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Global TuberculosisBurden
Philippe Glaziou
Cancun, December 2009
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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?
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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”
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• Phthisis
• Wasting
• Scrofula
• Pott’s disease
• Lupus vulgaris
• Consumption
• The Captain of the Men of Death
• The White Plague
Tuberculosis: what’s in a name ?
The disease was named Tuberculosis in 1839 by J. L. Schönlein
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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.
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How do we get it?
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Lung cavities rich in TB
bacilli
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Diagnostic discoveries
• 24th 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
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1840 1860 1880 1900 1920 1940 1960
0
100
200
300
400
Initial effect of segregation of poor
consumptives in work house
Segregation of poorconsumptives in enlarged and
improved workhouses infirmaries
Systematic segregation
of consumptives, rich and poor,
In hospitals and sanatoria
Antibioticera
Source: data derived from various sources including T. McKewon. The modern rise of population, London: Edward Arnold 1976.
Year
Stan
dard
ised
noti
ficati
on ra
te
Koch’s discovery
Historical decline of TB, 1840-1960
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Global burden in 2008
9.4 million new cases15% infected with HIV
1.4 million deaths excluding HIV0.5 million deaths in HIV-infected
(25% of 2 million HIV deaths)
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Incidence of TB in the world
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Source: Brosch et al. PNAS 2002; 99: 3684-3689
Genetic deletion analysis
What causes TB?
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Risk factor Relative risk for active TB
disease
Weighted prevalence,
total population
Population Attributable
Fraction
HIV infection 8.3 (6.1-11) 1.1% 7% (5.2-9.6)
Malnutrition 4.0 (2.0-6.0) 17% 34% (14-46)
Diabetes 3.0 (1.5-7.8) 3.4% 6.3% (1.6-19)
Alcohol 2.9 (1.9-4.6) 3.2% 5.7% (2.8-10)
Active smoking 2.6 (1.6-4.3) 18% 23% (9.9-37)
Indoor pollution 1.5 (1.2-3.2) 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?
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What is done about it?
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Evolution of TB Control
The touch of King Charles II was thought to cure Tuberculosis (17th century)
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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
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Treatment Milestones: Sanatorium
• Isolation of TB patients in sanatorium
– Prevention of spread of infection
– Fresh air– Sunshine– Physical exercise
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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:
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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 2005
• 2005 targets missed:– Case detection: 60%; treatment success: 84%
• HIV/AIDS in Africa, drug resistance in Eastern Europe
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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)
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The Stop TB Strategy (2005)
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Why is TB still a problem?
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Nairobi
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Nairobi
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Global burden of TB/HIV
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Source: World Economic Forum, 2005
TB & Poverty overlap
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TB burden vs. Gross National Income
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Central Europe: 5yr+ delay in TB controlAlbania, Bulgaria, Czech, Hungary, Poland, Romania
6000
6500
7000
7500
8000
8500
9000
9500
4000 6000 8000 10000 12000 14000
Average GDP per capita
Av
era
ge
nu
mb
er T
B c
ase
s
1980
1989
1994 1995
1990
2006
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Slow decline of global incidence
Incidence (all) 1990-2008
Ra
te p
er
10
0,0
00
120
125
130
135
140
145
150
1990 1995 2000 2005
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Trends in incidence by subregion
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Mortality (excluding HIV)
Ra
te p
er
10
0,0
00
20
40
60
80
100
15
20
25
30
35
40
5
10
15
20
AFRhigh
EEUR
LAC
1990 1995 2000 2005
20
25
30
35
40
45
50
55
1.0
1.5
2.0
2.5
20
30
40
50
60
AFRlow
EME
SEAR
1990 1995 2000 2005
2
4
6
8
10
12
14
20
40
60
80
100
20
30
40
50
60
70
CEUR
EMR
WPR
1990 1995 2000 2005
Trends in TB mortality by subregion
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http://www.who.int/tb/challenges/xdr/xdr_map_sep09.pdf
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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
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A vaccine to transform TB control?
Source: Young D and Dye C. Cell 2006: 124; 687, DOI 10.1016
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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