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Animation: Shih Ching Fu CHRISTOPHER DYE PATHOGENS AND PARASITES PLAGUES AND PANDEMICS Life expectancy at birth (years) The Great Escape 80 Life expectancy in England 1300-2000 Wrigley & Schofield 70 Human Mortality Database Clark 60 50 40 30 20 1300 1400 1500 1600 1700 1800 1900 2000 PATHOGENS PARASITES PLAGUES PANDEMICS • 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"? 1. Parasites and diseases Life's three domains Archaea 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) Non-living pathogens Viruses 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 People are mostly bacteria Humans + 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 From the power of partnership… … to the perils of parasitism Vibrios: mutualists and pathogens ← Ganges Delta: Vibrio (cholera) mixing pool Vibrio fischeri: drives light organs of squids → ← Vibrio cholerae: potentially lethal human diarrhoea • • • • • Viruses & prions Bacteria & rickettsia Fungi Protozoa Helminths (worms) • Zoonotic (from animals) • "Emerging" 217 538 307 66 287 868 175 Source: Taylor et al 2001 1415 organisms pathogenic to humans (exc. arthropods) Deaths per million population Where 60 million people die double burden of disease in low-income countries 8 6 Low-middle income High income 4 2 0 Communicable, pregnancy, nutrition Noncommunicable Injuries Infectious causes of death in ICD-10 Millions of deaths in 2002 4 3 2 1 0 13/60m deaths in 2002 from infections 86% caused by top 5 2. Parasite spread and persistence in populations D 1000.0 100.0 10.0 1.0 0 20 40 0.1 0 15 30 Concepts and models 60 45 60 80 75 90 "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 Reproduction and persistence: the key to epidemiology and evolution No. cases per generation 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 Generations of cases Basic case reproduction number: R0 = 15/9 = 1.8 (>1) Epidemic wanes as pathogen runs out of hosts (death, immunity) Proportion months with no cases Measles can't survive on small islands 1 0.8 Tonga Gilbert Is. Fr. Polynesia Cook Is. Greenland Samoa New Hebrides Faroe Is. Solomon Is. New Caledonia 0.6 Iceland Bermuda 0.4 Fiji Guam 0.2 Hawaii 0 0.1 1 Population size (millions) 10 Measles: penalty for living in cities 0.7 Annual growth rate (millions) Dhaka 0.6 Karachi 0.5 Cities with most measles have: Moderate-high incidence Low incidence Lagos Mumbai High birth and immigration rates (>200,000 per yr) Jakarta 0.4 0.3 0.2 Rio de J 0.1 Buenos Aires Los Angeles Sao Paolo New York Mexico City Poor vaccination coverage Tokyo 0 5 10 15 20 25 Population 2000 (millions) 30 Source: Strebel 2001 Measles in the UK lower vaccine uptake leads to larger outbreaks 70 Jansen: 0.4 Science 301, 804 (2003) 0.6 0.3 80 50 reproduction numbers 0.9 0.7 0.8 60 40 0.8 30 40 20 20 10 0 0 1995 1996 1997 1998 1999 2000 2001 2002 2003 Vaccine uptake (%) Cases in outbreak 60 100 TB: a human disease for 3 million years? time present: M tuberculosis complex bottleneck 35 000 yrs BP Source: Gutierrez PLoS Pathogens Sep 2005 3 million yrs BP: ancestral smooth tubercle bacilli Signs of silent TB infection Tuberculin or Mantoux test Plague – Yersinia pestis rats – fleas – people >120,000 London plague deaths, 1590-1650 from Graunt's Bills of Mortality Deaths (10,000s/yr) 4 3 2 1 0 1590 1597 1604 1611 1618 1625 1632 1639 1646 Rats as plague reservoirs plague cases in rats human infections 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 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 The Great Stink of Paris and the Nineteenth-Century Struggle Against Filth and Germs by David S. Barnes, 2006 Clearing the air: Dr. André-Justin Martin led the municipal disinfection service in 1890s Paris Morbid matters: cholera London July-Aug 1854 Both companies Southwark & Vauxhall 32 deaths/1000 Lambeth 4 deaths/1000 3. Future plagues The growth of literature on new threats from infection malaria Drug resistance Beijing TB AIDS SARS Bird flu Situations vacant opportunities for new pathogens Viruses pose the greatest risk number emerging 72 18 6 11 30 60 20 24 10 10 8 6 0 viruses bacteria fungi protozoa humans animals humans animals humans animals humans animals humans 0 worms Source: Taylor et al 2001 40 animals % species emerging 50 Beijing TB strains kill mice quickly Percent surviving 100 80 Control strain H37Rv 60 40 20 Beijing strains 0 0 2 4 Cin Exp Imm v133 p30 (2003) 6 Weeks 8 10 12 Percent strains Beijing 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 40 3 African countries 20 0 <30 30-49 Age group (yr) 50+ 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) Evolution as seen in the ER Methicillin-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 Emerging and re-emerging zoonoses, 1996–2004 Ebola and CCHF Influenza H5N1 Hantavirus Lassa fever Monkeypox Nipah Hendra NV-CJD Rift Valley Fever Brucellosis SARS CoV Cryptospporidiosis E Coli O157 VEE Leptospirossis Multidrug resistant Salmonella Yellow fever Lyme Borreliosis Plague West Nile Apocalypse soon? • • • • Unavoidable transmission route Highly infectious High proportion of people exposed Transmission rapid compared with response time (everyone gets infected before knowing) • Fatal INFECTION TRANSMITTED VIA THE GLOBAL AVIATION NETWORK? 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 Confirmed Human and Animal H5N1 Infections since 2003 and Poultry Distribution How many people will die in the next flu pandemic? Millions of flu deaths 50 Re-running the 3 pandemics of the 20th century 40 30 20 10 Spanish Flu H1N1 Asian Flu H2N2 Hong Kong Flu H3N2 1957-58 1968-70 0 1918-20 How to survive a flu pandemic? 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 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 25 years of AIDS People living with HIV Million 50 45 40 35 30 25 20 15 1 Immune deficiency in gay men in USA 2 Acquired Immune Deficiency Syndrome (AIDS) is defined 3 The Human Immune Deficiency Virus (HIV) is identified as the cause of AIDS 4 In Africa, a heterosexual AIDS epidemic is revealed 8 The first therapy for AIDS – zidovudine, or AZT -- is approved for use in the USA 10 5 1 2 3 4 5 6 9 15 16 14 9 In 1991-1993, HIV prevalence in young pregnant women in Uganda and in young men in Thailand begins to decrease 10 Highly Active Antiretroviral Treatment launched 13 11 10 12 7 8 Children orphaned by AIDS in subSaharan Africa 1985 Died in 2005: 3 million Total deaths: 25 million 0 1980 HIV infected in 2005: 40 million 1990 1995 2000 2005 1.1 A global view of HIV infection 38.6 million people [33.4‒46.0 million] living with HIV, 2005 0.1%+ <0.1%+ 1%+ 0.5%+ 5%+ 15%+ HIV infection in adults 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)