Part I Tuberculosis (TB): the Once and Future Plague John D. McKinney Global Health Institute School of Life Sciences École Polytechnique Fédérale de Lausanne (EPFL) The American Society for Cell Biology 1
6000 Population growth 10,000 B.C. to 2000 A.D. Cohen, J.E. (1995) How Many People Can the Earth Support? 5000 4000 3000 2000 1000 0-10,000-8,000-6,000-4,000-2,000 01 2,000 Year (A.D.) Source: Joel E. Cohen (1996) How Many People Can the Earth Support? The American Society for Cell Biology 2
Population growth 1 A.D. to 2000 A.D. Cohen, J.E. (1995) How Many People Can the Earth Support? 6000 5000 4000 Urban Dwellers: 1 in 2 (2000) 3000 2000 Urban Dwellers: 1 in 100 (1800) 1000 0 10 200 400 600 800 1000 1200 1400 1600 1800 2000 Year (A.D.) Source: Joel E. Cohen (1996) How Many People Can the Earth Support? The American Society for Cell Biology 3
Most pathogens enter their hosts via mucosal surfaces The American Society for Cell Biology 4
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Mucociliary Elevator The American Society for Cell Biology 7
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Following infection, the incubation period of TB ranges from a few weeks to a lifetime. Comstock et al. (1974) The prognosis of a positive tuberculin reaction in childhood and adolescence. American Journal of Epidemiology 99: 131-138. The American Society for Cell Biology 9
Stage 1: Primary Lesion The American Society for Cell Biology 10
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Mycobacterium tuberculosis inhibits phagosome maturation in macrophages Kaufmann, S.H. (2004) Ann. Rheum. Dis. 63: 50-56 The American Society for Cell Biology 12
Stage 2: Dissemination The American Society for Cell Biology 13
Stage 3: Secondary Lesions The American Society for Cell Biology 14
Stage 4: Latent Infection The American Society for Cell Biology 15
Stage 5: Reactivation The American Society for Cell Biology 16
The tuberculosis granuloma: protection and pathogenesis Early Granuloma Late Granuloma The American Society for Cell Biology 17
Stage 6: Cavitation The American Society for Cell Biology 18
Stage 6: Cavitation The American Society for Cell Biology 19
Stage 6: Cavitation The American Society for Cell Biology 20
Stage 7: Transmission The American Society for Cell Biology 21
The SEIR model of epidemic dynamics MEASLES Critical community size = 300,000 Susceptible 2 weeks 1 week Exposed Infectious Recovered monthsdecades monthsdecades TUBERCULOSIS Critical community size = 100 The American Society for Cell Biology 22
Causes of death worldwide (total: 57 million) World Health Organization (2004) The World Health Report Respiratory digestive 5.7 million Other 3.7 million Maternal perinatal nutritional 3.5 million Injuries 5.2 million Neoplasms 7.3 million Tuberculosis 1.6 million HIV/AIDS 2.8 million Malaria 1.3 million Cardiovascular 16.7 million Other infections 9.3 million The American Society for Cell Biology 23
TB latency: the iceberg of pathogenesis 2.0 million dead 16.2 million sick 1.9 billion infected 3.9 billion uninfected (for now ) The American Society for Cell Biology 24
TB in the United States 1989-2000 Centers for Disease Control (2000) TB Report 2000 20 US-born Foreign-born 15 10 5 0 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Year The American Society for Cell Biology 25
Most TB victims are young adults Tuberculosis HIV/AIDS Age group 0-4 5-14 15-29 30-44 45-59 60-69 70-79 80+ Females Males Age group 0-4 5-14 15-29 30-44 45-59 60-69 70-79 80+ 0 100 200 300 Deaths (1000s) 0 250 500 750 Deaths (1000s) Source: World health Organization, World Health Report 2003. The full report can be downloaded from http://www.who.int/whr/2003/en/ The American Society for Cell Biology 26
Most TB victims are young adults Tuberculosis Other infections Age group 0-4 5-14 15-29 30-44 45-59 60-69 70-79 80+ Females Males Age group 0-4 5-14 15-29 30-44 45-59 60-69 70-79 80+ 0 100 200 300 Deaths (1000s) 0 750 1,500 2,250 Deaths (1000s) Source: World health Organization, World Health Report 2003. The full report can be downloaded from http://www.who.int/whr/2003/en/ The American Society for Cell Biology 27
Leading causes of global mortality among adults World Health Organization (2003) The World Health Report Mortality (adults aged 15-59) Rank Cause Deaths (1000s) 1 HIV/AIDS 2,279 2 Ischaemic heart disease 1,332 3 Tuberculosis 1,036 4 Road traffic injuries 814 5 Cerebrovascular disease 783 6 Self-inflicted injuries 672 7 Violence 473 8 Cirrhosis of the liver 382 9 Lower lung infections 352 10 COPD 343 The American Society for Cell Biology 28
Leading causes of global mortality among adults World Health Organization (2003) The World Health Report Morbidity (adults aged 15-59) Rank Cause DALYs (1000s) 1 HIV/AIDS 68,661 2 Unipolar depressive disorders 57,843 3 Tuberculosis 28,380 4 Road traffic injuries 27,264 5 Ischaemic heart disease 26,155 6 Alcohol use disorders 19,567 7 Hearing loss, adult onset 19,486 8 Violence 18,962 9 Cerebrovascular disease 18,749 10 Self-inflicted injuries 18,522 The American Society for Cell Biology 29