1. Bureau of Emergency Preparedness and Response 88 Years of Influenza Pandemics in 15 Minutes Peter C. Kelly, M.D. Arizona Dept. of Health Services

2. Bureau of Emergency Preparedness and Response Pandemic Influenza: history and background Peter C. Kelly, M.D., FACP Arizona Dept. of Health Services

3. Bureau of Emergency Preparedness and Response Drivers for Pan Flu Preparedness WHO Influenza Preparedness WHO Influenza Preparedness SARS and Toronto SARS and Toronto Hurricane Katrina and New Orleans Hurricane Katrina and New Orleans

4. Bureau of Emergency Preparedness and Response It’s all about the virus

5. Bureau of Emergency Preparedness and Response Influenza Virus RNA, 8 segments RNA, 8 segments Unstable,mutates frequently Unstable,mutates frequently Surface proteins Surface proteins HemagglutininHemagglutinin NeuraminidaseNeuraminidase Niche in nature is birds Niche in nature is birds

6. Bureau of Emergency Preparedness and Response Drift and Shift Both refer to genetic changes Both refer to genetic changes Drift: Minor changes in H and N antigens; occur annually or every few years Drift: Minor changes in H and N antigens; occur annually or every few years Shift: Major change (30% or more) in H and/or N antigens; “new” virus. Important for starting pandemics Shift: Major change (30% or more) in H and/or N antigens; “new” virus. Important for starting pandemics

7. Bureau of Emergency Preparedness and Response Influenza is Global

8. Bureau of Emergency Preparedness and Response Surface Glycoproteins Used to classify virus; H1, H2 etc Used to classify virus; H1, H2 etc Important in disease Important in disease HA attaches virus to respiratory epithelial cellsHA attaches virus to respiratory epithelial cells NA facilitates release of virus from infected cellNA facilitates release of virus from infected cell Immunity/vaccines Immunity/vaccines

9. Bureau of Emergency Preparedness and Response Influenza Virus and Birds Migratory waterfowl Migratory waterfowl Often not diseased Often not diseased Transmit to domestic birds and other animals Transmit to domestic birds and other animals 15 H types, 9 N types 15 H types, 9 N types Only 3 H,2 N in humans Pathogenicity varies Pathogenicity varies

10. Bureau of Emergency Preparedness and Response How does the virus get to humans?

11. Bureau of Emergency Preparedness and Response How does the virus get from person to person?

12. Bureau of Emergency Preparedness and Response How does the virus cause disease? Attaches to respiratory epithelium Attaches to respiratory epithelium Enters the cell and reproduces Enters the cell and reproduces Causes cell death Causes cell death Primary target is bronchial tissue Primary target is bronchial tissue

13. Bureau of Emergency Preparedness and Response Pandemics

14. Required for Influenza Pandemic “New” virus (antigenic shift) “New” virus (antigenic shift) Susceptible populationSusceptible population Transmitted from animals to humans Transmitted from animals to humans Cause disease in humans Cause disease in humans Efficient person to person transmission Efficient person to person transmission

15. Bureau of Emergency Preparedness and Response Influenza Pandemics Have occurred for centuries Have occurred for centuries Occur 11 to 42 years apart Occur 11 to 42 years apart Unpredictable but not randomUnpredictable but not random Attack rates of 10 to 40% Attack rates of 10 to 40% Excess mortality Excess mortality But humanity survives But humanity survives

16. Bureau of Emergency Preparedness and Response 20 th Century

17. Bureau of Emergency Preparedness and Response Current Model of Pandemics

18. Bureau of Emergency Preparedness and Response 1918-19 Pandemic aka Spanish Flu aka Spanish Flu H1N1 virus, H1N1 virus, Genetics: “avian like” Genetics: “avian like” First cases in USA First cases in USA Global spread ~1 yr Global spread ~1 yr Mortality 20-50 million Mortality 20-50 million USA 500,000 USA 500,000

19. Bureau of Emergency Preparedness and Response Impact High mortality High mortality Social disruption Social disruption BurialBurial Public servicesPublic services Events cancelledEvents cancelled Spread along troop transport routes Spread along troop transport routes Poor public health response Poor public health response

