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PANDEMIC INFLUENZA: FOCUS ON LOCAL PREPAREDNESS

PANDEMIC INFLUENZA: FOCUS ON LOCAL PREPAREDNESS. David J. Weber, MD, MPH Professor of Medicine, Pediatrics, and Epidemiology Associate Chief of Staff Medical Director, Hospital Epidemiology and Occupational Health University of North Carolina at Chapel Hill. Structure of the Influenza Virus.

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PANDEMIC INFLUENZA: FOCUS ON LOCAL PREPAREDNESS

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  1. PANDEMIC INFLUENZA:FOCUS ON LOCAL PREPAREDNESS David J. Weber, MD, MPH Professor of Medicine, Pediatrics, and Epidemiology Associate Chief of Staff Medical Director, Hospital Epidemiology and Occupational Health University of North Carolina at Chapel Hill

  2. Structure of the Influenza Virus Hemagglutinin (HA) 16 types in influenza A Neuraminidase (NA) 9 types in influenza A M2 Nucleoprotein (NP) ssRNA–highly mutable 8 segments-allows reassortment during double infection M1 Polymerase (P) Proteins Adapted from: Hayden FG et al. Clin Virol. 1997:911-42.

  3. INFLUENZA: BIOLOGY & IMPACT • Single-stranded, enveloped, RNA virus (orthomyxoviridae): Causes respiratory tract disease (pneumonia) • Sudden onset • More severe pneumonia during pregnancy • No carrier state but inapparent disease may occur • Influenza A • Potentially severe illness; epidemic and pandemics • Rapidly changing • Hemagluttinin (HA) 16 types; neuraminidase (NA) 9 types • Influenza B • Usually less severe illness; may cause epidemics • More uniform • Influenza C • Usually mild or asymptomatic illness

  4. ENVIRONMENTAL SURVIVALOF INFLUENZA A Efficacy of antiseptics Alcohol 60% gel, >99.99% reduction in 20 sec Ethanol 75%, >99.99% reduction in 20 sec Sattar SA, Tetro JA., 2006

  5. Influenza Disease Burden to U.S. Societyin an Average Year Deaths 25,000 - 72,000 Hospitalizations 114,000 - 257,500 Physician visits ~ 25 million Infections and illnesses 50 - 60 million Thompson WW et al. JAMA. 2003;289:179-86. Couch RB. Ann Intern Med. 2000;133:992-8. Patriarca PA. JAMA. 1999;282:75-7. ACIP. MMWR. 2004;53(RR06):1-40.

  6. SEASONAL INFLUENZA, PEAK MONTH,1976-2009

  7. Antigenic Drift

  8. Antigenic Shift

  9. Hampson AW, Mackenzie JS. MJA 2006;185:S39-43

  10. De Clercq E. Nature Rev 2006;5:1015-25

  11. INFLUENA PANDEMICS IN THE 20th CENTURY HHS Pandemic Influenza Plan, October 2005

  12. NY Times, 30 April 2009

  13. INFLUENZA AND PNUEMONIA MORTALITY, US, 1911-17 VS 1918

  14. PANDEMIC INFLUENZA PLANNING CHALLENGES • Pandemic strain unknown • The ability of the virus to rapidly spread worldwide • Simultaneous outbreaks throughout the US, limiting the ability of any jurisdiction to provide assistance to other areas • People may be asymptomatic while infectious • Long duration (>2 years) and multiple waves • Enormous demands on the healthcare system • Need for surge capacity: Medications, ventilators, beds, personnel • Personnel: Exhaustion, concerns about infection • Maintaining social distancing • Providing adequate antivirals including distribution/allocation • Vaccine development and distribution/allocation

  15. PANDEMIC INFLUENZA PLANNING ASSUMPTIONS • Most likely pandemic strain H5N1 (ongoing epidemic since 1999) • Pandemic likely to start in Asia and then spread to US • Mitigation strategies will limit epidemic: Social distancing, antivirals, vaccines • Pandemic will be characterized by distinctive waves • Susceptibility to the pandemic influenza virus will be universal • Highest infection rate among school-aged children (~40%) • Highest morbidity and mortality among the elderly • Asymptomatic persons may transmit infection • Antivirals likely in to be in short supply • Vaccine will be not be available for >6 months • Number of hospitalizations and deaths will depend on virulence

  16. Stochasic model - Germann TC, et al. PNAS 206;103:5935-5940

  17. MODELING AN INFLUENZA PANDEMIC:CONCLUSIONS • Social distancing (travel restrictions, closing schools) • Travel restrictions with >99% efficacy required to increase time between exports to the order of weeks • Delays epidemic and decreases peak • Limited effect on total number ill, hospitalized, or dead • Antivirals • Likely to decrease total number infected • Requires early therapy or long-term prophylaxis for efficacy • Adequate stockpile and distribution key • Vaccines • Must be available early in epidemic • Most effective if provided to children with leftover vaccine going to middle aged adults

  18. PANDEMIC INFLUENZA PLANNING ASSUMPTIONS • Most likely pandemic strain H5N1 (ongoing epidemic since 1999) (-) • Pandemic likely to start in Asia and then spread to US (-) • Mitigation strategies will limited epidemic: Social distancing, antivirals, vaccines (-) • Pandemic will be characterized by distinctive waves (-) • Susceptibility to the pandemic influenza virus will be universal • Highest infection rate among school-aged children (~40%) (-) • Highest morbidity and mortality among the elderly (-) • Asymptomatic persons may transmit infection (+) • Antivirals likely in to be in short supply (-) • Vaccine will be not be available for >6 months (+) • Pandemic influenza strain likely have increased virulence (-)

