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Senior Freshman BY2209 Infection & Immunity Lecture 1: Infectious Diseases i the in th 21st Century C t Prof Jay Hinton, Microbiology Department Senior Freshman BY2209 Infection & Immunity Course Overview ● Joint course, delivered by Microbiology, Immunology & Genetic Departments ● An exciting multi-disciplinary course focusing on: Key bacterial pathogens and how they cause disease Strategies for controlling infections Vaccines & Antibiotics How H h humans cope with ith iinfections... f ti Immune responses Genetic susceptibility to infectious disease Why is this one of the most important courses you’ll do this year at Trinity? ● Because Infectious Disease has had a huge effect on shaping the world ... A question... ● “Why has life expectancy doubled in the past 150 years?” Average Age of Death, England 1837 1841 1837-1841 Manchester (Manufacturing) Liverpooll (Commercial) Wiltshire (Agriculture) “Persons” & G t Gentry Tradesmen & F Farmers Labourers & S Servants t 38 20 17 35 22 15 50 48 33 ● If this thi was 1840... 1840 Some of you would be dead Many of your parents would be dead Aiello et al., (2008) Am. J. Infect. Control 36: S111-115 Average Age of Death, England 1837 1841 1837-1841 Manchester (Manufacturing) Liverpool (Commercial) Wilts (A i lt (Agriculture) ) “Persons” & Gentry Tradesmen & Farmers Laborers & Servants 38 20 17 35 22 15 50 48 33 Average life expectancy increased between 19th & 20th Centuries ● From 40 (1848) ( ) ● ......to 69 (1970) http://www.ohe.org/page/knowledge/schools/appendix/life_expectancy.cfm Male Life expectancy, Ireland 1926 & 1999 80 70 60 57 50 40 2000 1975 Year 1950 1925 30 1900 Av verage e age at de eath 77 Male Life expectancy U.S.A. 1900-99 WW II 70 HIV/ AIDS 60 Irish male life expectancy 50 40 2000 1975 Year 1950 30 1925 “Spanish” Flu pandemic (1918) 1900 Av verage e age at de eath 80 Epidemics in New York City, 1804 -1918 1918 Aiello et al., al (2008) Am. Am J. J Infect. Infect Control 36: S111 S111-115 115 Leading causes of death, USA ● ● ● ● Diptheria Diarrhoeal disease TB Pneumonia 1900 ● Pneumonia P i 1998 Aiello et al., (2008) Am. J. Infect. Control 36: S128-151 Death from all infectious diseases USA 1900 to 1996 USA, 1000 “Spanish” Flu pandemic (1918) 800 Mortality per 100,000 per year 600 First use of Penicillin 400 Polio vaccine introduced Chlorination of water supplies 200 1900 1920 1940 1960 1980 Year source: Centers for Disease Control Infectious disease ● Infectious disease has had a huge effect on the human race ● History has been shaped by a plethora of epidemics and pandemics ●U Until til we started t t d tto understand d t d the th causes off disease, we were unable to fight it... What causes disease? (Pre-1850) ● Miasmatic theory Disease was transmitted by miasma A p poisonous vapour p or mist ● Cholera “miasma” transmitted in the wind Germ Theory (post 1850) ● Proposed that microorganisms are the cause of many diseases ● Highly g y controversial when first proposed p p ● Cornerstone of modern medicine & clinical microbiology ● Led to antibiotics and hygienic practices… Louis Pasteur 1822 – 1895 Developed Pasteurisation in 1864 Saved Millions of lives… Robert Koch 1843-1910 ● Founder of public health… ● Developed “Koch’s Postulates” (next lecture!) In late 1800’s discovered causal agents of: ● Tuberculosis, ● Mycobacterium y tuberculosis ● Cholera ● Vibrio cholerae ● Anthrax. Bacillus anthracis Vaccination ● Immunity to disease can be generated by vaccination ● Important role in protecting individuals against illness ● Vaccination works by safely exposing individuals to a specific pathogenic microbe Artificially increases immunity