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ABSTRACT: For decades, public health officials have been concerned about the reoccurrence of pandemic influenza. The wor

ABSTRACT: For decades, public health officials have been concerned about the reoccurrence of pandemic influenza. The worst documented pandemic occurred in 1918-1919, killing an estimated 20-40 million people worldwide. Although influenza has not wreaked such havoc since then,

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ABSTRACT: For decades, public health officials have been concerned about the reoccurrence of pandemic influenza. The wor

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  1. ABSTRACT: For decades, public health officials have been concerned about the reoccurrence of pandemic influenza. The worst documented pandemic occurred in 1918-1919, killing an estimated 20-40 million people worldwide. Although influenza has not wreaked such havoc since then, there have been close calls -- most recently with the avian influenza strain currently circulating in SE Asian poultry flocks. In the meantime, new threats have emerged. SARS has been the most widespread of these, and has carried a high human and economic toll where it has struck. Will one of these new diseases take the place of the dreaded influenza?

  2. The New Flu?Pandemic Influenza,Avian Flu, and SARS Amy D. Sullivan, Ph.D, MPH Epidemiologist Multnomah County Health Department

  3. Then Now

  4. Topics for This Evening… • Review the Pandemic Flu of 1918-1919 • Was it really that bad? (Hint: Yes) • How could it have happened? • Subsequent threats • Avian flu • SARS • Discuss: Is another event like pandemic flu inevitable?

  5. What Was So Striking… • Characteristic symptoms & outcomes • High global death tolls • Large numbers of deaths among healthy adults • So completely ignored for so long

  6. Characteristic Symptoms and Outcomes • “…dusky heliotrope cyanosis of the face, lips, and ears… [and] purulent bronchitis with bronchopneumonia” (Oxford, 2001) • Case fatality proportion 25-50%

  7. The Death Toll • Global estimates • 1920’s: ~21.5 million dead • India alone: 18 million • 1998 conference: 50-100 million • Varied greatly by country & region • Europe & N. America: 3-20deaths/1,000 • Africa: 20-445deaths/1,000 people • Asia/Pacific: 3-220deaths/1,000 people

  8. Oct-Nov 1918 (second wave)

  9. Deaths Among Healthy Adults • Influenza deaths usually among youngest & oldest • Rates during 1918 • Infants & over 40 ~2-10-fold higher • 10-20 yrs old: 20-100-fold higher • 20-30 yrs old 20-180-fold higher

  10. Multnomah County Deaths (3 month period; Total deaths ~20,200)

  11. Was Pandemic Flu Really That Bad? • Yes… In thinking about the potential of Avian flu (or other emerging respiratory illnesses) to wreak havoc, useful to understand…

  12. How Could Such a Catastrophic Event Occur? • Biologic factors • Segmented genome of the influenza virus • Unique to influenza viruses? • Epidemiologic Factors • Route of transmission • Population movements/migrations • “Seeding” the population

  13. The Influenza A Virus • Typically spherical • 50-120 nm diameter • Single-stranded RNA virus • Genome in 8 segments • Encode key surface glycoproteins • Haemagglutinin (HA) • Neuraminidase (NA)

  14. The Segmented Genome At Work Role of HA in cell infection Genome segments can exist inside host cell “naked & free”

  15. Flu Haemaglutinin • 15 subtypes identified allow for… • Variability in human infection • H1, H2, & H3 pandemic potential • H5 poor human-human spread • H7 birds not humans • Different possible host species • H1: birds, pigs, & people • H5: birds & people

  16. Shift vs. Drift • Influenza viruses change regularly • Usually “antigenic drift” • “Normal” mutations • Changes in surface glycoprotiens but can cross-react with existing immunity • Sometimes “antigenic shift” • Segments can rearrange when co-infecting same cell • Reassortments by very different strains can profoundly change ability to recognize

  17. “Spanish Flu” & Antigenic Shift • H1N1 subtype of Influenza A • H1 from an antigenic shift • Avian origin? Avian via swine? • Poor population-level immunity key in devastation • Virulence factors not ruled out

  18. Influenza Virulence • Infects respiratory tract epithelial cells • Ciliated & serous; not basal • Upper respiratory infection less severe then infection in lungs • Mutation(s) affecting speed or invasiveness of infection? • Affect mortality • And transmission?

