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Economic urgency and the pathway to eliminate TB

Photo: Riccardo Venturi. Economic urgency and the pathway to eliminate TB. Dr Mario Raviglione Director, Global TB Programme World Health Organization, Geneva, Switzerland. Overview. Quick overview of global burden of TB Impact of interventions and progress

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Economic urgency and the pathway to eliminate TB

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  1. Photo: Riccardo Venturi Economic urgency and the pathway to eliminate TB Dr Mario Raviglione Director, Global TB Programme World Health Organization, Geneva, Switzerland

  2. Overview • Quick overview of global burden of TB • Impact of interventions and progress • Is elimination possible in our lifetime? • What is needed to accelerate incidence decline? • What can be done today?

  3. Overview • Quick overview of global burden of TB • Impact of interventions and progress • Is elimination possible in our lifetime? • What is needed to accelerate incidence decline? • What can be done today? GLOBAL TB PROGRAMME

  4. The Global Burden of TB -2012 Estimated number of cases Estimated number of deaths • 8.6 (8.3-9.0) million • 0.5 m in children • 2.9 m in women 1.3 (1.0-1.6) million* • 74.000 in children • 410.000 in women All forms of TB 1.1 (1.0-1.2) million (13%) 320,000 (300k-340k) HIV-associated TB 170,000 (102k-242k) Multidrug-resistant TB 450.000 (300k-600k) * Including deaths attributed to HIV/TB Source: WHO Global Tuberculosis Report 2013

  5. Overview • Quick overview of global burden of TB • Impact of interventions and progress • Is elimination possible in our lifetime? • What is needed to accelerate incidence decline? • What can be done today?

  6. Global Progress on impact - 2012 • 2015 MDG on track and reduction in TB mortality of 45% since 1990 • 56 million patients cured, 1995-2012 • 22 million lives saved since 1995 • BUT, TB incidence declining too slowly, 1/3 of cases not in the system, MDR-TB challenge not yet properly addressed Ref: Global TB Control Report 2013

  7. Overview • Quick overview of global burden of TB • Impact of interventions and progress • Is elimination possible in our lifetime? • What is needed to accelerate incidence decline? • What can be done today?

  8. Full implementation of Global Plan: 2015 MDG target reached but TB not eliminated by 2050 Current rate of decline -2%/yr China, Cambodia-4%/yr W Europe after WWII -10%/yr Elimination target:<1 / million / yr-20%/yr

  9. Overview • Quick overview of global burden of TB • Impact of interventions and progress • Is elimination possible in our lifetime? • What is needed to accelerate incidence decline? • What can be done today?

  10. What is needed to accelerate incidence decline and target "elimination"? • Economic development: better nutrition & housing • Universal health coverage & social protection • TB care widely accessible to all and of high-standards • Focused, high-intensity interventions, including BCG in children • 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: In turn, this requires…new tools and increased financing (i) transmission rate, and (ii) reactivation of latent infection among the already infected

  11. What is in the pipelines for new diagnostics, drugs and vaccines in 2013? • Diagnostics: • 7 new diagnostics or diagnostic methods endorsed by WHO since 2007; • 6 in development; • yet no PoC test envisaged • Drugs: • 1 new drug approved in late 2012, but probably little impact on epidemiology; • 1 expected to be approved in 2013; • 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 just reported with no detectable efficacy

  12. Pipeline promising, but what do we need to eliminate TB? Potential impact of new tools on TB incidence in S-E Asia To eliminate TB: Very short potent regimen for all forms, and Simple regimen for mass chemoprophylaxis Synergy of interventions ! Action on both transmission and reactivation pathways Source: L. Abu Raddad et al, PNAS 2009 • 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 • Led & NAAT at microscopy lab level • Dipstick at point of care Or: Mass pre- and post-exposure vaccine Add. Effects = effects also on latency and infectiousness of cases in vaccinated

