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Pandemics Happen Poudre Valley Hospital TAC March 21, 2006 Adrienne LeBailly, MD, MPH

Pandemics Happen Poudre Valley Hospital TAC March 21, 2006 Adrienne LeBailly, MD, MPH Director, Larimer Co. Dept of Health & Environment. Larimer County in 1918. County population about 27,000 Fort Collins population 8,700 Loveland population about 5,000. Social Environment in 1918.

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Pandemics Happen Poudre Valley Hospital TAC March 21, 2006 Adrienne LeBailly, MD, MPH

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  1. Pandemics Happen Poudre Valley Hospital TAC March 21, 2006 Adrienne LeBailly, MD, MPH Director, Larimer Co. Dept of Health & Environment

  2. Larimer County in 1918 • County population about 27,000 • Fort Collins population 8,700 • Loveland population about 5,000

  3. Social Environment in 1918 • Most residents involved in agriculture, directly or indirectly • World War I was the major news story • There was rationing of coal, fuel, food and other items needed for war effort • Red Cross was very active in community, supporting war effort

  4. Outbreak begins in military training camps • Deaths occurring in training camps in East were reported in local newspapers • Numerous Larimer County enlistees/ draftees were among the fatalities (4 from Camp Dix in 1 wk.)

  5. Spreading to Civilians • Larimer County residents were aware of growing, alarming deaths among civilians in Eastern cities • First cases in CO in Boulder; army trainees on College campus. (First cases in FC at Ag College)

  6. Flu shut down schools and businesses • Loveland schools closed on Oct. 8 • Fort Collins closed schools on Oct. 10 They would not reopen until Dec. 30

  7. Headlines from issues of Fort Collins Weekly Courier, 1918

  8. 1918 Flu killed young adults • Highest number of deaths were in people in their late teens through mid 30’s

  9. By the end of the outbreak • Overall, there were 67 deaths in Loveland in a 15 week period. • Nationwide, over 650,000 people died in the U.S. • 40-50 million people died worldwide • Overall in U.S. a 2.5% case-fatality rate

  10. One Fort Collins physician died from the Spanish Flu

  11. The 1918 Virus • The 1918 virus has been recreated by sequencing RNA fragments obtained from pathological specimens in military museums and from bodies frozen in the permafrost and reverse engineering the virus. • We can study this virus and try to understand why it was so lethal.

  12. Why are we concerned today? • Widespread and spreading prevalence of avian flu in migratory birds; broad host range • Continued outbreaks among domestic poultry • Mammalian infection (cats, pigs, etc.) often lethal • Current avian flu virus share some features of 1918 virus, and is evolving

  13. Why we are concerned…. • Sporadic human cases (181 reports to date) • Most in young and healthy • Case-fatality >50% • Rare person-to-person transmission • Sustained and rapid person-to-person transmission MAY develop, causing a PANDEMIC.

  14. Influenza Virus types • Type A: Infects humans and other animals • More severe illness • Causes regular epidemics; can cause pandemics • Type B: Infectious only to humans • Causes epidemics, but less severe illness

  15. Influenza Virus • Influenza A is subtyped by surface proteins • Hemagglutinin (H) • 16 different types • Helps virus enter cells by binding to sialic acid • Neuraminidase (N) • 9 different types • Helps virus leave cell to infect other cells

  16. Influenza Virus • All known subtypes of Influenza A found in birds - 144 (16 x 9) possible combina-tions of H’s and N’s • H5 and H7 cause severe outbreaks in birds • Human disease mostly due to H1, H2, H3 and N1 and N2. • The H and N surface proteins are the targets of antibodies

  17. Influenza Virus • The virus has 8 genetic segments made ofsingle-stranded RNA,coding for 10 genes. • The virus replicates inaccurately, leading to genetic variants that change continually.

  18. Influenza Virus • New vaccines needed yearly • Major change in H or N may leave immune system unable to recognize new virus • No immunity in population —potential for pandemic

  19. Seasonal Influenza • Outbreaks yearly, usually in winter months • Illness more severe for very young, elderly, or those with pre-existing health conditions • Yearly, 5-20% of population get the flu • Annually causes >200,000 hospitalizations in US • 36,000 influenza/pneumonia deaths yearly in US

  20. Transmission of flu virus • Incubation period of 1-4 days for regular flu - not clear if H5N1 might be longer • Can be communicable to others 24 hours before symptoms begin - and up to 5 days or more after onset (adults) or 10 or more days (children) • Usually spread through respiratory droplets or contaminated objects. May also be airborne, and perhaps thru feces.

