Pandemic Influenza

1. Pandemic Influenza CAPT Lynn Slepski, RN, MSN, CCNS Senior Public Health Advisor Immediate of the Assistant Secretary Infrastructure Protection

2. Objectives Define Pandemic Define Avian Flu Contrast normal flu vs. pandemic flu Explore the current Avian Flu issue Answer your questions

3. Background: Influenza Contagious respiratory disease caused by the influenza virus Occurs both in birds and mammals Typically remains specific to the species in which they occur

4. Background: Influenza Virus A globular particle (about 100 nm in diameter)�smallest unit of �life� Cannot �move� or replicate on its own Sheathed in a lipid bilayer (derived from the plasma membrane of its host) 8 RNA Molecules HA genes (Hemagglutinin) NA genes (Neuramidase) NP (Nucleoproteins) Variety of matrix, proteins, and polymerases 16 HA and 9 NA subtypes with 144 combinations possible They are obligate intracellular parasites. Probably there are no cells in nature that escape infection by one or more kinds of viruses. (Viruses that infect bacteria are called bacteriophages.) Outside the cell, they consist of particles called virions. Virions range in size from as small as the poliovirus shown above magnified some 450,000 times (courtesy of A. R. Taylor), which is 30 nm in diameter (about the size of a ribosome) to as large as the vaccinia virus which, at 230 nm, is larger than some bacteria. The virion consists of An outer shell, the capsid, made of protein. The capsid is responsible for protecting the contents of the core establishing what kind of cell the virion can attach to infecting that cell Some viruses contain other ingredients (e.g., lipids, carbohydrates), but these are derived from their host cells. an interior core containing the genome; either DNA or RNA The genes are few in number (3 - 100 depending on the species). They encode those proteins needed for viral reproduction that the host cell will not supply. Often, one or more proteins (enzymes) needed to start the process of reproduction within the host cell. They are obligate intracellular parasites. Probably there are no cells in nature that escape infection by one or more kinds of viruses. (Viruses that infect bacteria are called bacteriophages.) Outside the cell, they consist of particles called virions. Virions range in size from as small as the poliovirus shown above magnified some 450,000 times (courtesy of A. R. Taylor), which is 30 nm in diameter (about the size of a ribosome) to as large as the vaccinia virus which, at 230 nm, is larger than some bacteria. The virion consists of An outer shell, the capsid, made of protein. The capsid is responsible for protecting the contents of the core establishing what kind of cell the virion can attach to infecting that cell Some viruses contain other ingredients (e.g., lipids, carbohydrates), but these are derived from their host cells. an interior core containing the genome; either DNA or RNA The genes are few in number (3 - 100 depending on the species). They encode those proteins needed for viral reproduction that the host cell will not supply. Often, one or more proteins (enzymes) needed to start the process of reproduction within the host cell.

6. Human Influenza Highly contagious, spread by coughing and sneezing Most dangerous to the very young, very old, immunocompromised and pregnant Most are endemic influenza viruses, adapted to humans Influenza A (H3N2, some H1N1), influenza B viruses Drift: genetic changes little-by-little each year � reason to change vaccine strains Pandemics � shift: abrupt replacement of gene segment (reassortment of 8 gene segments) 1918: Spanish Flu (H1N1) - ?AIV genes 1957: Asian Flu (H2N2) - 3 AI & 5 human flu genes 1968: HK Flu (H3N2) - 2 AI & 6 human flu genes

7. Background: Disease Mechanism The influenza virus invades cells of the respiratory passages. Its hemagglutinin molecules bind to carbohydrate on the glycoproteins of the epithelial cells of the host. The virus is engulfed by receptor mediated endocytosis. The drop in pH in the endosome (endocytic vesicle) produces a change in the structure of the viral hemagglutinin enabling it to fuse the viral membrane with the vesicle membrane. This exposes the contents of the virus to the cytosol. The RNA enter the nucleus of the cell where fresh copies are made. These return to the cytosol where some serve as mRNA molecules to be translated into the proteins of fresh virus particles. Fresh virus buds off from the plasma membrane of the cell (aided by the neuraminidase) thus spreading the infection to new cells. The result is a viral pneumonia. It usually does not kill the patient (the 1918 pandemic was an exception; some victims died within hours) but does expose the lungs to infection by various bacterial invaders that can be lethal. Before the discovery of the flu virus, the bacterium Hemophilus influenzae was so often associated with the disease that it gave it its name. The influenza virus invades cells of the respiratory passages. Its hemagglutinin molecules bind to carbohydrate on the glycoproteins of the epithelial cells of the host. The virus is engulfed by receptor mediated endocytosis. The drop in pH in the endosome (endocytic vesicle) produces a change in the structure of the viral hemagglutinin enabling it to fuse the viral membrane with the vesicle membrane. This exposes the contents of the virus to the cytosol. The RNA enter the nucleus of the cell where fresh copies are made. These return to the cytosol where some serve as mRNA molecules to be translated into the proteins of fresh virus particles. Fresh virus buds off from the plasma membrane of the cell (aided by the neuraminidase) thus spreading the infection to new cells. The result is a viral pneumonia. It usually does not kill the patient (the 1918 pandemic was an exception; some victims died within hours) but does expose the lungs to infection by various bacterial invaders that can be lethal. Before the discovery of the flu virus, the bacterium Hemophilus influenzae was so often associated with the disease that it gave it its name.

