Bio303 Lecture Three: New Foes, Emerging Infections

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New foes. In this lecture I will describe emerging infections, their epidemiology and ecology and the threats that they pose. I will focus on three case studies: SARS, pandemic flu (with help from Jennifer Gardy) and the German STEC outbreak of May-June 2011

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Bio303 Lecture Three: New Foes, Emerging Infections

  1. 1. Global Health and Emerging Infections 3: New Foes Professor Mark Pallen Bio303
  2. 2. Global Health and Emerging Infections1. The Global Burden of Infection and an Old Enemy, Malaria. In this lecture I will survey the global burden of infection, including its human and economic costs, and examine the problem of neglected tropical diseases before focusing on one of the most serious infectious threats to humanity: malaria, outlining its evolutionary origins, impact on human health and wealth and the steps taken to control and treat this infection.2. Two Old Enemies, TB and Leprosy. In this lecture I will focusing on another of the most serious infectious threats to humanity, tuberculosis, outlining its evolutionary origins, impact on human health and wealth and the steps taken to control and treat this infection. I will also discuss a related mycobacterial infection, leprosy and recent progress in its control.3. New foes. In this lecture I will describe emerging infections, their epidemiology and ecology and the threats that they pose. I will focus on three case studies: SARS, pandemic flu and the German STEC outbreak of May-June 20114. Operation Eradication. In this lecture, I will celebrate the global eradication of smallpox, from the campaigns beginnings in Gloucestershire to the last tragic cases here in Birmingham. I will discuss what is required for an infectious disease to be eradicated and summarise progress on disease eradication, focusing on poliomyelitis and guinea worm.5. Lab Diagnosis of Infectious Disease. Here I will provide an overview of how infections are diagnosed in the clinical microbiology lab, focusing not just on technologies, old and new, but on practical issues and workflows crucial to optimal use of the lab.
  3. 3. Emerging Infectious Diseases (EIDs) diseases caused by newly identified species/strain  e.g. SARS, AIDS, Ebola, Nipah, E. coli O104:H4 new infections resulting from variant of existing organism  e.g. pandemic influenza known infection spreads to new region or population  e.g. West Nile virus re-emerging infections due to drug resistance or breakdowns in public health  e.g. tuberculosis, cholera For a full list see http://www.nature.com.ezproxyd.bham.ac.uk/nature/journal/v451/n7181/extref/nature06536-s1.pdf
  4. 4. Emergence Factors Human demographics and behaviour (e.g. air travel) Changing human susceptibility (e.g. with AIDS, cytotoxics) Climate change Economic development and land use Microbial adaptation and change Breakdown of public health measures Abnormal natural occurrences War, bioterrorism
  5. 5. SARS: First pandemic ofnew millennium Nov 2002  Initial cases in southern China  Chinese authorities slow in reporting problems; PRC later apologises By Feb 2003  Outbreak in Guangzhou hospitals involving patients and health care workers.  Cumulative 305 cases (105 in health care workers) & 5 deaths from unknown acute respiratory syndrome
  6. 6. SARS: history of the epidemic 15 Feb: 65-yr-old professorof nephrology from Guangdong falls unwell 21 Feb: resides at “hotel M”, Metropole Hotel in Kowloon, HK Infects 17 residents at hotel 22 Feb: admitted to hospital CC BY-SA 2.0 John Seb http://www.flickr.com/photos/johnseb/164756503/sizes/z/in/photostrea
  7. 7. SARS: history of the epidemic Hotel M contacts travel to Hanoi, Singapore and Toronto, starting new outbreaks  26 Feb: US businessman Johnny Chen (hotel M contact) falls ill on flight to Singapore; admitted to hospital in Hanoi, dies  4 Mar: another Hotel M contact starts HK hospital outbreak  5 Mar: another Hotel M contact dies in Toronto, five family members affected
  8. 8. SARS: history of the epidemic Carlo Urbani, Italian doctor and WHO physician in Hanoi notifies WHO of explosive nosocomial outbreakin Hanoi Urbanis descriptionof casesoutside Guangdong alerts healthauthorities throughout world and accelerates research to identify virus and combat disease, saving 1000s of lives Urbani dies on March 29, a month after seeing his first case and 18 days after falling ill on a plane to Bangkok "If I cannot work in such situations, what am I here for - answering e-mails, going to cocktail parties, and pushing paper?" Dr. Carlo Urbani, 2003
  9. 9. SARS: history of the epidemic 12-15 Mar 2003  WHO issues global alert  coins name “sudden acute respiratory syndrome”  calls for global collaborative research effort 21 March  HK Scientists isolate new coronavirus from open lung biopsy; soon confirmed in US and Germany 12 April  genome sequence shows this virus is distinct from all known human pathogens