  13. Tools required for eradication in our lifetime (drugs): Do we have potent regimen for treatment and prevention? • Ideally, we needas short a regimenas possible active against all types of TB, transforming TB into a common infectious disease. However, we only have “short-course chemotherapy” • Ideally, we need mass chemoprophylaxis (TLTBI), as TLTBI prevents reactivation with up to 70% efficacy. However: • Safety issue on a mass scale: fatal hepatitis • 4.13 (95% CI 0.5-34) Risk Ratio (vs placebo) (Cochrane Review, 2010); • 4-7/100,000 incidence (Millard PS et al. West J Med. 1996;164:486-91.) • Single dose treatment not available: no existing drug kills intracellular bacteria (such as M. tuberculosis) in a non-replicative state • Screening of truly infected or at real risk not available: no “IGRA-plus”

  14. Reality check about treatment and chemoprophylaxis • Today we do not have a potent treatment regimenthat lasts <2 months and treats TB and M/XDR-TB. It will probably not be available for at least 5-10 years • Today we do 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 • Today we do not have a testcapable of identifying who will progress to active TB among the ?2 billion infected

  15. BCG evidence and MVA85A phase 2b trial results • BCG: efficacy in disseminated pediatric forms proven. Efficacy against adult contagious forms variable. Revaccination efficacy nihil or dubious • MVA85A: • Safe • Showing it is feasible to test vaccine candidates in large trials, but…No detectable efficacy

  16. Global TB Vaccine Pipeline 2013: good but needs to keep growing Phase I Phase II Phase IIb Phase III Reality check about vaccines • Today we do not have a potent pre- and post-exposure vaccine, we have BCG • Today we do not have yet clarity about correlates of immunity and bio-markers • Today, we do not fully understand pathogenesis and immunity VPM 1002Max Planck, VPM, TBVI MVA85A/AERAS-485OETC, Aeras Ad5 Ag85A McMaster CanSino Hybrid-I + IC31SSI, TBVI, EDCTP, Intercell AERAS-402/ Crucell Ad35Crucell, Aeras ID93 + GLA-SE IDRI, Aeras RUTIArchivel Farma, S.L M72 + AS01GSK, Aeras Hyvac 4/ AERAS-404 + IC31SSI, sanofi-pasteur, Aeras, Intercell M. Vaccae Anhui Longcom, China Viral vector H56 + IC31SSI, Aeras, Intercell MTBVAC TBVI, Zaragoza, Biofabri rBCG Immunotherapeutic: Mycobacterial – whole cell or extract Protein/adjuvant Hybrid-I +CAF01 SSI, TBVI Attenuated M.tb 16 16

  17. Overview • Quick overview of global burden of TB • Impact of interventions and progress • Is elimination possible in our lifetime? • What is needed to accelerate incidence decline? • What can be done today?

  18. What can be done? • Enhance strategy and approach to TB care, control and research • Mobilize resources for research

  19. DRAFT Post-2015 TB Strategy at a glance VISION: • A WORLD FREE OF TB • Zero deaths, disease and suffering due to TB GOAL: • End the Global TB Epidemic TARGETS FOR 2035: • 95% reduction in TB deaths (compared with 2015) • 90% reduction in TB incidence rate (<10/100,000) MILESTONES FOR 2025: • 75% reduction in TB deaths (compared with 2015) • 50% reduction in TB incidence rate (< than 55/100,000) • No affected families face catastrophic costs due to TB

  20. Projected acceleration of TB incidence decline to target levels Current global trend: -2%/year Average -10%/year Optimize current tools, pursue universal health coverage and social protection Introduce new vaccine, new prophylaxis -5%/year Average -17%/year

  21. Post-2015 Global TB Strategy Proposed Pillars and Principles Bold policies and supportive systems Integrated, patient-centered TB care and prevention Intensified research and innovation Protecting and promoting human rights, ethics and equity Government stewardship and accountability, with monitoring and evaluation Adaptation of the strategy and targets at country level, with global collaboration Building a strong coalition with civil society and communities

  22. Post-2015 Global TB Strategy Proposed Pillars Targets: 95% reduction in deaths and 90% reduction in incidence (< 10 cases / 100,000 population) by 2035

  23. This is what is necessary: Vaccine blueprint – but do we have enough funding for it? • Five keys to progress: • Creativity in research and discovery • Correlates of immunity and biomarkers for TB vaccines • Clinical trials: harmonization & cooperation • Rational selection of TB vaccine candidates • The critical need for advocacy, community acceptance and funding