Vaccination Mortality due to Tuberculosis 1850 1970 1850-1970 Mycobacterium tuberculosis Aiello et al., ((2008)) Am. J. Infect. Control 36: S116-127 Eradication of Diptheria in England 1860 - 1970 Corynebacterium diphtheriae Aiello et al., (2008) Am. J. Infect. Control 36: S116-127 Worldwide eradication of Smallpox by vacccination ● Began in 1950 Rahima Banu (aged 2) Last human case (1975) ● Declared successful in 1980 Image: WHO Eradication of Polio in USA by vaccination 1950 vaccination, 1950-1990 1990 Aiello et al., ((2008)) Am. J. Infect. Control 36: S116-127 Vaccines ● Measles vaccine introduced in 2000 In 8 years, global deaths reduced by 78% ● 500,000 lives saved in 2008 ● Estimate that 4.2 million p people p died in 2005 due to vaccine-preventable diseases 30th January, y, 2010 http://www.gatesfoundation.org/GlobalHealth/Pri_Diseases/Vaccines/Vaccine_Backgrounder.htm Antibiotic treatment of pneumonia saves lives in USA USA, 1900 - 1970 Aiello et al., (2008) Am. J. Infect. Control 36: S116-127 How did we control infectious disease? ● Vaccination ● Antibiotics ● Public health measures Public sanitation Chlorination of water supply Aiello et al., (2008) Am. J. Infect. Control 36: S128-151 Incidence of typhoid, typhoid USA * Chlorination of water supply How did we control infectious disease? ● Vaccination ● Antibiotics ● Public health measures Public sanitation Chlorination of water supply ● Social measures Improving housing Reducing poverty & over over-crowding crowding Personal Hygiene! ● Handwashing reduces incidence of: Diarrhoeal disease Flu & Colds Life expectancy increased... ● Everything looked very good in the 1960s! 1000 800 y Mortality per 100,000 per p year 600 First use of P i illi Penicillin 400 Polio vaccine introduced 200 1900 1920 1940 Year 1960 1980 Prompting the US Surgeon General to say to the US Congress - 1967… 1967 The war against Infectious Disease has been won... Willi William H. H Stewart St t We should focus on other areas of research & public health... ● He was being overly optimistic… “It is time to close the book on infectious diseases and shift all national attention and dollars to the ‘New New Dimensions’ Dimensions of health: chronic diseases” Death from all infectious diseases USA (after the Surgeon General in 1967...) 1967 ) 1000 80 800 Mortality per 100,000 per year 60 40 600 20 400 1970 1980 1990 200 1900 1920 1940 1960 1980 Year source: Centers for Disease Control Causes of death due to bacterial di disease worldwide ld id (2002) ● Total = @ 8 million people per year 500 people will die during my lecture... “Other bacterial causes” Diarrhoeal 22% is 1.8 million deaths per year… Two-thirds are children 22% 47% 20% TB Lower Respiratory Tract Diarrhoeal Disease ● Biggest cause of infant mortality worldwide Why is infectious disease-related mortality no longer decreasing? ● Increased antibiotic resistance Some treatments no longer work ● New disease “emerging infections” Rise of antibiotic resistance in bacteria... bacteria Multiple antibiotic resistance in S. Typhimurium DT104 Humans,, England g and Wales 1981 – 2000 4500 4000 3500 sensitive ACSSuT ACSSuTTm 3000 2500 ACSSuTCp SSu others 2000 1500 1000 500 0 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 Why has antibiotic resistance occurred? ● Pressure on doctors, doctors by patients patients, to prescribe antibiotics even when they are not needed. ● Patients being prescribed antibiotics without the doctor knowing the cause of the infection. infection MRSA ● Use of antibiotics in animals for growth promotion & prophylaxis Antibiotics enter the human food chain. Human cases of S. Typhimurium DT104 Rtype ACSSuT, England 1999 & 2000 120 100 Outbreak