Why can t we eliminate tuberculosis?

Why can t we eliminate tuberculosis? Neil W. Schluger, M.D. Professor of Medicine, Epidemiology and Environmental Health Sciences Columbia University Chief Scientific Officer World Lung Foundation

Current trajectory of the global TB epidemic Dye et al. Ann Rev Pub Health 2013; 34: 271-286 year

What we need to do to eliminate tuberculosis Invest in public health Invest in research Embrace new ideas and new technology Take MDR-TB seriously Stop doing stupid stuff Speak with a louder voice

Invest in public health, with money, effort and energy Better surveillance Improve access to care Insure drug supply Do a better job of monitoring and encouraging adherence to therapy

Notifications of TB cases have stabilized in recent years, and in 2013 represented 64% (range, 61 66%) of estimated incident cases. The gap between notifications and incident cases an estimated total of 3.3 million cases can be explained by a mixture of underreporting of diagnosed TB cases (for example, failure to notify cases diagnosed in the private sector) and under-diagnosis due to poor access to health care and/or failure to detect cases when people visit health care facilities. Major efforts are needed to ensure that all cases are detected, notified to national surveillance systems, and treated according to international standards. WHO Global TB Report 2014, pg. 39

WHO, Global TB Report 2014

Costs of tuberculosis care as a percentage of annual income Tanimura et al. Eur Resp J 2014; 43: 1763-1775

Financial coping strategies of tuberculosis patients Tanimura et al. Eur Resp J 2014; 43: 1763-1775

Drug shortages MMWR 2013; 62: 398

A tale of two cities: New York and London TB Incidence 2013: 8.6/100,000 Source: NYC DOHMH TB Incidence 2013: 37/100,000 Source: Public Health England

A tale of two countries: U.S. and South Korea TB, Republic of Korea, 1990-2013 TB Incidence 2013: 3.1/100,000 TB Incidence 2013: 97/100,000 Source: WHO

Turning the tide--tb control in New York Implementation of directly observed therapy (DOT) Public health advisors Rebuild TB clinics Infection control Use of standardized regimens for treatment $40 million annually from CDC Frieden et al. N Eng J Med 1995; 333: 229-233

What we need to do to eliminate tuberculosis Invest in public health Invest in research Embrace new ideas and new technology Take MDR-TB seriously Stop doing stupid stuff Speak with a louder voice

TAG Report 2014

Deaths 1.5 million 1.6 million 0.62 million 0 TAG Report 2014

The cost of underinvestment in TB research Only 2 new drugs approved in 40 years In that time period, HIV infection has become manageable, and hepatitis C infection has become curable. No prospect of approval of a more effective vaccine in the next 10 years In most places in the world, TB is diagnosed the same way it was diagnosed over 120 years ago The pace of clinical trials is agonizingly slow

Drugs in the clinical pipeline for the world s leading causes of mortality Leading causes of global mortality: 1. Ischemic heart disease 2. Stroke 3. COPD 4. Lower respiratory infection 5. Lung cancer 6. HIV/AIDS 7. Diarrhea 8. Road traffic accidents 9. Diabetes 10.Tuberculosis 11.Malaria Drugs in clinical development: - Heart disease and stroke: >200 - COPD: >50 - Antibacterials and antivirals: 394 (drugs and vaccines) - ( 124 for pneumonia and TB ) - Cancer: 800 - Lung Cancer: 121 - Breast Cancer: 111 - HIV/AIDS: 44 (includes vaccines) - Diabetes: 180 - Anti-tuberculosis: 5-8 - Anti-malarials: 6 Sources: The Global Burden of Disease Report The Pharmaceutical Research and Manufacturers of America (www.pharma.org), accessed Feb. 25, 2015

TB trials are too slow 2500 study subjects Trial initiated 2007 Paper published 2014 8000 study subjects Trial initiated 2001 Paper published 2011 Why so slow? Endpoints are the same as those used since the original BMRC streptomycin trial in 1948, and clinical trials capacity is limited.

What we need to do to eliminate tuberculosis Invest in public health Invest in research Embrace new ideas and new technology Take MDR-TB seriously Stop doing stupid stuff Speak with a louder voice

The TB community s attitude towards new technology?

Lancet 2014; 383: 424-435

Xpert MTB/RIF What it does do: Diagnoses TB and determines susceptibility to rifampin accurately and rapidly What it does not do: Fix your TB control program Cure cancer Achieve world peace

Interventions and their effect on TB cases Dye et al. Ann Rev Pub Health 2013; 34: 271-286

What we need to do to eliminate tuberculosis Invest in public health Invest in research Embrace new ideas and new technology Take MDR-TB seriously Stop doing stupid stuff Speak with a louder voice

Distribution and prevalence of MDR-TB New cases Retreatment cases Total MDR cases: 480,000 WHO WHO Global 2010 TB Global Report, Report 2014

Male/female ratio: case notifications Health expenditures (US $ per MDR-TB in Africa: the more you look, capita) *MDR, multidrug resistance; TB, tuberculosis; ss+, sputum sample positive. Based on presurvey minus postsurvey values. A negative Z-score is indicative of an increase over time. Marginally statistically significant trend (p<0.10). the more you find Statistically significant trend (p<0.05). Report published in 2004 have MDR TB rates >2.0% of all combined TB cases. This finding suggests that completing DRSs for all or most countries in the AFRO region is urgently needed and that the MDR TB threat in Africa could be much higher than originally assessed by WHO in its 36, 1.5, 1.5 0.7 2.6 0.4 39, 107, 51 15 689 131 previous report in 2004. Drug-resistant strains, along with HIV/AIDS, are causing the biggest challenge to efficient management and control of TB. The lower rates of MDR TB in Africa, when compared with rates in Eastern Europe or South America, could be Figure. Prevalence of multidrug resistance (MDR) in Africa among combined tuberculosis cases. A) Data collected from the Third Global Report on Anti-tuberculosis Drug Resistance in the World of the World Health Organization (WHO) published in 2004 (40). B) Data from various recent WHO publications, peer-reviewed journal articles, and WHO s Fourth Global Report (1). C) Formulaic estimates of Zignol et al. (11). AFRO, WHO Regional Offi ce for Africa. Emerg Infect Dis 2008; 14: 1345-1352 Emerging Infectious Diseases www.cdc.gov/eid Vol. 14, No. 9, September 2008 1349

Diagnosis and treatment of MDR TB in the world WHO Global TB report, 2014

What we need to do to eliminate tuberculosis Invest in public health Invest in research Embrace new ideas and new technology Take MDR-TB seriously Stop doing stupid stuff Speak with a louder voice

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