Tuberculosis 2013: basics, burden, impact, challenges, innovations Photo: Riccardo Venturi GLOBAL TB PROGRAMME Dr Mario Raviglione Director, Global TB Programme, World Health Organization, Geneva, Switzerland Geneva Journalism & Health Mentoring Initiative Geneva, 20 May 2013

GLOBAL TB PROGRAMME Overview Basics Burden of TB, TB/HIV, MDR-TB Impact of interventions, and progress in TB care and control Vision beyond 2015 Innovations necessary towards elimination

GLOBAL TB PROGRAMME Tuberculosis (TB) is one of the oldest diseases of humans TB is a major cause of death worldwide, it competes with HIV/AIDS as the greatest killer globally due to a single infectious agent TB is also one of the top killers of women worldwide, half a million women died from TB in 2011 TB is caused by the bacterium Mycobacterium tuberculosis TB usually affects the lungs, although other organs are involved in 15-30% of cases If properly treated, TB caused by drug-susceptible strains is curable in virtually all cases If untreated, TB may be fatal within 5 years in 2/3 of cases One third of world has latent TB infection Tuberculosis: basics

GLOBAL TB PROGRAMME Mycobacterium tuberculosis complex: M. tuberculosis, M. bovis, M. microti, M. africanum, M. pinnipedii, M. caprae ( and M. canettii) Robert Koch discovered the cause of TB 24 March 1882

GLOBAL TB PROGRAMME How is TB transmitted?..Via aerosolised particles from infectious patients

TB linked to HIV infection, malnutrition, alcohol, drug and tobacco use, diabetes Half a million women and over 65,000 children die of TB each year; 10 million “TB” orphans Migrants, prisoners, minorities, refugees face risks, discrimination & barriers to care Poor, crowded & poorly ventilated settings Who carries the burden of tuberculosis? …mostly, the most vulnerable

GLOBAL TB PROGRAMME Estimated number of cases Estimated number of deaths 1.4 million* (1.3–1.6 million) 8.7 million (8.3–9.0 million) Up to 0.5 million All forms of TB Multidrug-resistant TB HIV-associated TB 1.1 million (13%) (1.0–1.2 million) 430,000 (400,000–460,000) Source: WHO Global Tuberculosis Report 2012 * Including deaths attributed to HIV/TB The Global Burden of TB Unknown, but probably > 150,000

GLOBAL TB PROGRAMME Incidence rates, 2011 Highest rates in Africa, linked to high rates of HIV infection ~80% of HIV+ TB cases in Africa Per population ≥ –299 50–149 0–24 25–49

GLOBAL TB PROGRAMME TB/HIV co-infection: 80% of burden in Africa TB leading cause of death in PLHIV ¼ of PLHIV worldwide die due to TB. PLHIV infected with TB times more likely to develop active TB. Untreated, TB in PLHIV leads to death in weeks 80% of all TB/HIV cases are in Africa

GLOBAL TB PROGRAMME Drug resistant TB: Major challenge o Multi-drug resistant TB (MDR-TB) Second-line drugs, toxic, costly, lengthy o Extensively drug resistant TB (XDR-TB) Almost incurable, fatal o Drug resistant TB results from inadequate TB care and irrational use of drugs o New York epidemic in early 90’s – Cost of response: US$ 1 billion

GLOBAL TB PROGRAMME The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.  WHO All rights reserved Estimated number of MDR-TB Cases, 2011 >60% of all cases are in 6 countries Russian Federation 44,000 (14% of global MDR burden) India 66,000 (21% of global MDR burden) China 61,000 (20% of global MDR burden) Philippines 11,000 (4% of global MDR burden) Pakistan 10,000 (3% of global MDR burden) South Africa 8,100 Based on old survey data

GLOBAL TB PROGRAMME Spotlight on XDR-TB Case of Atlanta lawyer with presumed XDR-TB caused international concern

GLOBAL TB PROGRAMME To date, 84 countries have reported at least one XDR-TB case About 9% of MDR-TB cases are XDR

GLOBAL TB PROGRAMME The case of Mumbai and the “TDR-TB outbreak” Udwadia ZF, Amale RA, Ajbani KK, Rodrigues C. Totally drug-resistant tuberculosis in India. Clin Infect Dis Feb 15;54(4):579–81.

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 : elimination (<1 case per million population)

Pursue DOTS Address TB/HIV and MDR-TB Strengthen systems Engage all care providers Empower communities Promote research

GLOBAL TB PROGRAMME Incidence Mortality Global Progress 51 million patients cured, million lives saved since MDG and other international targets on track BUT, TB incidence declining far too slowly, 1/3 of cases not in the system, MDR-TB un-tackled etc.

