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PATHOGENS AND PARASITES PLAGUES AND PANDEMICS

PATHOGENS AND PARASITES PLAGUES AND PANDEMICS. CHRISTOPHER DYE. Animation: Shih Ching Fu. The Great Escape. Life expectancy in England 1300-2000. 80. Wrigley & Schofield. Human Mortality Database. 70. Clark. 60. 50. Life expectancy at birth (years). 40. 30. 20. 1300. 1400. 1500.

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PATHOGENS AND PARASITES PLAGUES AND PANDEMICS

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  1. PATHOGENS AND PARASITES PLAGUES AND PANDEMICS CHRISTOPHER DYE Animation: Shih Ching Fu

  2. The Great Escape Life expectancy in England 1300-2000 80 Wrigley & Schofield Human Mortality Database 70 Clark 60 50 Life expectancy at birth (years) 40 30 20 1300 1400 1500 1600 1700 1800 1900 2000

  3. PATHOGENSPARASITESPLAGUESPANDEMICS • How many kinds of pathogens are there, and what kinds of diseases do they cause? What are we and why do we suffer? • How do pathogens spread and persist? How does epidemiology explain parasite lifestyles? • What epidemics will we face in future? What are "the coming plagues"?

  4. Parasites and diseases

  5. Life's three domainsArchaea Bacteria Eukaryotes Archaea -- one cell -- few parasites? (Extreme bacteria) Bacteria -- one cell -- parasites, commensals, mutualists… Eukaryotes – one or many cells -- protozoa (malaria), fungi (ringworm), worms (hookworm), insects, arachnids (ticks)

  6. Non-living pathogensViruses Prions Parasitic DNA Viruses -- genes in a protective protein shell -- Ebola, measles, polio, cancers Prions -- infectious protein particles -- transmissible spongiform encephalopathies (TSEs) -- Creutzfeld-Jakob disease (kuru, vCJD), bovine spongiform encephalopathy (BSE or mad cow disease) Parasitic DNA -- transposons -- mobile genetic elements -- heritable disorders -- hemophilia, severe combined immunodeficiency, porphyria, cancer

  7. People are mostly bacteriaHumans + bacteria = "super-organisms" Humans Functional cells (other than blood, neurons ) 1012 Bacteria (Bacterioides, Clostridium, Escherichia…) On skin 1012 In mouth 1010 In gut 1014 >1kg >1000 species >100 × as many genes

  8. From the power of partnership… … to the perils of parasitism

  9. Vibrios: mutualists and pathogens ← Ganges Delta: Vibrio (cholera) mixing pool Vibrio fischeri: drives light organs of squids → ←Vibrio cholerae: potentially lethal human diarrhoea

  10. 1415 organisms pathogenic to humans (exc. arthropods) • Viruses & prions 217 • Bacteria & rickettsia 538 • Fungi 307 • Protozoa 66 • Helminths (worms) 287 • Zoonotic (from animals) 868 • "Emerging" 175 Source: Taylor et al 2001

  11. Where 60 million people die double burden of disease in low-income countries 8 Low-middle income High income 6 Deaths per million population 4 2 0 Communicable, Non- Injuries pregnancy, communicable nutrition

  12. Infectious causes of death in ICD-10 4 13/60m deaths in 2002 from infections 3 86% caused by top 5 Millions of deaths in 2002 2 1 0 Malaria Measles Tetanus HIV/AIDS Pertussis Diarrhoea Hepatitis B Meningitis* Tuberculosis STDs exc HIV Low respiratory Tropical diseases

  13. 2. Parasite spread and persistence in populations

  14. Concepts and models "All that is simple is false and all that is complex is useless" P Valéry "Everything should be made as simple as possible, but not simpler" A Einstein Why replace a world you don't understand with a model of the world you don't understand? P Richardson & R Boyd

  15. Reproduction and persistence: the key to epidemiology and evolution Basic case reproduction number: R0 = 15/9 = 1.8 (>1) Epidemic wanes as pathogen runs out of hosts (death, immunity)

  16. Measles can't survive on small islands 1 Tonga Fr. Polynesia Gilbert Is. Cook Is. Greenland 0.8 Samoa New Hebrides Faroe Is. Solomon Is. New 0.6 Caledonia Proportion months with no cases Iceland Fiji Bermuda 0.4 Guam 0.2 Hawaii 0 0.1 1 10 Population size (millions)

  17. Measles: penalty for living in cities 0.7 Cities with most measles have: High birth and immigration rates (>200,000 per yr) Poor vaccination coverage Source: Strebel 2001 Moderate-high Lagos incidence Dhaka Low incidence 0.6 Karachi 0.5 Mumbai Jakarta 0.4 Annual growth rate (millions) 0.3 Los Sao Paolo 0.2 Angeles Rio de J New York 0.1 Mexico Buenos Tokyo City Aires 0 5 10 15 20 25 30 Population 2000 (millions)

  18. Measles in the UKlower vaccine uptake leads to larger outbreaks Jansen: Science 301, 804 (2003)

  19. TB: a human disease for 3 million years? time present: M tuberculosis complex bottleneck 35 000 yrs BP 3 million yrs BP: ancestral smooth tubercle bacilli Source: Gutierrez PLoS Pathogens Sep 2005

