficacy of BCG and
candidate vaccines
– Develop standardized assays and find
biomarkers for use in clinical trials to identify
correlates of protection
– Develop new pre- and post-exposure vaccines,
new adjuvants and new delivery platforms
– Improve and standardize preclinical assays to
evaluate immunogenicity and potential
protective efficacy of new TB vaccines
– Improve and standardize testing of TB vaccines
in clinical trials
5. Vaccines
– Conduct fundamental research as a basis for the
development of effective TB vaccines
– Conduct research and clinical testing to better
understand the safety and efficacy of BCG and
candidate vaccines
– Develop standardized assays and find
biomarkers for use in clinical trials to identify
correlates of protection
– Develop new pre- and post-exposure vaccines,
new adjuvants and new delivery platforms
– Improve and standardize preclinical assays to
evaluate immunogenicity and potential
protective efficacy of new TB vaccines
– Improve and standardize testing of TB vaccines
in clinical trials

16. 6. Operational and public health research
– Improve TB case detection and diagnosis
– Investigate methods to improve access to treatment and treatment
delivery for drug-sensitive and drug-resistant TB
– Institute sustainable collaboration with all private and public
providers of TB care and control
– Address priority operational research questions at global, regional or
national level to improve implementation of collaborative TB and
HIV activities, and also in respect of other diseases or conditions in
which the risk for TB is increased
– Design collaborative activities in other disease programmes or
situations in which TB risk is increased
– Investigate methods to encourage community participation, to
increase the effectiveness of all interventions (e.g. case-finding,
access to treatment and care delivery)
– Optimize infection control to reduce TB transmission
– Improve measurement of disease burden by effective surveillance,
monitoring and evaluation of TB programmes
– Ensure that countries have the capacity to perform TB-related
operational research to improve TB programme performance
6. Operational and public health research
– Improve TB case detection and diagnosis
– Investigate methods to improve access to treatment and treatment
delivery for drug-sensitive and drug-resistant TB
– Institute sustainable collaboration with all private and public
providers of TB care and control
– Address priority operational research questions at global, regional or
national level to improve implementation of collaborative TB and
HIV activities, and also in respect of other diseases or conditions in
which the risk for TB is increased
– Design collaborative activities in other disease programmes or
situations in which TB risk is increased
– Investigate methods to encourage community participation, to
increase the effectiveness of all interventions (e.g. case-finding,
access to treatment and care delivery)
– Optimize infection control to reduce TB transmission
– Improve measurement of disease burden by effective surveillance,
monitoring and evaluation of TB programmes
– Ensure that countries have the capacity to perform TB-related
operational research to improve TB programme performance

17. Five priority areas
1. Access, screening and
diagnosis of TB;
2. Sustainable collaboration with
all care-providers for TB
control;
3. Prevention of TB in people
living with HIV, and joint
treatment of HIV and TB;
4. Access to and delivery of
treatment for drug-susceptible
and M/XDR-TB;
5. Capacity-building for
operational research.
1. Access, screening and
diagnosis of TB;
2. Sustainable collaboration with
all care-providers for TB
control;
3. Prevention of TB in people
living with HIV, and joint
treatment of HIV and TB;
4. Access to and delivery of
treatment for drug-susceptible
and M/XDR-TB;
5. Capacity-building for
operational research.

18. KEY FACTS AND MESSAGES ON FUTURE TB RESEARCH
Global TB Report 2012 - WHO
• Develop new TB diagnostics, drugs, and vaccines
• WHO has endorsed several new diagnostic tests
or methods since 2007, including Xpert
MTB/RIF that has the potential to transform TB
care. Other new tests, including point- of- care
tests, are in development.
• 11 vaccine candidates for TB prevention in
Phase I or Phase II trials and one
immunotherapeutic vaccine in a Phase III trial. It
is hoped that one or two of the candidates in a
Phase II trial will enter a Phase III trial in the
next 2–3 years, with the possibility of licensing at
least one new vaccine by 2020.
• Develop new TB diagnostics, drugs, and vaccines
• WHO has endorsed several new diagnostic tests
or methods since 2007, including Xpert
MTB/RIF that has the potential to transform TB
care. Other new tests, including point- of- care
tests, are in development.
• 11 vaccine candidates for TB prevention in
Phase I or Phase II trials and one
immunotherapeutic vaccine in a Phase III trial. It
is hoped that one or two of the candidates in a
Phase II trial will enter a Phase III trial in the
next 2–3 years, with the possibility of licensing at
least one new vaccine by 2020.