  24. Investments in TB R&D by Research Category: 2005-2011. For vaccines: no increase $225,000,000 $150,000,000 $75,000,000 Infrastructure/Unspecified Drugs Basic Science Vaccines Diagnostics Operational Research $0 2005 $114,862,738 $81,892,167 $68,351,530 $40,741,527 $19,408,124 $32,170,084 2006 $144,336,532 $91,643,009 $76,555,111 $43,205,600 $31,890,329 $30,194,127 2007 $170,233,497 $113,325,202 $73,225,383 $40,734,199 $42,435,113 $33,967,288 2008 $174,178,052 $98,728,019 $109,337,224 $25,032,930 $49,788,950 $34,411,742 2009 $191,483,304 $172,447,841 $110,133,485 $56,686,918 $38,921,229 $49,536,760 2010 $230,540,443 $129,008,413 $78,446,298 $83,145,063 $48,410,889 $60,895,355 2011 $250,038,877 $120,361,419 $95,446,326 $44,617,845 $55,043,541 $84,140,175

  25. Conclusions and call to action • The world is on track to achieve the (un-ambitious) 2015 target of incidence reduction, and current measures can reduce deaths and cure patients, but theycannot eliminate TB • 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) intensified research efforts • For eliminationone would need potent short treatments, mass TLTBI and potent pre- and post-exposure vaccines. None is available today • Basic researchis fundamental to gain further knowledge and R&D pipelines must be expanded , nurtured and well-financed. • Increased financial resources for TB Vaccine development: we need a new global TB vaccine “partnership” of all engaged developers, investors, donors so that efforts are synergised and synchronised. This is not a job for one agency only!

  26. Eradication of tuberculosis: Will it be feasible? I bet you: a potent vaccine will do! …Merci beaucoup!

  27. Tools required for eradication in our lifetime: (1a) A potent regimen for treatment • Assessment of fluoroquinolone trials in early 2014 • Three trials: • OFLOTUB/Gatifloxacin for TB Phase III trial: gatifloxacin substituted for ethambutol – 4 months Rx - results expected second half 2013 • ReMox: moxifloxacin substituted for ethambutol or isoniazid – 4 months Rx - results expected early 2014 • Rifaquin trial: moxifloxacin substituted for ethambutol (intensive phase), associated with rifapentine once weekly in continuation phase – presentation at CROI 2013. 4-month arm did not work • NC-001 regimen: PA-824, pyrazinamide, moxifloxacin

  28. Tools required for eradication in our lifetime: a potent regimen for prevention/ treatment of latent infection? • IPT prevents TB with around 70% efficacy, individual benefits clear, population level less clear (40% reported). • WHO recommends treatment of LTBI for: • People living with HIV (PLHIV) • Children <5 contacts of a TB case • Recent TST converters • Isoniazid 5 mg/kg daily (max 300 mg) for at least 6 months, but shorter regimens also efficacious (12wHP, 3HR) • Fatal hepatitis: 2010 Cochrane review 4.3 RR (0.5-34); incidence 4-7/100,000 (Millard 1996) • Modelling shows potential, but feasibility and scale-up remain an issue. No predictive test

  29. Tools required for eradication in our lifetime (2: Vaccines): Perspectives for a potent vaccine Mass vaccination with a potent vaccine: • pre-exposure: • post-exposure: would prevent infection to occur, and therefore disease, but impact would take a long time to appear would prevent “reactivation”, and would have impact on transmission as new cases will not emerge any longer out of the pool of already infected. However, it would not prevent new infection

  30. Enhanced TB Strategy Post-2015 (draft) Targets: 95% reduction of deaths and < 10 cases / 100,000 population by 2035

  31. Annual Global Plan Research Funding Targets vs. 2011 Investments: for vaccines, ¼ available $800,000,000 $740,000,000 $600,000,000 $400,000,000 $420,000,000 $380,000,000 $340,000,000 $250,038,877 $200,000,000 $80,000,000 $120,361,419 $95,446,326 $84,140,175 $55,043,541 $0 Fundamental research New diagnostics New drugs New vaccines Operationalresearch Global Plan Annual Targets 2011 Investments

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