Influenza Informed and Prepared

1. Influenza Informed and Prepared Louise S. Gresham PhD, MPH NAAEP April 12, 2007

2. Our Discussion • The Influenza Viruses • Possibility of Influenza Pandemic • Pandemic Preparedness & Response • Point of Dispensing (POD) • Continuous Operations Planning (COOP)

3. Part One: The Influenza Viruses www.cdc.gov

4. Anatomy of the Influenza A Virus • Orthomyxoviridae • RNA • Surface glycoproteins: • Hemagglutinin (H) initiates penetration into host cell (16 types) • Neuraminidase (N) allows new virions to escape host cell (9 types)

7. Part Two: Possibility of Influenza Pandemic www.cdc.gov

8. Influenza Pandemics in the 20th Century

9. Why Scientists Feel a Pandemic is Imminent (cont’d) • H5N1 has caused unprecedented large wild bird die offs since2002, e.g. 6000 birds at Qinghai Lake, China in April, 2005 • Overlapping migratory flyways suggest that North American wild birds will probably eventually become infected

10. Why Scientists Feel a Pandemic is Imminent (continued) • … not previously known to have symptomatic infections from influenza. The recent deaths of housecats and tigers from H5N1 demonstrate the ability of the virus to extend its host range • Mammal-to-mammal transmission has been observed in tigers, ferrets, and housecats, another first

11. Why Scientists Feel a Pandemic is Imminent (continued) In seasonal influenza, it is the very old and very young that are most at risk of severe disease and death. In pandemics, young to middle aged adults are at increased risk. This pattern is being seen with H5N1

12. Robert Webster, PhD: the Father of Influenza Virology “[H5N1] is the worst flu virus I have ever seen or worked with or read about. We have to prepare as if we were going to war—and the public needs to understand that clearly. If it does happen, and I fully expect that it will, there will be no place for any of us to hide…The virus is a very efficient killer.”

13. Human Influenza A/(H5N1) • *Total cases since 2003 285 (170 deaths) • Vietnam 93 (42) none in 2007 • Indonesia 81 (63) • Thailand 25 (17) none in 2007 • Egypt 29 (13) • China 24 (15) * As of 3/29/07

14. Why do we have to keep our guard up? • Once it becomes transmissible person-to-person, wild bird and poultry disease becomes irrelevant • Two ways it can go person-to-person: • Sequential adaptive mutations • Reassortment event

15. Human H5N1 Disease • Incubation period may be longer than regular flu’s 48 hours (up to 8 days) • Persons may be contagious a day before they have symptoms • Initially looks like regular influenza • Perhaps fewer upper respiratory symptoms • Perhaps greater vomiting and diarrhea • May rapidly progress to a viral pneumonia • In severe cases: • Respiratory failure • Secondary multiple organ failure • May have associated neurologic symptoms

16. Human H5N1 Current Case Definition(subject to change) ALL FOUR components must be present: • Correct symptom complex • Correct exposure • Correct travel • Correct timing of travel

17. Case Definition, continued • Symptom complex: • Either, radiographically confirmed pneumonia, acute respiratory distress syndrome (ARDS), or other severe respiratory illness for which an alternate diagnosis has not been established • Testing for avian influenza A (H5N1) is indicated • Or, Fever >100.4° F (38 ° C) AND one or more of the following: cough, sore throat, shortness of breath • Testing for avian influenza A (H5N1) should be considered on a case-by-case basis in consultation with local health departments

18. Case Definition, continued 2. Exposure (Risk behaviors): • Direct contact with domestic poultry* (e.g. touching sick or dead chickens or ducks or well-appearing ducks) • Consumption of uncooked poultry* or poultry* products • Direct contact with surfaces contaminated with poultry* feces • Close contact (within 1 meter) with a known of suspected human case of H5N1 *Poultry is defined as domestic chicken, turkeys, ducks or geese raised for meat or eggs

19. Case Definition, continued 3. Travel history:use the OIE list of countries with H5N1 in poultry, not wild birds For current information on H5N1 cases in animals (click on graph at the top of the page): http://www.oie.int/downld/AVIAN%20INFLUENZA/A_AI-Asia.htm 4. Timing of travel: must be within TEN DAYS of onset of symptoms

20. What Specimens are Needed for Diagnosis? • Upper AND LOWER respiratory specimens for RT-PCR testing are optimal • H5N1 preferentially attaches to receptors in the lower respiratory tract • Lower respiratory specimens include: • Sputum • Suctioned secretions from ETT • Bronchoalveolar lavage fluid • Pleural tap fluid • Specimens obtained on MULTIPLE DAYS are optimal to rule out the diagnosis • Rapid flu tests neither rule in nor rule out the disease