identified 1999 2000 80 60 40 20 0 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 Week of isolation 33 35 37 39 41 43 45 47 49 51 Multiple drug resistance, S. Typhimurium DT104. H Humans, England E l d and dW Wales l 1990 – 2001 2500 2000 ACSSuT ACSSuTTm 1500 ACSSuTCp Licensing of enrofloxacin for veterinary use 1000 500 Quinolone-resistance 0 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 Percent off isolate es Quinolone-resistant Salmonella Typhimurium DT104 (UK) 18 16 14 12 10 8 6 4 2 0 Nov 93 – Enrofloxacin licensed for animal use 92 93 94 Chickens Cattle 95 Pigs 96 Humans 97 The Need for New Antibiotics ● Infectious disease is the second major cause of death in the US, US and third worldwide ● Infectious disease mortality 1900 - 1980: declined 20-fold 1980 - 1995: increased two-fold ● Pathogen acquisition of multi-drug resistance is a major contributor to death from f infectious f disease ● A d then And th there th is i the th spectre t off bio-terrorism…… bi t i Millennium Bugs-Emerging and Re-emerging Infectious Diseases,, 1996-2006 Ebola and CCHF Influenza H5N1 Hantavirus Lassa fever Monkeypox Nipah Hendra NV-CJD Rift Valley Fever SARS CoV VEE Yellow fever West Nile Plague Brucellosis E Coli O157 Multidrug resistant Salmonella Cryptosporidiosis Leptospirosis Lyme Borreliosis Adapted from Dr. Roth WHO 2006 Emerging Infectious Diseases (1940 – 2009) ● Viruses Ebola H5N1 flu H1N1 flu SARS virus West Nile Virus ● Bacteria Plague MDR Salmonella Clostridium difficile TB ● Bioterrorism SARS Impact of air travel ● No city on earth is more than 24 hours away f from any other th ● At any one moment @ half a million people are flying in commercial aircraft worldwide SARS: The first global epidemic off the th 21st 21 t century t (2003) SARS outbreak: 8098 patients & 774 deaths. (The Independent 23.3.03) Major factor behind Emerging Infectious Diseases Pathogens g Animals Humans 2003 ● Avian H5N1 ● Outbreak began in 2003 y June 2009 ● 261 deaths by Public information in China -the do’s and dont’s for avian flu Global Map of Emerging Infectious Diseases (1940 – 2004) Jones et al., (2008) Nature 451: 990-993 Influenza virus (0.1 micrometre) ● 95% smaller than E. E coli bacterium N = Neuraminidase H = Haemagglutinin Influenza H1N1 Pandemic 2009 ● Acute, highly contagious viral infection p ● Inhaled in droplets Grows in epithelial p y tract in respiratory ● Rapidly mutations Constant changes in genetic make up Influenza H1N1 Pandemic 2009 ● Started in Mexico in Feb 2009 Outbreak Reported - 24th April 2009 Pandemic declared - 29th April p 2009 ● Rapid spread worldwide worldwide... Fortunately, not as dangerous as feared... International spread of Pandemic H1N1 (8th Nov) ● 8784 deaths in 207 countries (29 (29.11.09) 11 09) Bioterrorism ● Anthrax Bacillus anthracis ● Need for antibiotics to kill particular strains Botulinum toxin ● Used in biological weapons.. ● ...and as a temporary face-lift... Botulinum toxin can be ingested with food ● 30ng botulinum toxin can be lethal ● High fatality rate (~10% cases) ● Victims are paralysed for years... Need for long-term intensive care The dangers of canning your own vegetables! USA, 1926 Take-Home... ● Bacteria, viruses & parasites cause serious disease Decimated society prior to 20th Century ● We have had notable success against many diseases Public health measures Vaccines Antibiotics ●E Emerging i pathogens th & antibiotic tibi ti resistance i t remain serious threats for the 21st Century We are relying on the next generation of microbiologists... microbiologists ● To meet the challenge g of new pathogens p g ● To understand how new viruses & bacteria cause disease New Antibiotics New Vaccines