8. What is a Pandemic? An global epidemic that occurs when a new virus �emerges� in the human population Occurs over a very wide area (several countries or continents) Usually affects a large proportion of the population--very limited or no immune response

9. What Makes an Influenza Pandemic? More cases than expected�widespread Sudden shift in strain Not expected (more pathogenic) No pre-existing immunity Duration Longer (up to 18 months) Multiple waves, each different May be some advance notice (not a lot) Medical infrastructure capacity compromised

10. Effects of Past Pandemics on the U.S.

11. The Seasonal or �Regular� Flu Centers for Disease Control and Prevention (CDC) Follows predicable patterns Caused by already circulating viruses Some immunity built up from previous exposures Usually healthy adults not at risk for serious complications �Normal� flu season about 226,000 Americans are hospitalized 36,000 die from the disease Most deaths occur among people older than 65 (90%) on average, 98 of every 100,000 seniors with the flu die. Prevention-competent vaccine & good hygiene practices Influenza costs the U.S. economy about $12 billion annually in direct medical costs and loss of productivity. As of March 18, 2006 103,188 cases �below average�

12. Pandemic virus production in 2 steps: AI virus infection of humans � limited infections Sustained human-to-human transmission � reassortment (hybrid virus)

13. Pandemic Strain Emergence: Direct Infection

14. Pandemic Strain Emergence: Reassortment of Influenza A Viruses

15. Pandemic Challenges Pandemics are different from other emergencies because it�s likely that almost all locations will be affected simultaneously Resources cannot be shifted geographically as in other emergencies Every country will be affected, but countries with better plans will be less vulnerable to terrorism and other threats during a pandemic

16. Latest Reported Avian Outbreaks

17. Cases in Humans

18. World Health OrganizationCumulative Deaths H5N1 as of 8 May 06

19. H5N1 Evolution in Humans Genetic changes in virus All human H5N1 isolates from Vietnam and Thailand resistant to adamantane family antiviral drugs Changing epidemiology in Vietnam (Clade 1) Increasing numbers of clusters Expanding age range Decreasing case fatality rate New mutation emerging in Indonesia (Clade 2) H5N1 is the most likely pandemic candidate TODAY

21. Intervention Strategies: Anti-Virals Moderate symptoms, shorten the recovery 1-2 days and make the infected less contagious Four anti-viral drugs are available for influenza A viruses: amantadine, rimantadine, oseltamivir, and zanamivir You can develop resistance In 2004, isolated H5N1 viruses from poultry and humans in Asia that were resistant to two of the medications (amantadine and rimantadine) in Asia Monitoring of avian viruses for resistance to influenza antiviral medications is ongoing

22. Intervention Strategies for Avian Flu: Vaccines There are currently no avian influenza vaccines approved in the U.S. for use on humans Vaccine candidate under development (Clade 1) Use as �pre-pandemic� vaccine 4-6 months to produce using current technology after the arrival of the organism

23. How Could H5N1 Get to USA?

24. Commercial Meat Imports

25. Captive birds Example: 2 eagles from Thailand through Germany to Belgium Possible but great distances reduce chances Illegal Commerce

26. Fighting cocks Entry mechanism from Thailand to Malaysia Possible risk vvNDV in Fresno CA in 2000, Asian Fighting Cocks Illegal Commerce

27. Raw or undercooked products DHS/PPQ � confiscation of products from Asia (pickled eggs, 1000 year eggs) Possible risk but would require feeding of scraps to birds Illegal Commerce

28. International Movement

29. Number of Episodes of Illness, Healthcare Utilization, and Death (HHS Plan, 2005)

30. When a Pandemic First Appears� There will not be enough vaccine There will not be enough antivirals The health care system will be stretched beyond its limits Many sectors of society will begin to be affected: schools, businesses, large public gatherings, �just-in-time� commerce, air travel, and so on�

31. Social Disruption May Be Widespread Strategies: Social Distancing= 3 feet between people Closing Places of Assembly�Suspend large social gatherings to limit spread �Snow Days� (weeks) and/or Furloughing �non-essential� workers�voluntary closings Restricted movement�border or geopolitical boundaries & quarantine protocols Plan for the possibility that usual services may be disrupted. These could include services provided by hospitals and other health care facilities, banks, stores, restaurants, government offices, and post offices. Prepare backup plans in case public gatherings, such as volunteer meetings and worship services, are canceled

32. Transportation Services May Be Disrupted Strategies: Screen all arriving passengers at ports of entry (n=348) Suspend Public Transportation to Limit Spread Think about how you can rely less on public transportation during a pandemic. For example, store food and other essential supplies so you can make fewer trips to the store. Prepare backup plans for taking care of loved ones who are far away. Consider other ways to get to work, or, if you can, work at home.

33. Schools May Be Closed for an Extended Period of Time Strategy: Close schools (snow-days) to limit spread Help schools plan for pandemic influenza. Talk to the school nurse or the health center. Talk to your teachers, administrators, and parent-teacher organizations. Plan home learning activities and exercises. Have materials, such as books, on hand. Also plan recreational activities that your children can do at home. Consider childcare needs.

34. Recap�Avian Influenza Why is Avian Flu dangerous May infect large populations of birds and poultry Has infected humans exposed to diseased birds May mutate to cause human infection At least 4 known subtypes determined in Asia Human to human transmission potential No natural human immunity No current approved vaccine Potential for a pandemic influenza High mortality rate (100% poultry / 80% human) Current antiviral drugs somewhat ineffective

35. US Government Strategy: Focus is on Saving Lives Slow spread, decrease illness and death, buy time Antiviral treatment and isolation for people with illness Quarantine for those exposed Social distancing Vaccine when available Local decisions

36. Criterion Required for a Pandemic The Avian H5N1 is widespread and endemic There are continuous outbreaks in poultry It has resulted in lethal mammalian infections Virus is evolving Sporadic human cases Mostly young and healthy Case fatality rate is 50% Rare instances of person-to-person transmission Sustained and rapid person-to-person transmission Throughout Asia, with spread to Russia and Europe, newly spreading to North AfricaThroughout Asia, with spread to Russia and Europe, newly spreading to North Africa

37. So�What YOU Can Do-Personally Wash your hands Every opportunity with soap and water Every opportunity with waterless hand cleaner Cover your mouth when you cough or sneeze Keep your environment clean Disinfect surfaces-using household disinfectants Common use items�door handles Personal use items�your phone Teach your kids�they will likely bring it home to you Stay home when you are sick

38. Foodborne Bird Flu Meat and eggs from birds associated with HPAI outbreaks should not be used for human food or animal feed, and everyone should follow recommended food handling practices to minimize risk of exposure. We don�t have good evidence that humans acquire bird flu by eating contaminated poultry meat or eggs. However, meat and eggs from birds infected with LPAI could be contaminated by virus in the bird�s droppings, and HPAI virus is present in meat and egg contents. Therefore, foodborne transmission is at least theoretically possible, and adequate precautions should be taken to prevent foodborne transmission. Tigers in Thailand zoos developed influenza after being fed dead chicken carcasses, and may represent foodborne transmission in that species. In addition, 2 people in Vietnam who drank raw blood from an infected duck became infected, but it isn�t clear what other exposures they had. While freezing and refrigeration help to preserve the virus, cooking and egg pasteurization conditions, except perhaps the process used for dried egg white powder, readily inactivate influenza virus.Meat and eggs from birds associated with HPAI outbreaks should not be used for human food or animal feed, and everyone should follow recommended food handling practices to minimize risk of exposure. We don�t have good evidence that humans acquire bird flu by eating contaminated poultry meat or eggs. However, meat and eggs from birds infected with LPAI could be contaminated by virus in the bird�s droppings, and HPAI virus is present in meat and egg contents. Therefore, foodborne transmission is at least theoretically possible, and adequate precautions should be taken to prevent foodborne transmission. Tigers in Thailand zoos developed influenza after being fed dead chicken carcasses, and may represent foodborne transmission in that species. In addition, 2 people in Vietnam who drank raw blood from an infected duck became infected, but it isn�t clear what other exposures they had. While freezing and refrigeration help to preserve the virus, cooking and egg pasteurization conditions, except perhaps the process used for dried egg white powder, readily inactivate influenza virus.

39. www.pandemicflu.gov

40. �Once again, nature has presented us with a daunting challenge: the possibility of an influenza pandemic�Together we will confront this emerging threat and together, as Americans, we will be prepared to protect our families, our communities, this great Nation, and our world� President George W. Bush November 2005

41. Questions ?????