Part I Tuberculosis (TB): the Once and Future Plague
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1 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
2 6000 Population growth 10,000 B.C. to 2000 A.D. Cohen, J.E. (1995) How Many People Can the Earth Support? ,000-8,000-6,000-4,000-2, ,000 Year (A.D.) Source: Joel E. Cohen (1996) How Many People Can the Earth Support? The American Society for Cell Biology 2
3 Population growth 1 A.D. to 2000 A.D. Cohen, J.E. (1995) How Many People Can the Earth Support? Urban Dwellers: 1 in 2 (2000) Urban Dwellers: 1 in 100 (1800) Year (A.D.) Source: Joel E. Cohen (1996) How Many People Can the Earth Support? The American Society for Cell Biology 3
4 Most pathogens enter their hosts via mucosal surfaces The American Society for Cell Biology 4
5 The American Society for Cell Biology 5
6 The American Society for Cell Biology 6
7 Mucociliary Elevator The American Society for Cell Biology 7
8 The American Society for Cell Biology 8
9 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: The American Society for Cell Biology 9
10 Stage 1: Primary Lesion The American Society for Cell Biology 10
11 The American Society for Cell Biology 11
12 Mycobacterium tuberculosis inhibits phagosome maturation in macrophages Kaufmann, S.H. (2004) Ann. Rheum. Dis. 63: The American Society for Cell Biology 12
13 Stage 2: Dissemination The American Society for Cell Biology 13
14 Stage 3: Secondary Lesions The American Society for Cell Biology 14
15 Stage 4: Latent Infection The American Society for Cell Biology 15
16 Stage 5: Reactivation The American Society for Cell Biology 16
17 The tuberculosis granuloma: protection and pathogenesis Early Granuloma Late Granuloma The American Society for Cell Biology 17
18 Stage 6: Cavitation The American Society for Cell Biology 18
19 Stage 6: Cavitation The American Society for Cell Biology 19
20 Stage 6: Cavitation The American Society for Cell Biology 20
21 Stage 7: Transmission The American Society for Cell Biology 21
22 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
23 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
24 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
25 TB in the United States Centers for Disease Control (2000) TB Report US-born Foreign-born Year The American Society for Cell Biology 25
26 Most TB victims are young adults Tuberculosis HIV/AIDS Age group Females Males Age group Deaths (1000s) Deaths (1000s) Source: World health Organization, World Health Report The full report can be downloaded from The American Society for Cell Biology 26
27 Most TB victims are young adults Tuberculosis Other infections Age group Females Males Age group Deaths (1000s) ,500 2,250 Deaths (1000s) Source: World health Organization, World Health Report The full report can be downloaded from The American Society for Cell Biology 27
28 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 Cerebrovascular disease Self-inflicted injuries Violence Cirrhosis of the liver Lower lung infections COPD 343 The American Society for Cell Biology 28
29 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, Self-inflicted injuries 18,522 The American Society for Cell Biology 29
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