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Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director, Global TB Programme World Health Organization, Geneva, Switzerland Photo: Riccardo Venturi 23 rd Swiss Symposium on TB 20 March 2014 Münchenwiler, Suisse
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Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

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Page 1: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Achievements during the last 20 years and perspectives for elimination

Dr Mario Raviglione Director, Global TB Programme

World Health Organization, Geneva, Switzerland

Photo: Riccardo Venturi

23rd Swiss Symposium on TB 20 March 2014

Münchenwiler, Suisse

Page 2: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Overview

Overview of global burden of TB

Impact of interventions and progress

What future for TB control: is elimination possible in our lifetime?

Status of the R&D pipelines

What’s next?

Page 3: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Overview

Overview of global burden of TB

Impact of interventions and progress

What future for TB control: is elimination possible in our lifetime?

Status of the R&D pipelines

What’s next?

Page 4: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Estimated number of cases

Estimated number of deaths

1.3 (1.0-1.6) million* •74.000 in children •410.000 in women

8.6 (8.3-9.0) million • 0.5 m in children • 2.9 m in women

450.000 (300k-600k)

All forms of TB

Multidrug-resistant TB

HIV-associated TB 1.1 (1.0-1.2) million (13%)

320,000 (300k-340k)

Source: WHO Global Tuberculosis Report 2013 * Including deaths attributed to HIV/TB

The Global Burden of TB -2012

170,000 (102k-242k)

Page 5: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

South-East Asia 39%

Western Pacific 19%

Africa 27%

E. Mediterranean 8%

Europe 4%

Americas 3%

38% in India + China 26% in India

GLOBAL TB PROGRAMME

Ref: Global TB Control Report 2013

Estimated TB incidence rate, 2012

Page 6: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Percentage of new TB cases with MDR-TB Globally 3.6% (95% CI: 2.1–5.1%)

GLOBAL TB PROGRAMME

Ref: Global TB Control Report 2013

Page 7: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

2012: Estimated number of MDR-TB cases out of notified TB cases - 80% of all cases are in 12 countries

Russian Fed.: 46,000 (15%)

India: 64,000 (21%)

China: 59,000 (20%)

Philippines: 13,000

Pakistan: 11,000

South Africa: 8,100

Ukraine: 6,800

Indonesia: 6,900

Kazakhstan: 8,800

Bangladesh: 4,200 Myanmar: 6,000

Uzbekistan: 4,000

Page 8: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

92 countries notified at least one case of XDR-TB

GLOBAL TB PROGRAMME

Ref: Global TB Control Report 2013

Page 9: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Overview

Overview of global burden of TB

Impact of interventions and progress

What future for TB control: is elimination possible in our lifetime?

Status of the R&D pipelines

What’s next?

Page 10: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

The global response: Targets, Global Plan, and Stop TB Strategy

1. Pursue high-quality DOTS expansion

2. Address TB-HIV, MDR-TB, and needs of the poor and vulnerable

3. Contribute to health system strengthening

4. Engage all care providers

5. Empower people with TB and communities

6. Enable and promote research

Goal 6: to have halted by 2015 and begun to reverse the incidence…

2015: 50% reduction in TB prevalence and deaths compared to 1990

2050: elimination (<1 case per million population)

Page 11: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

TB cases and deaths, 1990–2012: achievements of control efforts with available tools (absolute numbers)

Mortality

Total mortality peaked early 2000s at 1.8 million 1.3 million in 2012

5

Incidence peaked at 9 million in early 2000s 8.6 million in 2012

Incidence

Ref: Global TB Control Report 2013

Page 12: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

8.6

5.7

Global notifications Estimated incidence

The case detection/notification gap, 2012

Nearly 3 million TB cases either not notified or not

detected

NO elimination without “capturing” them

2.9 million missed

Ref: Global TB Control Report 2013

Page 13: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Global Progress on impact - 2012

TARGETS ON TRACK Incidence falling slowly: 2015 MDG on track

Reduction in TB mortality of 45% since 1990 22 million lives saved since 1995

87% cure rate and 56 million patients cured, 1995-2012

Ref: Global TB Control Report 2013

5 PRIORITIES FOR ACTION Reaching the “missed” cases (3 million not in the system)

Address MDR-TB as crisis

Accelerate response to TB/HIV

Increase financing to close resource gaps Ensure rapid uptake of innovations

Page 14: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Overview

Overview of global burden of TB

Impact of interventions and progress

What future for TB control: is elimination possible in our lifetime?

