1. EMERGING INFECTIOUS DISEASES: A CONTINUOUS CHALLENGE FOR EUROPE STOA-AVIESAN WORKSHOP JUNE 19TH 2012; EUROPEAN PARLIAMENT; BRUXELLES A sustainable agenda for tuberculosis control and research Robert Loddenkemper Berlin German Central Committee against Tuberculosis European Respiratory Society

2. Die ZEIT 26.Nov. 2006 1970/80 it was assumed that TB is nearly vanquished In 1996 WHO declares TB an emergency in the Europe Region „The return of phthisis“

3. Estimated number of cases Estimated number of deaths 1.45 million (range: 1.2–1.6 million) 8.8 million (range: 8.5–9.2 million) 440,000 (range: 390,000–510,000) All forms of TB Multidrug-resistant TB (MDR-TB) HIV-associated TB 1.1 million (13%) (range: 1.0–1.2 million) 350,000 (range: 320,000–390,000) The Global Burden of TB -2010 about 150,000

4. Main causes for the global TB burden Demographic factors - population growth, age structure Increasing poverty, socioeconomic development - Quality of medical facilities  Situation in penitentiaries HIV epidemic: TB/HIV co- coinfection with TB Inefficient treatment: MDR/XDR tuberculosis Migration 

5. 5 Eradication of Tuberculosis: Problem of LTBI Active TB disease -8,8 million new cases per year - only “peak of iceberg” Latent TB Infection (LTBI) - the “hidden” epidemic - ~2 billion people

6. Incidence of tuberculosis in Europe, 2010* Percentage of tuberculosis foreign- born cases among notified tuberculosis patients in Europe* 2010 418.000 (355-496.000) new cases Incidence 47 (40-55)/100.000 In 18 HPC : 87% of incidence *2012 ECDC-WHO Annual TB-Report In several EU/EEA countries >50% foreign-born cases

7. Percentage of MDR-TB cases among tuberculosis patients with DST results in Europe, 2010 (2012 ECDC-WHO Annual TB-Report) 13 top settings with highest % of MDR-TB among new cases, 2001-2010 (WHO Report 2011) EU/EEA: <3% of new cases Estonia : 18.6%, Latvia: 10.8% Tadjikistan: 57. 5% of new cases Ukraine : 79.4% of previously treated cases XDR-TB: 13.2% in Europe 12.2% in EU/EEA Kazakhstan: in up to 76.6%

8. Percentage of tuberculosis/HIV co- infected patients in Europe, 2010* Russian Federation (new TB/HIV cases 1999-2009) Frolova OP. AIDS 2010 In the EU >10% prevalence in Estonia, Ireland, Malta, the Netherlands, Portugal Outside EU high in Russian Federation, Moldova and Ukraine *2012 ECDC-WHO Annual TB-Report

9. Treatment success rate of new MDR-TB cases in the EU/EEA, 2008 Estimated tuberculosis mortality in Europe, 2010 <60.000 (40-90.000) deaths Mortality 6.8 (5.4-8.3)/100.000 In 18 HPC : 94% of mortality 2012 ECDC-WHO Annual TB-Report

10. Smear-positive sputum: Insufficient for diagnosis of 50% of TB patients, notably HIV/Mtb coinfected individuals. Vaccination: BCG protects toddlers but not their parents. Therapy: Rising incidences of MDR-TB and XDR-TB. Our inability to control TB is due to our neglect over the years. Better measures are needed. If we increase our research efforts today, new measures may become available in a decade. TB control – where are we today? Robert Koch 1843 -1910 Albert Calmette 1863-1933 Camille Guérin 1872- 1961 Selman Waksman 1888-1973 Stefan H.E. Kaufmann 2012

11. Potential effects of new TB vaccines, diagnostics and drugs Targets of Stop TB Partnership/WHO : Reduce prevalence and mortality by half till 2015 as compared to 1990Reduce prevalence and mortality by half till 2015 as compared to 1990 Eliminate TB by 2050 (annual incidence < 1/million populationEliminate TB by 2050 (annual incidence < 1/million population How can this be achieved until 2050?* Pre-exposure vaccine: reduction of incidence by 39 – 52%Pre-exposure vaccine: reduction of incidence by 39 – 52% Drugs with shorter treatment time plus against MDR/XDR-TB: reduction by 10 – 27%Drugs with shorter treatment time plus against MDR/XDR-TB: reduction by 10 – 27% Rapid diagnosis: reduction by 13 – 42%Rapid diagnosis: reduction by 13 – 42% Combined: reduction by 70%Combined: reduction by 70% In addition new products targeted at LTBI requiredIn addition new products targeted at LTBI required * Abu-Raddad et al., PNAS, 2009 ; Kaufmann, Hussey & Lambert, Lancet 2010

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13. Time-to-result: 1 h 45 min GeneXpert Xpert MTB (Rifampicin) Courtesy of S. Rüsch-Gerdes The assay is fully automated with only 3 manual steps at the beginning: Addition of SR to raw sputum and 15 min later, after the sample has been inactivated and liquified, transfer to the Cartridge and in the instrument. All the rest is automated: Sample concentration, removal of inhibitors, ultrasonic lysis of cells and a nested real time PCR.

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16. Prevention is Better than Cure: Vaccination

17. Ottenhoff THM et al. Tuberculosis 2012 Prevention is Better than Cure: Research

18. TB: cost of research Available funding for research & development in TB: ca. 500 million US$ Required funding for research & development of new intervention measures against TB over the next 10 years: ca. 2 billion US$ annually (total ca. 20 billion US$ over 10 years) TB: financial losses Total direct and indirect cost: >20 billion US$ annually!! Stefan H.E. Kaufmann 2012

19. Prevention is Better than Cure: Research TB: cost of research Available funding for research & development in TB: ca. 500 million US$ Required funding for research & development of new intervention measures against TB over the next 10 years: ca. 2 billion US$ annually (total ca. 20 billion US$ over 10 years) TB : total direct and indirect cost >20 billion US$ annually!! Stefan H.E. Kaufmann 2012

20. How to improve the TB emergency situation in the Europe Region? Develop/update National TB control programmes incl. for penitentiary systems Commitment of governments!! Implement Stop TB strategy (DOTS and DOTS-plus) Adress MDR-/XDR-TB and HIV/TB co-infection Build up high quality lab capacity (resistance testing) Concentrate on high risk groups Research and development of new tools (diagnostics, drugs, vaccines, biomarkers) Operational research

21. What may happen in the future? Investment in effective TB control incl. research Poverty,TB neglect, MDR/XDR, HIV Aim of TB Partnership “Elimination of TB in 2050” looks rather utopic! In the contrary, TB situation, at least in Eastern Europe, may even worsen!