GLOBAL TB PROGRAMME Innovating with GeneXpert WHO endorsement December 2010 Nearly 83 countries using it in March 2013

GLOBAL TB PROGRAMME WHO GLOBAL TB PROGRAMME The WHO Global TB Programme aims to advance universal access to TB prevention, care and control, guide the global response to threats, and promote innovation. A World FREE of TB VISION: MISSION:

GLOBAL TB PROGRAMME What we do: our core functions Provide global leadership on TB; Develop policies, strategies and standards for TB prevention, care and control; Coordinate technical support to Member States, catalyze change, and build sustainable capacity; Monitor the global TB situation, and measure progress in TB care, control, and financing; Shape the TB research agenda and stimulate the generation, translation and dissemination of valuable knowledge; Facilitate and engage in partnerships for TB action.

ZERO TB DEATHS VISION A WORLD FREE OF TB The TB Elimination Strategy ZERO TB CASES ZERO TB SUFFERING TOWARDS

Universal high- quality TB care and prevention Bold policies and supportive systems Intensified research and innovation Proposed Pillars and Principles of the Post-2015 TB Strategy

Targets for 2025/2030 Target 1 75%/80% reduction in deaths due to TB (compared with 2015) Target 2 40%/60% reduction in TB incidence rate (compared with 2015) Target 3 No catastrophic expenditures for families affected by TB

GLOBAL TB PROGRAMME CHALLENGES TO “ELIMINATION"? 1.Funding not secure; catastrophic expenditure for the poor 2.Only 2/3 of estimated cases reported or detected (late) 3.TB/HIV major impact in Africa 4.MDR-TB, with high burden in former USSR and China 5.Un-engaged non-state practitioners and communities, and the private sector 6.Weak health policies, systems and services 7.Social and economic determinants maintain TB 8.Research awakening: old diagnostics, drugs and vaccines

GLOBAL TB PROGRAMME ROADBLOCK 1: Lack of commitment "… …"

GLOBAL TB PROGRAMME ROADBLOCK 2: Funding US$ billions Funding gap vs Global Plan ~ US$2–3 billion per year Funding gaps reported by countries US$0.7 billion in 2013

GLOBAL TB PROGRAMME Sputum smear microscopy Discovered 1882 DIAGNOSTIC 1st-line TB drugs Discovered TREATMENTVACCINE BCG Developed 1920s ROADBLOCK 3: Today, most used tools for TB control are old and not conducive to elimination

GLOBAL TB PROGRAMME ROADBLOCK 3: Bedaquiline – First drug in forty years Only data from Phase IIb trials available, further efficacy and safety data will be needed from rigorously conducted Phase III trials On December 28, 2012, the U.S. Food and Drug Administration approved bedaquiline Caution on use WHO advises that a single drug deemed to be effective should never be added alone to a regimen to which a patient is not responding to WHO has initiated a review process aimed at developing rapid interim guidance on the potential use of bedaquiline for the treatment of MDR-TB. Interim guidance from WHO in coming month

GLOBAL TB PROGRAMME 1.For elimination one would need potent short treatments, mass TLTBI and potent pre- and post-exposure vaccines. None is available today 2.Basic research is fundamental to gain further knowledge and R&D pipelines must be expanded, nurtured and well-financed. 3.TB Vaccine development: we need a global coalition of all engaged agencies so that efforts are harmonised and coordinated. This is not a job for one agency only! 4.Increased financial resources for research: keep working together to provide the right messages to investors ROADBLOCK 3: Research key for elimination

GLOBAL TB PROGRAMME 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

GLOBAL TB PROGRAMME Roadblock 4: Unregulated private sector Private sector is first point of care in many settings Diverse network of formal and informal providers ranging from hospitals, corporate sector to the traditional healers and quacks Contribution to finding people with TB between 10%-40% in countries Collaboration exists but still not enough in many settings. Efforts need to be made on both ends Untapped potential Private sector engagement crucial in closing the gap on case detection

GLOBAL TB PROGRAMME Roadblock 5: Taking on the Pharmaceutical Industry Lobbying, promotion, economic incentives and infiltration Quality differentiation based on level of regulation Counterfeit medicines Drug resistance BUT, we need them on our side!

GLOBAL TB PROGRAMME TB crosses borders

How would you increase the profile of TB? Question for you ?