20. • 11 new or repurposed anti-TB drugs in clinical trials.
– Phase III trials of 4-month regimens for the treatment of drug-
susceptible TB are expected in 2013.
– 2 new compounds are being evaluated for use as an adjunct to
current optimized regimens for MDR-TB; one compound recently
moved to a Phase III trial and the other is expected to do so before
the end of 2012.
– A new three - drug combination regimen that could be used to
treat both drug-sensitive TB and MDR-TB and shorten
treatment duration has been tested in a Phase II study of early
bactericidal activity, with encouraging results.
• Funding for TB research and development has increased in
recent years, but stagnated between 2009 and 2010. At US$
630 million in 2010, funding falls far short of the annual
target of US$ 2 billion specified in the Global Plan to Stop
TB 2011–2015.
• 11 new or repurposed anti-TB drugs in clinical trials.
– Phase III trials of 4-month regimens for the treatment of drug-
susceptible TB are expected in 2013.
– 2 new compounds are being evaluated for use as an adjunct to
current optimized regimens for MDR-TB; one compound recently
moved to a Phase III trial and the other is expected to do so before
the end of 2012.
– A new three - drug combination regimen that could be used to
treat both drug-sensitive TB and MDR-TB and shorten
treatment duration has been tested in a Phase II study of early
bactericidal activity, with encouraging results.
• Funding for TB research and development has increased in
recent years, but stagnated between 2009 and 2010. At US$
630 million in 2010, funding falls far short of the annual
target of US$ 2 billion specified in the Global Plan to Stop
TB 2011–2015.

21. Lead Optimization
Preclinical
Development
GLP
Tox.
Phase I Phase II Phase III
Delamanid (OPC-67683)
Gatifloxacin
Moxifloxacin
Rifapentine
AZD5847
Bedaquiline (TMC-207)
Linezolid
Novel Regimens2
PA-824
Rifapentine
SQ-109
Sutezolid (PNU-100480)
CPZEN-45
DC-159a
Q201
SQ609
SQ641
Preclinical DevelopmentDiscovery1
Clinical Development
Diarylquinoline
DprE Inhibitors
GyrB inhibitors
InhA Inhibitors
LeuRS Inhibitors
MGyrX1 inhibitors
Mycobacterial Gyrase
Inhibitors
Pyrazinamide Analogs
Riminophenazines
Ruthenium (II) complexes
Spectinamides
Translocase-1 Inhibitors
Global TB Drug Pipeline
BTZ043
TBA-354
AZD5847
Bedaquiline (TMC-207)
Linezolid
Novel Regimens2
PA-824
Rifapentine
SQ-109
Sutezolid (PNU-100480)
CPZEN-45
DC-159a
Q201
SQ609
SQ641
Diarylquinoline
DprE Inhibitors
GyrB inhibitors
InhA Inhibitors
LeuRS Inhibitors
MGyrX1 inhibitors
Mycobacterial Gyrase
Inhibitors
Pyrazinamide Analogs
Riminophenazines
Ruthenium (II) complexes
Spectinamides
Translocase-1 Inhibitors
Chemical classes: fluoroquinolone, rifamycin, oxazolidinone, nitroimidazole, diarylquinoline, benzothiazinone
1 Ongoing projects without a lead compound series can be viewed at http://www.newtbdrugs.org/pipeline-discovery.php.
2 Combination regimens: first clinical trial (NC001) of a novel TB drug regimen testing the three drug combination of PA-824,
moxifloxacin, and pyrazinamide was initiated November 2010 and completed in 2011 with promising results. The second
clinical trial (NC002) of this regimen was launched in March 2012 and will test the efficacy of the regimen in drug-sensitive
and multidrug-resistant patients. The third clinical trial (NC003) will evaluate PA-824, TMC-207, pyrazinamide and
clofazimine in combinations and is scheduled to begin September 2012.
Updated: June 18, 2012
www.newtbdrugs.org
4 Repurposed Drugs
6 New Drugs
3 New Classes
Drugs currently in the regulatory
review process
Drugs currently in the regulatory
review process

23. • TB Diagnosis
– Techniques
– Approach
• Treatment
– Drugs / Regimens
– Delivery Management
• Prevention
– Infection control
– Vaccination
– Preventive therapy
• Specific categories
– Smear negative
– TB/HIV
– Pediatric TB
– M/XDR TB
• Research Partnership
• TB Diagnosis
– Techniques
– Approach
• Treatment
– Drugs / Regimens
– Delivery Management
• Prevention
– Infection control
– Vaccination
– Preventive therapy
• Specific categories
– Smear negative
– TB/HIV
– Pediatric TB
– M/XDR TB
• Research Partnership

24. Acknowledgements
• WHO/Stop TB Department:
• Diana Elizabeth Weil, Malgosia Grzemska, Mukund Waman Uplekar
and group for developing a New TB control Strategy post 2015
• Christian Lienhardt and GROUP in development of the “An
International Roadmap for Tuberculosis Research” and “Priorities
in Operational Research to Improve Tuberculosis Care and Control”
• WHO/WPRO: Catharina Van Weezenbeek
• NTP Viet Nam: Dinh Ngoc Sy and staff
• WHO/Stop TB Department:
• Diana Elizabeth Weil, Malgosia Grzemska, Mukund Waman Uplekar
and group for developing a New TB control Strategy post 2015
• Christian Lienhardt and GROUP in development of the “An
International Roadmap for Tuberculosis Research” and “Priorities
in Operational Research to Improve Tuberculosis Care and Control”
• WHO/WPRO: Catharina Van Weezenbeek
• NTP Viet Nam: Dinh Ngoc Sy and staff

25. Together
for a World free of TB !
THANKS YOU
FOR YOUR ATTENTION
vietnhung@yahoo.com