  19. WHO INFLUENZA PANDEMIC ALERT,11 JUNE 2009 (alert raised to phase 6)

  20. ESTIMATES OF NOVEL H1N1 IMPACT President’s Council of Advisors on Science and Technology, 7 Aug 2009

  21. NOVEL INFLUENZA H1N1, 2009CURRENT EPIDEMIOLOGY • Unique strain: Includes genetic components of human, avian, and swine origin • Worldwide outbreak • Efficient human-to-human transmission documented • Susceptible to antivirals (oseltamivir and zanamivir) but oseltamivir resistance described • Median age, US = 12 (highest infection incidence, 5-24 years) • Older individuals may have cross-reacting antibodies (i.e., partial protection) • Risk factors: • Obesity (BMI >30) and morbid obesity (BMI >40) a newly described risk for severe illness • Pregnant women: Death rate 4-6x higher than general public

  22. Gather D. J Clin Virol 2009;45:174-178

  23. Emergence of Quadruple-Reassortant H1N1/09 Garten et al., Science, 2009; 325:198

  24. IMPACT OF NOVEL H1N1 • Worldwide (WHO, 8 January) • 12,799 confirmed deaths; 208 countries/territories reported activity • US (CDC, April to 14 November) • 47 (range, 34-67) million cases • 213,000 (range, 154,000-303,000) hospitalizations • 9,820 (range, 7,070-13,930) deaths • North Carolina (NC Health Dept., 13 October) • 81 deaths {since April 2009} • UNC Hospitals (Hospital Epipidemiology, 4 January) • 115 hospitalizations, 5 deaths

  25. H1N1 EPIDEMIOLOGY, US • Hospitalization rate (US, 15 April to 24 July, 2009) • Cases: 43,771 • Hospitalizations: 5,011 (11.4%) • Deaths: 302 (0.69%) • Secondary attack rate • Acute respiratory illness: 18% to 19% • Definition: >2; fever, cough, sore throat, rhinorrhea • Influenza-like illness: 8% to 12% • Definition: Fever plus cough or sore throat • Generation time • Acute respiratory illness: 2.0-3.1 days • Influenza-like illness: 2.4-3.1 days

  26. International Epidemiology International Co-circulation of 2009 H1N1 and Seasonal Influenza (As of 4 January 2010)

  27. NOVEL H1N1,OUTBREAK CURVE, MEXICO,11 MARCH – 29 MAY

  28. H1N1, NEW ZEALAND EXPERIENCE MMWR 2009;58:918-21

  29. ILI REPORTED BY US OUTPATIENT ILINet

  30. INFLUENZA ACTIVITY, US, BY VIRAL TYPE

  31. H1N1 SURVEILLANCE, CDC,30 AUGUST TO 2 JANUARY

  32. H1N1 SURVEILLANCE, UNC

  33. Cough 98% Subject fever 96% Fatigue 89% Headache 82% Nausea 55% Stomach ache 50% Diarrhea 48% Shortness of breath 48% Joint pain 46% Max temperature 39.0 oC (102.2 oF) Temperature range 37.2-40.0 39.0 oC (99.0-104.0 oF) 95% reported subjective fever PLUS cough or sore throat NOVEL INFLUENZA H1N1, 2009:SYMPTOMS MMWR. NYC. 2009;58(dispatch;1-3

  34. H1N1 CASES RATE, US,BY AGE GROUP 15 April to 24 July, CDC

  35. Children Fast breathing or trouble breathing Bluish or gray skin color Not drinking enough fluids Severe or persistent vomiting Not waking up or not interacting Being so irritable that the child does not want to be held Flu-like symptoms that improve but then return with fever and worse cough Adults Difficulty breathing or shortness of breath Pain or pressure in the chest or abdomen Sudden dizziness Confusion Severe or persistent vomiting Flu-like symptoms that improve but then return with fever and worse cough WARNING SIGNS FOR WHEN A PERSON SHOULD SEEK MEDICAL CARE

  36. PERSONS AT HIGH RISK OF COMPLICATIONS FROM H1N1 INFLUENZA • Age < 2 years • Age >65 years • Pregnant women • Immunosuppression: HIV infection, chemotherapy • Persons with metabolic disorders: Diabetes, chronic renal failure, chronic liver failure, sickle cell anemia • Persons with cardiovascular disorders: Congestive heart failure (not hypertension) • Persons with compromised respiratory function: Cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders • Persons with respiratory disorders: Asthma

  37. CDC 2 Oct

  38. SYMPTOMS OFHOSPITALIZED PATIENTS

  39. H1N1 HOSPITALIZATION RATE(per 100,000), BY AGE GROUP

  40. AGE GROUPS OF HOSPITALIZED PATIENTS: SEASONAL VERSUS NOVEL INFLUENZA MMWR 2009;58(RR-10)

  41. MMWR 2009:58;749

  42. H1N1 IN HOSPITALIZED PATIENTS • High frequency of ARDS, pulmonary emboli, acute renal failure, and/or septic shock • Increased LDH and CPK • Infection characterized by severe hypoxemia and hypoxemic deaths • Frequent need for high-frequency oscillatory ventilation (HFOV) or extracorporeal membrane oxygenation (ECMO) • High frequency of secondary bacterial pneumonias • Consider empiric antibacterial therapy • Consider higher oseltamivir dosing (i.e., 150 mg PO 2x/d) and/or longer therapy (e.g., 10 days)

  43. H1N1 US DEATHS,BY AGE GROUPS, US

  44. H1N1 US ILLNESS AND DEATHS,BY AGE GROUPS, MEXICO Chowell G, et al. NEJM 2009;361:674-9

  45. MMWR 2009;58: 941-47

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