  21. Seasonal Occurs every year Occurs during winter (usually Dec-Mar) Most recover in 1-2 weeks without tx Very young, very old, ill most at risk of serious illness Pandemic Occurs infrequently(3-4 per century) Occurs any time of year Some may not recover, even with tx People of all ages may be at risk Seasonal Flu vs Pandemic Flu

  22. Avian Outbreaks Human Pandemics

  23. Over the past 500 years • Three to four pandemics have occurred per century, although there is no specific periodicity. • The longest period of time between pandemics is 42 years. • As of 2006, it’s been 38 years since the last influenza pandemic.

  24. Two Ways Flu Viruses Change • Point mutations occur in viral RNA during replication (sometimes called Antigenic Drift) • Reassortment - genetic segments from two different flu viruses infecting the same cell swap genetic segments (sometimes called Antigenic Drift)

  25. N Engl J Med 2005; 353:2210

  26. N Engl J Med 2005; 353:2210

  27. N Engl J Med 2005; 353:2210

  28. N Engl J Med 2005; 353:2210

  29. How are bird & human influenza viruses different? • The hemagglutinins (H) of bird vs. human viruses preferentially attach to different forms of sialic acid.

  30. Transmissibility vs. Virulence • Hemagglutinins (H) probably play a major role in the ability of a virus to infect and be transmitted between humans. • Hemagglutinins may be related to virulence, but other viral genes are probably involved as well.

  31. There are severe pandemics and mild pandemics

  32. Infectious Disease Deaths 1900’s Deaths per 100,000 per year United States, 1900-1996 1957 1968 1918 JAMA.1999; 281: 61-66.

  33. Why did young people die in 1918? • Over-reaction by the immune system called “cytokine storm” • Those with the strongest immune systems affected • Older people and youngest often die of bacterial pneumonia complicating flu -- treatable now with antibiotics • Even in 2006, no good treatment for “cytokine storm.”

  34. H5N1 Avian Influenza • Hong Kong 1997 • 18 human cases, 6 deaths • 1.4 million birds destroyed • Reappeared in Asia in 2003 • Human cases in Hong Kong family that had traveled to China in February • Outbreaks in birds go undetected/unreported • Tigers and leopard infected in Thailand

  35. East Asia & Pacific: Cambodia, China, Hong Kong, Indonesia, Japan, Laos, Malaysia, Mongolia, Burma, Thailand, Vietnam South Asia: India, Pakistan (H5), Kazakhstan Africa: Cameroon, Niger, Nigeria Middle East: Egypt, Iran, Iraq, Israel, Turkey Europe & Eurasia: Afghanistan,Albania, Austria, Azerbaijan, Bosnia & Herzegovina (H5), Bulgaria, Croatia, Denmark (H5), France, Georgia, (H5), Germany, Greece, Hungary, Italy, Poland, Romania, Russia, Serbia & Montenegro (H5), Slovak Republic, Slovenia, Sweden Switzerland, Ukraine Countries with H5N1 (as of 3/18/06)

  36. Concern with H5N1 Influenza • Virus mutates rapidly • Can acquire genes from viruses infecting other species • H5N1 has acquired some of genetic changes in the 1918 virus associated with human-human transmission • Causes severe disease in humans • High fatality rate

  37. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO as of March 16, 2006

  38. Influenza vaccines and treatment

  39. Inactivated trivalent vaccine (killed vaccine) 2 A, 1 B Effectiveness of vaccine depends on “match” between circulating strains and those in vaccine Yearly Vaccine Development 2005–2006 Influenza Season A/New Caledonia/20/99-like A/California/7/2004-like (H1N1) (H3N2) InfluenzaProtection B/Shanghai/361/2002-like

  40. Prior Year January February March April Surveillance on circulating strains Selection of specific strains Preparation and distribution of virus stock to manufacturers Seed pools inoculated into eggs N Engl J Med 351:20 November 11, 2004

  41. May June July August September October Harvest and concentration of fluids Vaccine inactivated and purified Vaccine blended, content verified Packaging, labeling, delivery N Engl J Med 351:20 November 11, 2004

  42. Influenza—Vaccine Production • Flu vaccines first produced in 1940s • 2 manufacturers in US for flu vaccine • 80 million doses produced by late September (about 60 M made in US) • 6-9 months to produce vaccine

  43. Pandemic Vaccine • Inactivated pandemic vaccine would likely require 2 doses a month apart to provide full protection • U.S. doesn’t have the capacity to manufacture 600 million doses to cover the U.S. population (currently about 60 million)

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