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”
Tuberculosis: what’s in a name ?

• Phthisis
The disease was named
Tuberculosis in 1839
• Wasting
by J. L. Schönlein
• Scrofula
• Pott’s disease
• Lupus vulgaris
• Consumption
• The Captain of the Men of Death
• The White Plague
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
• 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
 Historical decline of TB, 1840-1960
400
Standardised notification rate

Segregation of poor
consumptives in enlarged and
improved workhouses infirmaries
300

Systematic
Koch’s segregation
discovery of
200 consumptives,
rich and poor,
In hospitals and
sanatoria Antibiotic
era
100
Initial effect of
segregation of poor
consumptives in
work house
0
1840 1860 1880 1900 1920 1940 1960
Year
Source: data derived from various sources including T. McKewon. The modern rise of population, London: Edward Arnold 1976.
 Global burden in 2008
9.4 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
 What causes TB?

Genetic deletion analysis

Source: Brosch et al. PNAS 2002; 99: 3684-3689

 Who develops TB?
Risk factor Relative risk Weighted Population
for active TB prevalence, total Attributable Fraction
disease population

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)

rom Lonnroth K et Al. Global epidemiology of tuberculosis. Seminars in Respiratory and

ritical Care Medicine, 3 March 2008
What is done about it?
 Evolution of TB Control

The touch of King Charles II was thought to

cure Tuberculosis
 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)

Other anti-TB drugs:

• 1949: PAS • 1955: Cycloserine
• 1952: Isoniazid • 1962: Ethambutol
• 1954: Pyrazinamide
• 1963: Rifampicin
 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
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
Nairobi
Global burden of TB/HIV
TB & Poverty overlap

Source:
World Economic
Forum, 2005
TB burden vs. Gross National Income
 Central Europe: 5yr+ delay in TB control
Albania, Bulgaria, Czech, Hungary, Poland, Romania
9500
1980
9000
Average number TB cases

8500 1994 1995

8000

7500

7000
1990
6500 1989
2006
6000
4000 6000 8000 10000 12000 14000
Average GDP per capita
Slow decline of global incidence
150

145

140
Rate per 100,000

135

130

125

120

1990 1995 2000 2005

Incidence (all) 1990-2008
Trends in incidence by subregion
Trends in TB mortality by subregion
AFRhigh AFRlow CEUR
100 55 14
50 12
80 45
10
40
60 8
35
30 6
40
25 4
20 20
2

EEUR EME EMR

40 100
Rate per 100,000

35 2.5
80
30 2.0
60
25
1.5 40
20

15 1.0 20

LAC SEAR WPR

60 70
20
60
50
50
15
40 40
10 30 30

20
5 20
1990 1995 2000 2005 1990 1995 2000 2005 1990 1995 2000 2005

Mortality (excluding HIV)

http://www.who.int/tb/challenges/xdr/xdr_map_sep09.pdf
 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 10.1016
 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