20. Bureau of Emergency Preparedness and Response Mortality and “Waves” Taubenberger, Morens. EID. 2006;12: 15-22.

21. Bureau of Emergency Preparedness and Response “the Mother of All Pandemics” Taubenberger, Morens.EID.2006;12:15-22 H1N1 1918 virus is the ancestor of current influenza viruses H1N1 1918 virus is the ancestor of current influenza viruses Human and porcine lineage have some H1N1 genes Human and porcine lineage have some H1N1 genes H3N2 virus retains some H1N1 genes H3N2 virus retains some H1N1 genes None of these as virulent as original None of these as virulent as original

22. Bureau of Emergency Preparedness and Response 20 th Century

23. Bureau of Emergency Preparedness and Response 1957-58 Influenza Pandemic Asian Influenza H2N2 virus: 3 new genes (H,N, PB1); 5 genes from 1918 H1N1 H2N2 virus: 3 new genes (H,N, PB1); 5 genes from 1918 H1N1 First cases in China First cases in China Spread around world in 6 months Spread around world in 6 months 1 st wave: Fall’57 school age 1 st wave: Fall’57 school age 2 nd wave: Jan’58 adults 2 nd wave: Jan’58 adults 80,000 deaths in USA 80,000 deaths in USA Very young and elderlyVery young and elderly

24. Bureau of Emergency Preparedness and Response 20 th Century

25. Bureau of Emergency Preparedness and Response 1968-69 Influenza Pandemic Hong Kong Influenza H3N2 Virus, 2 new genes(H, PB1), 5 retained from 1918. N2 from Asian H3N2 Virus, 2 new genes(H, PB1), 5 retained from 1918. N2 from Asian Only 1 antigen shifted Only 1 antigen shifted Population has some immunity to N2 Population has some immunity to N2

26. Bureau of Emergency Preparedness and Response H3N2 Influenza Lowest mortality of 20 th cent. pandemics Lowest mortality of 20 th cent. pandemics 34,000 deaths in USA34,000 deaths in USA U shaped mortality curve U shaped mortality curve

27. Bureau of Emergency Preparedness and Response Wave Phenomenon

28. Bureau of Emergency Preparedness and Response Where are we now? H3N2 era. Seasonal influenza. Antigenic drift. Annual vaccine. Mortality ~36,000 H3N2 era. Seasonal influenza. Antigenic drift. Annual vaccine. Mortality ~36,000 SURPRISE SURPRISE 2003 H5 N1 avian virus 2003 H5 N1 avian virus Highly pathogenic in birds, especially chickens Highly pathogenic in birds, especially chickens Almost world wide spread (asia,africa,and europe) Almost world wide spread (asia,africa,and europe)

29. Bureau of Emergency Preparedness and Response

32. Humans and H5N1 HPAI Few cases in close contact with chickens Few cases in close contact with chickens As of 7/14/06; 230 cases and 132 deathsAs of 7/14/06; 230 cases and 132 deaths No efficient human to human transmission No efficient human to human transmission

33. Bureau of Emergency Preparedness and Response Required for Influenza Pandemic “New” virus (antigenic shift) “New” virus (antigenic shift) Susceptible populationSusceptible population Transmitted from animals to humans Transmitted from animals to humans Cause disease in humans Cause disease in humans Efficient person to person transmission Efficient person to person transmission

34. Bureau of Emergency Preparedness and Response WHO Alert

35. Bureau of Emergency Preparedness and Response International Preparedness Control in birds Control in birds Global Influenza Surveillance Global Influenza Surveillance Vaccine development Vaccine development Antiviral drugs, oseltamivir Antiviral drugs, oseltamivir National preparedness plans National preparedness plans

36. Bureau of Emergency Preparedness and Response Be an optimist! Power of scientific inquiry Power of scientific inquiry WHO global surveillance is good and getting better WHO global surveillance is good and getting better Communication and cooperation among nations is better since SARS Communication and cooperation among nations is better since SARS Vaccine development and production methods are on a fast track Vaccine development and production methods are on a fast track

37. Bureau of Emergency Preparedness and Response What about state and local PH?