Status of the R&D pipelines

What’s next?

Page 15: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

With current incidence decline: 2015 MDG target reached but TB not eliminated by 2050

Current rate of decline -2%/yr

W Europe after WWII: -10%/yr

China, Cambodia: -4%/yr

Elimination target:<1 / million / yr -20%/yr

US and Canada Eskimos, 1950s-60s: -17%/yr

Page 16: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Economic development: better nutrition & housing Universal health coverage & social protection TB care widely accessible to all and of high-standards Focused, high-intensity interventions Screening of high-risk groups and mass TLTBI Infection control practices

However… while incidence decline can accelerate, “elimination” is

another story, as it requires major reduction of:

This translates into…new tools and increased financing

(i) transmission rate, and (ii) reactivation of latent infection among the already infected

What is needed to accelerate incidence decline and target "elimination"?

Page 17: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Overview

Overview of global burden of TB

Impact of interventions and progress

What future for TB control: is elimination possible in our lifetime?

Status of the R&D pipelines

What’s next?

Page 18: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

What is in the pipelines for new diagnostics, drugs and vaccines in 2014?

Diagnostics: ₋7 new diagnostics or diagnostic methods endorsed by WHO since 2007; ₋6 in development; Drugs: -2 new drugs approved in 2012 & 2013 for MDR-TB; -a regimen and other 2-3 drugs likely to be introduced in the next 4-7 years Vaccines: ₋11 vaccines in advanced phases of ₋development; ₋1 reported in 2013 with no detectable efficacy

Page 19: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Pipeline promising, but what do we need to eliminate TB? Potential impact of new tools on TB incidence in S-E Asia

Sou

rce:

L. A

bu R

adda

d et

al,

PN

AS 2

009

Add. Effects = effects also on latency and infectiousness of cases in vaccinated

•Led & NAAT at microscopy lab level •Dipstick at point of care

•Regimen 1 = 4-month, no effect on DR •Regimen 2 = 2-month, 90% effective in M/XDR •Regimen 3 = 10-day, 90% effective in M/XDR

To eliminate TB: 1.Very short potent regimen for all forms 2.Simple regimen for mass chemoprophylaxis 3.Not a single drug or two…

Or: Mass pre- and post-exposure vaccine

Synergy of interventions ! Action on both transmission and reactivation pathways

Page 20: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Time-to-result: 1 h 45 min

GeneXpert

DNA molecules are mixed with dry PCR reagents

Sample is automatically filtered & washed

Ultrasonic lysis of filter-captured organisms to release DNA

Semi-nested real-time amplification & detection in

integrated reaction tube

4

5

6

Concentrates bacilli & removes inhibitors

1

2

Sputum liquefaction & inactivation with 2:1 SR

Transfer of 2 ml after 15 min

3 End of hands on work

Printable test result

A new test: Xpert MTB/RIF

Page 21: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Xpert: updated WHO Recommendations, 2013

1. Xpert MTB/RIF should be used as the initial diagnostic test in individuals suspected of having MDR-TB or HIV-associated TB. (Strong recommendation)

2. Xpert MTB/RIF may be considered as a follow-on test to microscopy in settings where MDR-TB or HIV is of lesser concern, especially in further testing of smear-negative specimens. (Conditional recommendation acknowledging major resource implications)

3. Xpert MTB/RIF use also expanded to for use in childhood TB and extrapulmonary TB

Vorführender
Präsentationsnotizen
WHO policy on Xpert MTB/RIF has 2 main recommendations.
Page 22: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,
Page 23: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

