Global Tuberculosis Burden Philippe Glaziou Cancun, December 2009

Outline What is TB? How do we get TB? Who develops TB? Trends in global burden What is done about it? Why is TB still a problem? Can we get rid of TB?

Tuberculosis: An Ancient Killer Tubercular decay in skull and spinal bones found in 4000 year old Egyptian mummies Hippocrates around 400 BC: Phthisis is the most common disease of humans and it is nearly always fatal

Phthisis Wasting Scrofula Potts disease Lupus vulgaris Consumption The Captain of the Men of Death The White Plague Tuberculosis: whats in a name ? The disease was named Tuberculosis in 1839 by J. L. Schönlein

Signs and symptoms Early symptoms Common cold symptoms Listlessness, fatigue, fever, a minimally productive cough of yellow or green sputum and a general feeling of malaise. Later symptoms Night sweats, fever, cough with purulent secretions and haemoptysis, dyspnoea, chest pain, and hoarseness appear.

How do we get it?

Lung cavities rich in TB bacilli

Diagnostic discoveries 24 th March 1882 (Robert Koch) TB Day –Discovery of staining technique that identified Tuberculosis bacillus 1890 (Robert Koch) –Tuberculin discovered –Diagnostic use when injected into skin 1895 (Roentgen) –Discovery of X-rays –Early diagnosis of pulmonary disease

Initial effect of segregation of poor consumptives in work house Segregation of poor consumptives in enlarged and improved workhouses infirmaries Systematic segregation of consumptives, rich and poor, In hospitals and sanatoria Antibiotic era Source: data derived from various sources including T. McKewon. The modern rise of population, London: Edward Arnold Year Standardised notification rate Kochs discovery Historical decline of TB,

Global burden in million new cases 15% infected with HIV 1.4 million deaths excluding HIV 0.5 million deaths in HIV-infected (25% of 2 million HIV deaths)

Incidence of TB in the world

Source: Brosch et al. PNAS 2002; 99: Genetic deletion analysis What causes TB?

Risk factorRelative risk for active TB disease Weighted prevalence, total population Population Attributable Fraction HIV infection8.3 (6.1-11)1.1%7% ( ) Malnutrition4.0 ( )17%34% (14-46) Diabetes3.0 ( )3.4%6.3% (1.6-19) Alcohol2.9 ( )3.2%5.7% (2.8-10) Active smoking2.6 ( )18%23% (9.9-37) Indoor pollution1.5 ( )71%26% (12-61) From Lonnroth K et Al. Global epidemiology of tuberculosis. Seminars in Respiratory and Critical Care Medicine, 3 March 2008 Who develops TB?

What is done about it?

Evolution of TB Control The touch of King Charles II was thought to cure Tuberculosis (17 th century)

Prevention Milestone: BCG BCG developed by Calmette & Guerin in 1907 First human immunizations in 1921 in France Protection against serious forms of TB Limited or no protection against pulmonary TB

Treatment Milestones: Sanatorium Isolation of TB patients in sanatorium –Prevention of spread of infection –Fresh air –Sunshine –Physical exercise

TB Drugs 1943: Selman Waksman discovers Streptomycin (Nobel Prize in 1952) 1949: PAS 1952: Isoniazid 1954: Pyrazinamide 1955: Cycloserine 1962: Ethambutol 1963: Rifampicin Other anti-TB drugs:

World Health Assembly Targets for Global TB Control By 2000: –Detect 70% of all new sputum smear-positive cases –Successfully treat 85% Slow progress of many countries led to the revision of the target year to targets missed: –Case detection: 60%; treatment success: 84% HIV/AIDS in Africa, drug resistance in Eastern Europe

Emergence of worst-case TB scenarios Co-infection between TB and HIV Multidrug-resistant TB (MDR-TB) –Resistance to isoniazid and rifampin – the 2 most powerful anti-TB drugs Extensively-drug resistant TB (XDR- TB) –MDR-TB plus resistance to any fluoroquinolone and at least 1 second-line injectable (AMI, KAN, CAP)

The Stop TB Strategy (2005)

Why is TB still a problem?

Nairobi

Global burden of TB/HIV

Source: World Economic Forum, 2005 TB & Poverty overlap

TB burden vs. Gross National Income

Central Europe: 5yr+ delay in TB control Albania, Bulgaria, Czech, Hungary, Poland, Romania Average GDP per capita Average number TB cases

Slow decline of global incidence

Trends in incidence by subregion

Trends in TB mortality by subregion

Can we get rid of TB? New vaccines –BCG does not prevent the disease in adults New diagnostics –Smear microscopy and culture: imperfect and slow –Drug susceptibility testing too slow New drugs –Treatment is still much too long –To treat drug resistant TB: MDR-TB, XDR-TB

A vaccine to transform TB control? Source: Young D and Dye C. Cell 2006: 124; 687, DOI

In conclusion Burden exacerbated in the 90s by the rise of HIV Slow progress of TB control performance Slow decline in disease burden since 2004 Elimination nowhere in sight, we need –New vaccines –New drugs –New diagnostics