  20. Signs of silent TB infection Tuberculin or Mantoux test

  21. Plague – Yersinia pestisrats – fleas – people

  22. Rats as plague reservoirs plague cases in rats human infections

  23. London, Thames, summer 1858 "The Great Stench" "The sewage of three millions of people has been brought… to seethe and ferment… in one vast open cloaca… Parliamentary committee rooms rendered barely tolerable…" Winslow 1943

  24. Notes on Nursing What It Is, and What It Is Not by F Nightingale, 1860 "of the fatal effects of the effluvia from excreta it would seem unnecessary to speak were they not so constantly neglected" F Nightingale

  25. The Great Stink of Paris and the Nineteenth-Century Struggle Against Filth and Germsby David S. Barnes, 2006 Clearing the air: Dr. André-Justin Martin led the municipal disinfection service in 1890s Paris

  26. Morbid matters: cholera London July-Aug 1854 Both companies Southwark & Vauxhall 32 deaths/1000 Lambeth 4 deaths/1000

  27. 3. Future plagues

  28. The growth of literature on new threats from infection

  29. malaria Drug resistance Beijing TB AIDS SARS Bird flu

  30. Situations vacant opportunities for new pathogens Source: Taylor et al 2001

  31. Beijing TB strains kill mice quickly 100 80 Control strain H37Rv 60 Percent surviving 40 20 Beijing strains 0 0 2 4 6 8 10 12 Weeks Cin Exp Imm v133 p30 (2003)

  32. Beijing/W TB strains tend to be in younger people in Viet Nam and Africa Source: EID v12 p736 (2006) 80 China 60 Viet Nam Percent strains Beijing 40 3 African countries 20 0 <30 30-49 50+ Age group (yr)

  33. The (re)growing problem of hospital infection Directly Rostov entered the [hospital] he was enveloped by a smell of putrefaction… "What do you want, sir?" said the doctor. The bullets having spared you, do you want to try typhus? This is a pesthouse, sir." "How so?" asked Rostov. "Typhus, sir. It's death to go in. Tolstoy, War and Peace (Ch XVII)

  34. Evolution as seen in the ERMethicillin-resistant Staphylococcus aureus (MRSA) • Commonest cause of skin and soft tissue infections in USA -- now in the "community" • Also resistant to oxacillin, penicillin and amoxicillin • USA 2004: 320 of 422 adults had "staph" -- 78% of these had MRSA Source: NEJM v355 p666 2006

  35. Ebola and CCHF Influenza H5N1 Hantavirus Lassa fever Monkeypox Nipah Hendra NV-CJD Rift Valley Fever SARS CoV VEE Yellow fever West Nile Brucellosis E Coli O157 Multidrug resistant Salmonella Plague Emerging and re-emerging zoonoses, 1996–2004 Cryptospporidiosis Leptospirossis Lyme Borreliosis

  36. Apocalypse soon? • Unavoidable transmission route • Highly infectious • High proportion of people exposed • Transmission rapid compared with response time (everyone gets infected before knowing) • Fatal

  37. INFECTION TRANSMITTED VIA THE GLOBAL AVIATION NETWORK?

  38. Real spread from China & Hong Kong SARS Severe acute respiratory syndrome Origin bats in China Transmission among humans Case fatality 4% – up to 1000 deaths Model spread from Hong Kong

  39. Confirmed Human and Animal H5N1 Infections since 2003 and Poultry Distribution

  40. Hong Kong Flu H3N2 Spanish Flu H1N1 Asian Flu H2N2

  41. How to survive a flu pandemic? • During a pandemic • Wash your hands often • Avoid people • Don't flee the city • Get infected early – if you dare • Source: New Sci, 7 Jan 2006 In advance • Stockpile Tamiflu or Relenza - and hope • Get pneumococcus vaccination • Consider taking statins • Become indispensable • Stock up emergency supplies • Move to a rich country

  42. 12 1 3 4 5 8 9 6 14 15 16 7 10 2 13 25 years of AIDS People living with HIV 50 9 In 1991-1993, HIV prevalence in young pregnant women in Uganda and in young men in Thailand begins to decrease 45 Million 40 1 Immune deficiency in gay men in USA 2 Acquired Immune Deficiency Syndrome (AIDS) is defined 35 10 Highly Active Antiretroviral Treatment launched 3 The Human Immune Deficiency Virus (HIV) is identified as the cause of AIDS 30 11 HIV infected in 2005: 40 million Died in 2005: 3 million Total deaths: 25 million Children orphaned by AIDS in sub-Saharan Africa 25 4 In Africa, a heterosexual AIDS epidemic is revealed 20 8 The first therapy for AIDS – zidovudine, or AZT -- is approved for use in the USA 15 10 5 0 2005 1980 1985 1990 1995 2000 1.1

  43. A global view of HIV infection 38.6 million people [33.4‒46.0 million] living with HIV, 2005 0.1%+ <0.1%+ 1%+ 5%+ 0.5%+ 15%+ HIV infection in adults

  44. From natural history to public health • Parasitism adopted as a "lifestyle" by many kinds of living and non-living agents what is self and non-self? • Despite huge parasite diversity, very few cause most human deaths most are preventable or curable • Pandemics most likely to be a lethal virus with transmission rapid compared with reaction time influenza (weeks), HIV/AIDS (years)

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