New drugs: Bedaquiline (BDQ) – a diarylquinoline First drug develooped for TB in forty years

Only data from Phase IIb trials available , further efficacy and safety data needed from rigorously conducted Phase III trials

On December 28, 2012, the U.S. FDA approved BDQ

In early 2013, WHO commissioned independent review of data, assessment of validity of surrogate markers for MDR-TB outcome, and cost-effectiveness study

In January 2013, WHO held an Expert Committee meeting to get advice

In June 2013, after STAG-TB endorsement and through publication of interim guidelines, WHO recommended BDQ use for MDR-TB under five strict conditions

WHO has disseminated its guidelines to all Member States and is working on operational manual and other guidance

Page 24: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Bedaquiline: Interim WHO policy guidance

BDQ may be added to a WHO-recommended regimen in adult patients with pulmonary MDR-TB, under five specific conditions (conditional recommendation, very low confidence in estimates of effect): 1. Treatment under close monitoring (eg, sound protocols) 2. Proper patient selection (caution: PLHIV and >65; no: children & pregnancy) 3. Patient informed consent required 4. Treatment design based on WHO recommendations (eg, DST, dose, never adding a single drug to a failing regimen) 5. Active pharmacovigilance (esp. cardiac, liver and renal toxicities) Urgent WHO call: acceleration of phase III trial; accurate DST; prospective collection of operational data on BDQ implementation

Page 25: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

New drugs: Delamanid – a nitroimidazole European Medicines Agency authorized on 21-11-2013

Page 26: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

1. Today we have two new drugs for MDR-TB, but we do not have a potent treatment regimen that lasts <2 months and treats TB and M/XDR-TB. It will probably not be available for at least 5-10 years

2. Today we have a treatment for latent TB infection that is 70% efficacious, but difficult to scale-up to whole population (? 2 billion infected) or even to high-risk groups

3. Today we do not have a test capable of identifying who will progress to active TB among the ?2 billion infected

Reality check about treatment and chemoprophylaxis

Page 27: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

BCG evidence and MVA85A phase 2b trial results

Safe Showing it is feasible to test vaccine candidates in large trials, but…

No detectable efficacy

• BCG: efficacy in disseminated pediatric forms proven. Efficacy against adult contagious forms variable. Revaccination efficacy dubious

• MVA85A:

Page 28: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

28 28

Ad5 Ag85A McMaster CanSino

VPM 1002 Max Planck, VPM,

TBVI

Hybrid-I + IC31 SSI, TBVI, EDCTP,

Intercell

Phase II Phase III Phase IIb

Immunotherapeutic: Mycobacterial – whole cell

or extract

ID93 + GLA-SE IDRI, Aeras

Hyvac 4/ AERAS-404 + IC31

SSI, sanofi-pasteur, Aeras, Intercell

H56 + IC31 SSI, Aeras, Intercell

MVA85A/AERAS-485

OETC, Aeras

AERAS-402/ Crucell Ad35 Crucell, Aeras

RUTI Archivel Farma, S.L

M. Vaccae Anhui Longcom,

China

M72 + AS01 GSK, Aeras

MTBVAC TBVI, Zaragoza,

Biofabri

rBCG

Viral vector

Protein/adjuvant

Attenuated M.tb

Hybrid-I + CAF01 SSI, TBVI

Global TB Vaccine Pipeline 2014: good but needs to keep growing

Reality check about vaccines 1.Today we do not have a potent pre- and post-exposure vaccine, we have BCG

2.Today we do not have yet clarity about correlates of immunity and bio-markers

3.Today, we do not fully understand pathogenesis and immunity

Page 29: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Assessment of new tools – 2014 Good pipelines, but no revolution yet

Diagnostics: ₋7 new diagnostics or diagnostic methods endorsed by WHO since 2007; ₋6 in development;

₋yet no PoC test Drugs: -2 new drugs approved in 2012 & 2013 for MDR-TB : little impact on epidemiology; -a regimen and other 2-3 drugs likely to be introduced in the next 4-7 years

-Yet no new regimen for all forms Vaccines: ₋11 vaccines in advanced phases of ₋development; ₋1 reported in 2013 with no detectable efficacy

₋Yet no new vaccine

Page 30: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Overview

Overview of global burden of TB

Impact of interventions and progress

What future for TB control: is elimination possible in our lifetime?