  10. 10. SARS: history of the epidemic Jun 2003: virus almost identical to SARS- CoV isolated from palm civets and other game food mammals 5 Jul 2003: Lack of transmission in Taiwan signals end of human-to-human transmission 3 Sep 2003: Lab-acquired SARS-CoV infection in Singapore Dec 2003/Jan 2004: five cases from new animal-to-human transmission in Guangzhou 17 Dec 2003: Lab-acquired SARS-CoV infection in Taiwan 25 Mar & 17 Apr 2004: Lab-acquired infection in Beijing, with secondary and tertiary spread 16 Sep 2005: SARS-CoV-like virus in horseshoe bats
  11. 11. Local transmission in Toronto,Ottawa, San Francisco, UlanBator, Manila, Singapore, Taiwan,Hanoi and Hong KongWithin PRC spread to Guangdong,Jilin, Hebei, Hubei, Shaanxi,Jiangsu, Shanxi, Tianjin and InnerMongolia
  12. 12. SARS-CoV Coronavirus  S protein binds host receptor  Previously thought to be benign angiotensin-converting enzyme group; 15% of all cases of 2 (ACE2) common cold  Mutations in S protein reveal large, enveloped, +ssRNA virus evolution of virus as epidemic Irregular shape, club-shaped progresses spikes  Adaptive changes show Genome encodes increase affinity for human  replicase (Orf1ab) ACE2  structural proteins: spike [S],  Neutral changes reveal envelope [E], membrane [M], phylogeny of HK outbreak nucleocapsid [N]
  13. 13. SARS Case Definition and Clinical Findings Incubation period of SARS 2-14 days Clinical history & observation  flu-like symptoms : fever >38°C, myalgia, lethargy, GI symptoms, cough, sore throat, shortness of breath ≤10 days before onset of symptoms  Close contact with probable/suspected SARS patient OR  Been in area with transmission of SARS Chest radiography: important role  70-80% patients have abnormal chest radiographs Now "laboratory-confirmed SARS” possible
  14. 14. Transmission of SARS-CoV Human-to-human transmission  direct or indirect contact of the mucosae with infectiousrespiratory droplets or fomites  Higher environmentalstability than other human coronaviruses  2-3 days on dry surfaces; 2-4 days in stool Explosive outbreak affecting 100s in Amoy Garden housing estate in HK due to  dried U traps in sewage drains  exhaust fans generate aerosols in toilets  aerosols ascend light well connecting different floors SARS transmitted in commercial aircraft on five flights
  15. 15. Origins of SARS-CoV Highly probable: origination is a cross-species jump from civets and/or horseshoe bats to humans Second case was chef with multiple animal contact Phylogeny from helicase sequences
  16. 16. Controlling SARS Principle: to break the chain of transmission from infected to healthy person 3-step protocol of disease confinement  Case definition and detection  Prompt isolation  Contract tracing  Daily health check  Voluntary home isolation Treatment  interferon alfacon-1 with steroids  protease inhibitors with ribavirin  convalescent plasma containing neutralizing antibody
  17. 17. Epidemic Containment Creation of emergency operating center Institutional support  Efficient quarantine measures  1000s quarantined in HK, Canada, SG, Taiwan  Schools closed in HK, SG  Legislation International collaboration—WHO  Travel alerts and restrictions  controversially WHO advised only essential visits to Toronto  Airline passengers screened for fever using thermal imaging scans  Coordination for research  Agreement of countries on containment protocol
  18. 18. SARS epidemic: the aftermath SARS epidemic involved 37  rapid global dissemination countries around the world depended on 8,096 cases and 774 deaths  capacity for human-to-human  Case-fatality rate ~10% transmission  50% for >65 yrs old  the lackof awareness in hospital infection control Causes of epidemic  internationalair travel  rapid economic growth inChina primed demand for exotic food  unparalleled dramatic impact on animals such as civets health care systems,economies, and societies of affected countries  overcrowdedcages with no biosecurity in wet markets  ability of virus to jump from animals to human
  19. 19. SARS next time: are we ready? SARS could return if conditions  gaps still exist in are fit for the  understanding transmissibility and introduction,mutation, pathogenesis in humans amplification, and transmission  screening tests of this dangerousvirus  foolproof infection control  animal reservoir persists in  effective antivirals and civets, bats etc immunomodulatory agents  safe effective vaccine BUT next time, we will have  identifying immediate animal host wherewithal to diagnose and that transmitted the virus to caged respond civets  And treat and vaccinate? 4,000 publications available online
  20. 20. Swine Flu 2009: the first open-source epidemic?