  19. Infection & Transmission • 15-60% of infected people develop symptoms • Incubation period: 1-3 days • Infectious period: 3-7 days after symptom onset • Symptomatic most likely to transmit • Mode of transmission: • Fomite possible • Droplet or aerosol

  20. Droplet vs. Aerosolized Spread • Droplet transmission • Respiratory secretions >5mm • Fall out of air quickly with ~3 feet • Easier to protect against? • Aerosolized transmission • Respiratory secretions <5mm • Can stay airborne for hours • Both can occur for any one disease

  21. Population Mixing an the Spread of Spanish Flu • 1918-19 a time of great social upheaval • 1914: Great Britain declares war on Germany • 1917: U.S. joins WWI • 1918: U.S. troops arriving in Europe; Armistice signed at end of year • 1919: Armies head home • Airplanes not a factor, but huge movements of people in the world

  22. “Seeding” the Population • First appearance in 1918? • First described in Fort Riley, Kansas in March 1918 • “…near simultaneous appearance [of flu] in March-April 1918 in North America, Europe, and Asia…” (Taubenberger, 2001) • Pandemic flu strain likely existed before 1918 (but not for long)

  23. Etaples, France. 1916 • WWI British Army base • Crowded conditions: animals & people • People from all over the Empire • Outbreak of “Purulent Bronchitis” • Dec 1916 thru spring 1917 • Case fatality ~45% • Bacillus influenza (a.k.a. Haemophilis influenza) in 18 of 20 cases • Earliest documented report

  24. How Could Such a Catastrophic Event Occur? • Biologic factors • High infectivity with novel “look” (immunologically) • Analogous to zoonotic disease but better adapted • Epidemiologic Factors • Droplet & aerosolized transmission • Occurred at a time of global migration • Was able to “seed” itself around the globe

  25. Avian Influenza H5N1 • Hong Kong, 1997 • 18 people hospitalized; 6 die • Hundreds likely ill • Young adults affected • Infection directly from chickens • Most avian flu viruses do not directly infect humans • No person-to-person transmission

  26. Avian Flu in 2003-4 • December 2003 H5N1 avian flu identified in Vietnam • By March 10th, 2004 • 33 cases with 22 deaths in Vietnam and Thailand • Infected birds in 8 Asian countries • Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand, and Vietnam • Investigation of person-person transmission in Vietnam case

  27. Could a Catastrophic Event Occur? • Biologic factors • High infectivity with novel “look” (immunologically) • Epidemiologic Factors • Droplet & aerosolized transmission – Rare for person-to-person • Occurred at a time of global migration • Was able to “seed” itself around the globe - NO

  28. Severe Acute Respiratory Syndrome (SARS) • Pneumonia caused by a coronavirus • Fatal pneumonia • Fever (>100.4 F or 38 C); Dry cough, shortness of breath, difficulty breathing • Tx: Supportive therapy only • Incubation period, ~6 days • Case fatality proportion, 5-15% • Much higher in persons over 60 years

  29. Discovering SARS • First recognized in Viet Nam, February 2003 • Businessman traveled from Guangdong • Hospital outbreak among persons exposed to him • Occurred in Guangdong Province as early as November 2002

  30. Where Is SARS From • Don’t know for sure • In Guangdong Province market • Identified in exotic animals sold for food • Seropositive asymptomatic individuals among sellers • Circulating before this outbreak?

  31. How is SARS Spread? • Droplet? • Close contact appears important • Household contacts • Healthcare workers • But… many unanswered questions • Aerosol pattern in some cases • “Superspreaders” • Still unsure about… • Fomite transmission • Asymptomatic transmission

  32. Amoy Gardens, Hong Kong Aerosolized virus from improperly ventilated U-traps spread up outside ventilation shaft in an apartment building

  33. SARS Cases Reported to WHO as of June 13, 2003 8,445 cases; 790 deaths t t t t t t t t t t t t t t t t t t t t t t t t t t t t t t t

  34. Current SARS Situation • Chinese outbreak from apparent infection in a research lab • 8 cases (confirmed and suspected) • All cases epidemiologically linked • ~1,000 contacts under surveillance • 640 in Beijing; 353 in Anhui Provence • Virology Institute closed

  35. Could a Catastrophic Event Occur? • Biologic factors • High infectivity with novel “look” (immunologically) • Epidemiologic Factors • Droplet & aerosolized transmission – Rare for person-to-person • Occurred at a time of global migration • Was able to “seed” itself around the globe - NO

  36. Discuss Is another event like pandemic flu inevitable?

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