Status of the R&D pipelines

What’s next?

Page 31: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,
Page 32: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Vision, goal and targets

A WORLD FREE OF TB Zero deaths, disease and suffering due to TB

End the Global TB Epidemic

95% reduction in TB deaths (compared with 2015) 90% reduction in TB incidence rate (<10/100,000) No affected families face catastrophic costs due to TB

75% reduction in TB deaths (compared with 2015) 50% reduction in TB incidence rate (compared with 2015) (< than 55/100,000) No affected families face catastrophic costs due to TB

VISION:

GOAL:

TARGETS FOR 2035:

MILESTONES FOR 2025:

Page 33: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Projected acceleration of TB incidence decline to target levels

Optimize current tools, pursue universal health

coverage and social protection

Introduce new vaccine,

new prophylaxis

Average -10%/year

-5%/year

Current global trend: -2%/year

Average -17%/year

Vorführender
Präsentationsnotizen
The 10% per year fall in incidence that is needed by 2025 has been previously achieved only within the wider context of UHC and broader social and economic development. UHC means providing all people with access to needed services of sufficient quality to be effective, without their use imposing financial hardship. Progress in the countries with the highest burden today, such as China, India, Indonesia, Nigeria and South Africa will strongly influence whether targets can be achieved or not. To lower cases to 10 per 100,0000 population by 2035 ("end the global TB epidemic") and achieve a 95% reduction in TB deaths by 2035 will need a technological breakthrough by 2025 that will allow an unprecedented acceleration in the rate at which TB incidence falls between 2025 and 2035. This will only happen with substantial investment in R&D in the years up to 2025, so that new tools such as a post-exposure vaccine or a short, efficacious and safe treatment for latent infection that could substantially lower the risk of developing TB among the approximately 2 billion people that are already infected, are developed.
Page 34: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

Integrated, patient-centered TB Care and

Prevention

Early diagnosis of TB including universal drug-susceptibility testing ; systematic screening of contacts and high-risk groups

Treatment of all people with TB including drug -resistant TB; and patient support

Collaborative TB/HIV activities and management of co-morbidities

Preventive treatment for persons at high-risk; and vaccination against tuberculosis

Bold policies and supportive systems

Political commitment with adequate resources for TB care and prevention

Engagement of communities , civil society organizations, and all public and private care providers

Universal health coverage policy; and regulatory framework for case notification, vital registration, quality and rational use of medicines, and infection control

Social protection, poverty alleviation, and actions on other determinants of TB

Intensified Research and Innovation

Discovery, development and rapid uptake of new tools, interventions and strategies

Research to optimize implementation and impact, and promote innovations

Targets: 95% reduction in deaths and 90% reduction in incidence (< 10 cases / 100,000 population) by 2035

Post-2015 Global TB Strategy Proposed Pillars

Page 35: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

1. The world is on track to achieve the 2015 target of incidence reduction, and current measures can reduce deaths and cure patients, but they cannot eliminate TB

2. For elimination one would need potent short treatments, mass TLTBI, and potent pre- and post-exposure vaccines. None is available today . Basic research is fundamental to gain further knowledge and fill the R&D pipelines

3. MDR-TB challenge: a real public health crisis in some countries. Urgent measures needed: increase access to care, ensure rapid diagnosis, procure and ensure second-line medicines, support patients, continue R&D. Above all: prevent MDR-TB!

4. Three pillars will be the basis to accelerate incidence decline: (i) universal access to quality TB care and control, (ii) bold health system policies, and (iii) much intensified research efforts

Conclusions

Page 36: Photo: Riccardo Venturi Achievements during the last 20 years … · 2014-03-24 · Achievements during the last 20 years and perspectives for elimination Dr Mario Raviglione Director,

…grazie, merci, danke, thank you