Global TuberculosisBurden

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

• 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

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

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

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)

Incidence of TB in the world

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

Genetic deletion analysis

What causes TB?

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?

What is done about it?

Evolution of TB Control

The touch of King Charles II was thought to cure Tuberculosis (17th 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 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

Source: World Economic Forum, 2005

TB & Poverty overlap

TB burden vs. Gross National Income

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

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

Trends in incidence by subregion

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

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