21. BREAK

22. The Three Prerequisites for an Influenza Pandemic • The virus must be a novel one, to which there is universal immunologic naiveté. Achieved by H5N1 • The virus must be highly pathogenic to man. Achieved by H5N1 • The virus must transmit between humans in an efficient and sustained manner. Not yet achieved by H5N1

23. Has Human-to-Human Transmission Occurred Yet? • Probably yes, but very rare and not sustained (no second generation transmission) • Thailand, early 2005: a mother without other risk factors contracted the illness after providing close physical care to her ill child • Conflicting study results on whether healthcare workers have increased evidence of antibody production to the disease after caring for patients with H5N1 • A few other small family clusters look suspicious, but not conclusive • No human-to-human transmission detected in the recent cases in Turkey, Indonesia, Iraq, Azerbaijan, or Egypt

24. Latest Risk Factor Analysis • Case-control study of all lab-confirmed AI cases in Vietnam, 2004 (N = 28) • Preparing ill or dead poultry for consumption: OR = 8.99 (95% CI 0.98 – 81.99) • Sick or dead poultry in household <= 7 days prior to illness: OR = 4.94 (95% CI 1.21 – 20.20) • Lack of indoor water source: OR = 6.46 (95% CI 1.20 – 34.81) • NOT significant: • Raising healthy-appearing poultry • Preparing healthy-appearing poultry for consumption • Exposure to persons with acute respiratory illness Dinh, P. et al. Volume 12 No. 12 December, 2006

25. Food Safety • No epidemiologic link between eating cooked poultry products and human disease • To date, high pathogenicityH5N1 (HPAI H5N1) has not been found in North America in wild birds or poultry • Cooking temperatures of 165° F or greater are sufficient to kill influenza viruses • Poultry should not be pink or bloody; eggs should not have runny yolks • The same kitchen safety practices as for bacterial pathogens, such as campylobacter or salmonella

26. Part Three: Pandemic Preparedness & Response www.cdc.gov

27. CDC Modeling Studies on Impact of Pandemic

28. World Health Organization (WHO) Pandemic Phases Interpandemic Phase • Phase 1: No evidence of novel viruses in animals • Phase 2: Novel virus in animals, no human cases Pandemic Alert • Phase 3: No or very limited human-to-human transmission (current phase) • Phase 4: Evidence of increased human-to-human transmission • Phase 5: Evidence of significant human-to-human transmission Pandemic • Phase 6: Efficient and sustained human-to-human transmission

30. Infection Control for HCW’s Two types of transmission for respiratory pathogens • Droplet transmission • Particles over 5 μ in diameter • Particles fall to the floor within 3 ft of patient • Surgical masks sufficient • Examples: seasonal influenza, pneumococcal pneumonia Airborne transmission (aka “droplet nuclei”) • Particle size under 5 μ in diameter • Remain suspended over large distances and long times • N95 masks recommended • Examples: smallpox, measles, TB ? ? What will the transmission characteristics of avian influenza be?

31. What’s NEW in Infection Control • Guidance created for pandemic influenza; even though not meant to apply to avian influenza, it will likely be applied • New distinction made between long-range and short-range aerosol transmission • “It would be prudent” for N95 respirators to be used for the routine care of suspect or confirmed PI patients • They should definitely be used for aerosol-generating procedures • Negative pressure rooms do not have to be used whenever N95’s are recommended, but should be used for aerosol-generating procedures

32. Aerosol-Generating Procedures • Examples: • Induced sputum collection • Nebulizer treatments for asthma • Intubation • Suctioning through ETT • Bronchoscopy • N95 respirators and eye protection for all personnel in the room • Negative pressure rooms should be used Influenza patient in Hong Kong

33. High Efficiency Particle Arresting (HEPA) Filters • HEPA filters remove a minimum of 99.97% of contaminants ≥ 0.3 microns (a micron is 1/1000 of a millimeter) • A good alternative when air must be recirculated • Workers should be instructed not to stand between patient and HEPA filter • Protocol for cleaning/replacing filters safely should be in place

34. What Products Kill Influenza on Environmental Surfaces? http://www.epa.gov/opp00001/factsheets/avian_flu_products.htm • Lipid bilayer membranous covering • Susceptible to heat and many detergents and disinfectants

35. Health Care Surge Capacity • HRSA Grants: originally developed for bioterrorism threat, the goal is to develop ability to care for increased numbers of critically ill • 500 persons/million population or 1500 persons in SD county • Includes surge capacity tents with negative pressure rooms, extra ventilators, and other equipment • Strategic National Stockpile (SNS) • Requires a declaration of emergency by the governor • Mechanism of rapid deployment of supplies and medications (12 hour push-packs) • Points of distribution (PODs) will used