  21. 21. Haemolytic-uraemic syndrome Shiga-toxin-producing E. coli (STEC)  bloody diarrhoea; damage to kidneys and brain  anaemia; loss of platelets
  22. 22. German E. coli O104:H4 outbreak May-July 2011 >4000 cases >40 deaths Link to sprouting seeds High risk of haemolytic- uraemic syndrome Females particularly at risk
  23. 23. “Calling International Rescue…”Herr Doktor Holger RohdeUKE Universitätsklinikum Hamburg-Eppendorf
  24. 24. “Calling International Rescue…”
  25. 25. UKE Hamburg BGI-Shenzhen
  26. 26. Ion Torrent Millions of wells reading sequences Microchip detects release of protons ~3 hour run-time ~£500 cost per run
  27. 27. Crowd-sourcing the genome
  28. 28. Crowd-sourcing the genome Within 24 hours of its release, the genome is assembled Within two days, assigned to an existing lineage Within five days, strain-specific diagnostic test released Within a week, two-dozen reports on the biology and evolution of the strain had been filed on an open- source wiki
  29. 29. Crowd-sourcing the genome
  30. 30. Take away messages Pathogens don’t bother with passports!  Not a new strain  something similar seen in Germany ten years ago and in Korea  closest genome-sequenced strain was isolated from Central African Republic in late 1990s German STEC comes from a lineage circulating in human populations rather than from an animal source
  31. 31. Take away messages Bacteria evolve quickly  Virulence factors in E. coli can jump from one lineage to another on bacterial viruses  Antibiotic resistance seen where no obvious prior use of antibiotics Infection still presents a threat even in the most advanced societies
  32. 32. Take away messages Open-source genomics: propitious confluence of  high-throughput genomics  crowd-sourced analyses  a liberal approach to data release Social media (e.g. blogging, Twitter) can augment usual channels of academic discourse But have we broken the mould?  appropriate for public heath emergencies…  …but not for “ordinary science”? Cite or site?
  33. 33. Open-source genomics Genome sequencing brings the advantages of  open-endedness (revealing the “unknown unknowns”),  universal applicability  ultimate in resolution Bench-top sequencing platforms now generate data sufficiently quickly and cheaply to have an impact on real-world clinical and epidemiological problems
  34. 34. Addendum: Jennifer Gardy’s slides http://creativecommons.org/licenses/by-sa/2.0/ Attribution-ShareAlike 2.0 Generic (CC BY-SA 2.0) http://www.youtube.com/watch?v=LmAugMSJ1-Y
  35. 35. public health inthe 21st century:the open sourceoutbreakdr. jennifergardybc centre for disease controlgenome research laboratory
  36. 36. new technology
  37. 37. new attitudes
  38. 38. public health 2.0
  39. 39. www.globecampus.ca/blogs/nerd-girl
  40. 40. open source outbreak
  41. 41. take-home pointtechnological advances shift in scientists’ attitudespublic health 2.0: rapid & collaborative
  42. 42. rewind to march 2009
  43. 43. CDC California WHOincreased flu activity inMexico pandemic!
  44. 44. 5,000 confirmed cases100-150,000 possiblecases at June 11, 2009
  45. 45. open source outbreak
  46. 46. sharing germs,sharing data
  47. 47. CDC California WHOincreased flu activity in april 25: 1st genomeMexico pandemic!
  48. 48. april 26: international wiki13 people, 8 institutes, 4 countrieshttp://tree.bio.ed.ac.uk/groups/influenza
  49. 49. april 26: origins of the virus calculated
  50. 50. april 30: origins data published5 days from sequenceto open-access paper
  51. 51. CDC California WHOincreased flu activity in april 25: 1st genomeMexico may 6: 69 virus’ RNA pandemic!
  52. 52. virus entered human population late08/early 09
  53. 53. may 5: first major paper submittedmay 11: first major paper published
  54. 54. CDC California WHOincreased flu activity in april 25: 1st genomeMexico may 6: 69 virus’ RNA june 11: 250+ papers pandemic!
  55. 55. SARS, 2003 day 19day 0 virus one viralisolation genome day 19 H1N1, 2009day 0 virusisolation 100+ viral genomes where/when it arose multiple papers vaccine seed strain
  56. 56. technological advancesshift in scientists’ attitudes
  57. 57. genomes = easy, cheap, fast
  58. 58. human genome project(1990)10 years to draft3 more to complete$3 billion100s of people
  59. 59. spring 2009 four weeks $48,000 worth of reagents stephen quake, stanfordthree-person team bioengineering
  60. 60. data = easy, cheap, fast
  61. 61. the file-sharing generation from flickr user amy and cas
  62. 62. 85% ofscientists support open Mann et al, Comm. of the ACM 52(3):135. (2009
  63. 63. collaboration
  64. 64. what about H1N1?susceptible to antiviralsnot drifted from vaccine straindisplaced seasonal influenzarace between the spread ofthe virus and the spreadof information
  65. 65. what aboutthe nextbug?
  66. 66. genomesurveillance
  67. 67. population sampling to pickup threats before the lab orclinic
  68. 68. months of undiscovered circulation inpeople
  69. 69. sewage-nomicsfrom flickr user stuck incustoms
  70. 70. embrace newtechnologies
  71. 71. embrace open accessand collaboration
  72. 72. don’tembraceanyone witha feverand/or cough from flickr user jess and coli
  73. 73. oink! oink!(thank you)
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