La tubercolosi nel terzo millennio Lucio Casali Firenze, 21 novembre 2015 1

The Global Burden of TB - 2013 Estimated number of cases Estimated number of deaths 1.5 million* 80.000 in children 510.000 in women 9 million 126 per 100,000 550,000 in children 3.3 m in women 480,000 All forms of TB Multidrug-resistant TB HIV-associated TB 1.1 million (13%) 360,000 210,000 Source: WHO Global TB Report 2014 * Including deaths attributed to HIV/TB

TB cases and deaths in slow decline, 1990-2013 Total mortality peaked in 2002 at 1.7 million 1.5 million in 2013 Incidence peaked at 9.5 million in 2004 9 million in 2013 All TB deaths

Accelerating response to TB/HIV means cutting suffering, transmission and mortality Estimated HIV prevalence in new TB cases, 2013 78% of TB/HIV cases in Africa Ref: Global TB Control Report 2014 Other co-morbidities emerging in other regions Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

Addressing MDR-TB as a crisis The “orphan” disease Percentage of new TB cases with MDR-TB Ref: Global TB Control Report 2014 Highest % in the former USSR countries India, China, Russia, Pakistan and Ukraine have 60% of all MDR-TB cases Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

…mostly, the most vulnerable Who carries the burden of tuberculosis? …mostly, the most vulnerable TB spreads in poor, crowded & poorly ventilated settings 510,000 women and 80,000 children die of TB each year; 10 million “TB” orphans Migrants, prisoners, minorities, refugees face risks, discrimination & barriers to care TB linked to HIV infection, malnutrition, alcohol, drug and tobacco use, diabetes

Poverty-disease trap as applied to TB Health in all policies, UHC, public health TB diagnosis and treatment Wealth and wealth distribution Undernutrition Poor housing Risk factors for infectious diseases and NCDs Poor health care access TB Poverty Social and financial support Worse health and stigma – loss of income Catastrophic health expenditure: 10-50% of annual income lost!

Patient Total Health C.S.

Conclusion This review suggests that there is an unacceptable time delay before the diagnosis of pulmonary tuberculosis is made. There is a need to revise the current case finding strategies.

Global progress on impact - 2013 37 million lives saved since 2000 Reduction in TB mortality rate 45% since 1990 Incidence falling slowly (1.5%/yr): 2015 MDG on track 4.8 million lives saved since 2005 through TB/HIV collaborative activities 86% cure rate 61 million patients cured, 1995-2013

Challenges: Priorities for action 2015 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 Intensify research and ensure rapid uptake of innovations

Share of total missed cases India: 1 million cases “missed” Reaching the "missed" cases early means cutting transmission (nearly 3 million not diagnosed or reported) Share of total missed cases 9 million estimated 6 million notified 10 countries account for 74% (2.4 million) of the estimated “missed” cases globally India: 1 million cases “missed” Estimated incidence Global notifications Ref: Global TB Control Report 2013

Vision, goal, targets, milestones Vision: A world free of TB Zero TB deaths, Zero TB disease, and Zero TB suffering Goal: End the Global TB epidemic (<10 cases per 100,000 population)   INDICATORS MILESTONES TARGETS 2020 2025 SDG 2030 End TB 2035 Reduction in number of TB deaths compared with 2015 (%) 35% 75% 90% 95% Reduction in TB incidence rate compared with 2015 (%) 20% (<85/100 000) 50% (<55/100 000) 80% (<20/100 000) 90% (<10/100 000) TB-affected families facing catastrophic costs due to TB (%) Zero

The End TB Strategy: 3 pillars and 4 Principles Bold policies and supportive systems Integrated, patient-centered TB care and prevention Intensified research and innovation Government stewardship and accountability, with monitoring and evaluation Building a strong coalition with civil society and communities Protecting and promoting human rights, ethics and equity Adaptation of the strategy and targets at country level, with global collaboration

Le nuove metodiche diagnostiche La più recente novità nella diagnosi di laboratorio è il GeneXpert

Le nuove metodiche diagnostiche

Xpert MTB/RIF: performance Hot-spot gene rpoB Campioni clinici Identificazione casi di TBC Specificità 98-99% Sensibilità 97-100%, BAAR-pos. 75-84%, BAAR-neg. Identificazione casi resistenti alla rifampicina Specificità 97-99% Sensibilità 91-97% Casi di co-infezione TBC-HIV Sensibilità 86% (HIV-neg: 92%) Boehme CC et al 2011. Lancet 377(9776):1495-505 Theron G et al 2011. Am J Respir Crit Care Med 184:132-140

Political commitment needs to be backed by financing IMPLEMENTATION $2 billion Funding gap RESEARCH $677 M $1.32 billion Funding gap $8 billion funding required for TB prevention, diagnosis and treatment $2 billion funding required for research and development TAG TB R&D report 2013 Workshop for 18 high-priority countries of the WHO European Region on recording and reporting of drug resistant tuberculosis

Funding gaps, US$ billions by region Rest of the World Biggest gaps in Africa: 59% of total gap, 2014-16 19% Gap in Asia could be bigger if domestic funding (in India, Indonesia, Philippines etc.) does not grow at projected level Africa Asia 22% 59% Smaller gaps in Rest of World but critical to fill for MDR response and quality TB care, esp. in Europe Rest of World Africa Asia This slides shows the funding needs and gaps by Regions. Again there are 3 points to highlight here: CLIC: The first is that Africa accounts for the biggest share of the total gap - 59%; CLIC: The second is that Asia accounts for 22% of the gap, although, as I pointed out on the previous slide, this gap will be bigger if the domestic funding projections used for the demand forecast do not materialize in practice. For instance, we assume that some governments in large countries in Asia will keep their commitment to progressively move towards full financing from domestic sources. If this does not happen, the gap will be large, even in growing economies. The third point is that the gaps look relatively small in other parts of the world such as Eastern Europe, but I need to emphasize that it is critical to fill these gaps to respond to the MDR-TB epidemic and to ensure provision of high quality TB care, within reformed and better systems, that prevents MDR-TB from arising.

Impact if funding gap closed: lives saved Millions Millions Lives saved (TB) Lives saved (MDR-TB) 0.2 million Status Quo Status Quo This slide shows the impact in terms of lives saved if there is full funding for the period 2014-2016 compared with a status quo scenario, meaning a flat line. With full funding, an extra 1.2 million lives will be saved. In addition, if we stick with the status quo, there will be a failure in our global response to MDR-TB and a failure to adopt innovations, especially rapid diagnostic tests for TB and MDR-TB that we are strongly promoting. Can we really afford that?? Status quo implies: 1.2 million lives lost Failure in MDR response Failure to adopt rapid diagnostic tests

ACTIONS NEEDED ON ALL FRONTS FROM PREVENTION TO CURE Five priority actions to address the global MDR-TB crisis ACTIONS NEEDED ON ALL FRONTS FROM PREVENTION TO CURE

Projected acceleration of TB incidence decline to target levels Current global trend: -1.5%/year Average -10%/year by 2025 Optimize use of current & new tools emerging from pipeline, pursue UHC and social protection 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. Introduce new tools: a vaccine, a new easier prophylaxis & treatment regimen, a PoC test -5%/year Average -17%/year