36. Public Health Measures • Isolation: Physical separation of ill persons from well persons • Recommended isolation period is 14 days; may be longer for children and the immunocompromised • Quarantine: Physical separation of well persons that have been exposed to an infectious illness from the non-exposed • Recommended quarantine period is 10 days • The optimal location is the person’s own home • Modern emphasis on balancing the rights of individuals with the need to protect the community • Important measures early in the pandemic to limit the spread of disease

37. WHO Phase-based PH Responses Phase 3 Isolation No quarantine Phase 4 The “slippery slope” Isolation Quarantine Phase 5 Phase 6 Individual measures Community measures “Snow days” School closuresRestriction of nonessential gatherings Isolation No quarantine

38. Resources for Personal and Business Preparedness www.pandemicflu.gov has sections on: • Individual planning • Business planning • School planning • Health care planning • Faith-based organization planning • Community planning • Residential facility planning

39. Resources for Personal and Business Preparedness • www.cdc.gov/flu/avian/index.htmhas sections for: • Travelers • Poultry workers • US citizens living abroad • Airline industry workers • Persons who think they may have been exposed

40. Neuraminidase inhibitors Tamiflu (oseltamivir) and Relenza (zanamivir) Effectiveness (humans) Seasonal flu (prophylaxis): Both drugs: 70 – 80% effective in nursing homes and households Seasonal flu (treatment): Fewer hospitalizations (RCT) Less post-flu antibiotic use (RCT) Fewer deaths in nursing home cohorts (nonrandomized series) Viral shedding and symptom duration significantly shortened (RCT) New multicenter RCT showed 71% mortality reduction in hospitalized patients (A. McGeer) H5N1: insufficient data Good results in animals experimentally exposed to H5N1 Early institution Higher mg/kg doses Antiviral Drugs

41. Antiviral Drugs (cont’d) Neuraminidase inhibitors (cont’d) • Supply: 400 million courses/year projected for Tamiflu • Resistance • Seasonal flu: still rare, except in Japanese pediatric population • H5N1: occasional case studies of resistance developing in vivo Adamantanes (amantadine and rimantidine) • No longer recommended against seasonal flu (H3N2 91% resistant) • May be effective against H5N1 Clade 2 • Could have a valuable synergistic effect with NI’s

42. The Role of Seasonal Flu Vaccine Although the seasonal flu vaccine will not protect against the pandemic strain, lowering the prevalence of seasonal flu is an important measure to prepare the population for the pandemic: • Makes an epidemiologic investigation of pandemic flu more feasible • Reduces stress on an overburdened healthcare system • Reduces the risk of reassortment events 

43. A Pneumovax Shot is Recommended for Some People • Pneumovax prevents the most common type of bacterialpneumonia, caused by Streptococcus pneumoniae • Secondary bacterial pneumonia was a common complication in previous pandemics • Persons that qualify for a Pneumovax shot include: • All persons over 65 and under 2 years of age • Persons of any age with: • Chronic heart or lung disorders (excluding asthma) • Diabetes • Chronic liver or kidney disease • Immunosuppressive diseases

44. Avian Influenza (H5N1) Vaccine • Challengesto vaccine implementation: • Must wait until human-to-human transmission develops to formulate vaccine against that specific strain • Cannot use traditional technique of growing virus in embryonated chicken eggs, because H5N1 kills chicken eggs • It will take about six months to manufacture • Requires high level biosecurity facilities • Limited manufacturing surge capacity • Two shots a month apart will be necessary to develop immunity

45. Pandemic Response Strategy • In the first 6 – 9 months, “buying time” until pandemic vaccine is manufactured and distributed: • Social distancing measures • Quarantine and isolation • Judicious, risk-stratified use of antivirals • Treatment • Prophylaxis (unlikely with available quantities) • After 6 – 9 months: • Availability of pandemic vaccine • Rapid administration using Point of Distribution sites (POD’s) • Priority groups get vaccine first

46. Limited Manufacturing Surge Capacity • Bill introduced in the US Senate October, 2005, the "Biodefense and Pandemic Vaccine and Drug Development Act of 2005" • Would shortcut the testing procedures for new vaccines and drugs in case of a pandemic • Would protect vaccine makers from legal liability in case the drug causes adverse reactions. • Stiff opposition from consumer protection groups

47. What Antigen(s) Should Be Targeted? Clade 1: Thailand, Vietnam 2003-2005 Clade 2, subclade 1: Indonesia, 2005-2006 Clade 2, subclade 2: Middle East, Europe, Africa, 2005-2006 Clade 2, subclade 3: China, 2005-2006 Recommended by WHO for vaccine development

48. National Vaccination Priority Recommendations* *Approved by NVAC/ACIP committee on July 19, 2005

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50. 1. Personal and family planning 2. Business continuity planning What the Public Can Do to Prepare for the Pandemic