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Influenza

Influenza. Highly infectious viral illness First pandemic in 1580 At least 4 pandemics in 19th century Estimated 21 million deaths worldwide in pandemic of 1918-1919 Estimated that $4.6B spent annually on direct medical costs in US/yr 20-40K adult deaths per yr in US. Abbreviated MOA

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Influenza

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  1. Influenza • Highly infectious viral illness • First pandemic in 1580 • At least 4 pandemics in 19th century • Estimated 21 million deaths worldwide in pandemic of 1918-1919 • Estimated that $4.6B spent annually on direct medical costs in US/yr • 20-40K adult deaths per yr in US

  2. Abbreviated MOA • Virus grows best around 25 C, doesn’t grow well at 37 C • Virus binds to cell surface receptor via hemagglutinin (H) • virus-mediated fusion, via pH triggered change in conformation

  3. Abbreviated MOA cont Neuraminidase (N) acts late in life cycle and aids in release of viral particles from Infected surfaces H and N used to type viral strains and as antigens they provide protection against infection

  4. H is the major antigen, 5 major sites of variability leading to new strains

  5. Influenza Virus Strains Single-stranded RNA virus • Type A - moderate to severe illness - all age groups - humans and other animals • Type B - milder disease - primarily affects children - humans only • Type C - rarely reported in humans - no epidemics

  6. Type of nuclear material Neuraminidase Hemagglutinin A/Fujian/411/2002 (H3N2) Virus type Geographic origin Strain number Year of isolation Virus subtype Influenza Virus

  7. Influenza Antigenic Changes • Hemagglutinin and neuraminidase antigens change with time • Changes occur as a result of point mutations in the virus gene, or due to exchange of a gene segment with another subtype of influenza virus • Impact of antigenic changes depend on extent of change (more change usually means larger impact)

  8. Influenza Antigenic Changes • Antigenic Drift • minor change, same subtype • caused by point mutations in gene • may result in epidemic • Example of antigenic drift • in 2002-2003, A/Panama/2007/99 (H3N2) virus was dominant • A/Fujian/411/2002 (H3N2) appeared in late 2003 and caused widespread illness in 2003-2004

  9. Influenza Antigenic Changes • Antigenic Shift • major change, new subtype • caused by exchange of gene segments • may result in pandemic • Example of antigenic shift • H2N2 virus circulated in 1957-1967 • H3N2 virus appeared in 1968 and completely replaced H2N2 virus

  10. Impact of Pandemic Influenza • 200 million people could be affected • Up to 40 million require outpatient visits • Up to 700,000 hospitalized • 89,000 - 200,000 deaths

  11. Influenza Pathogenesis • Respiratory transmission of virus • Replication in respiratory epithelium with subsequent destruction of cells • Viremia rarely documented • Viral shedding in respiratory secretions for 5-10 days

  12. Influenza Clinical Features • Incubation period 2 days (range 1-4 days) • Severity of illness depends on prior experience with related variants • Abrupt onset of fever, myalgia, sore throat, nonproductive cough, headache

  13. Influenza Complications • Pneumonia • secondary bacterial • primary influenza viral • Reye syndrome • Myocarditis • Death 0.5-1 per 1,000 cases

  14. Impact of Influenza • ~36,000 excess deaths per year • >90% of deaths among persons >65 years of age • Average of >200,000 influenza-related excess hospitalizations • 57% of hospitalizations among persons <65 years of age

  15. Influenza Epidemiology • Reservoir Human, animals (type A only) • Transmission Respiratory Probably airborne • Temporal pattern Peak December – March in temperate climate May occur earlier or later • Communicability 1 day before to 5 days after onset (adults)

  16. Month of Peak Influenza Activity United States, 1976-2006 43% 20% 13% 13% 3% 3% MMWR 2006;55(RR-10):22

  17. Influenza Vaccines • Inactivated subunit (TIV) • intramuscular • Trivalent • ≥ 6 months • Live attenuated vaccine (LAIV) • intranasal • Trivalent • 5-49 yrs

  18. Composition of the 2005-2006 Influenza Vaccine* • A/California/7/2004 (H3N2) (A/New York/55/2004) • A/New Caledonia/20/99 (H1N1) • B/Shanghai/361/2002 (B/Jilin/20/2003 or B/Jiangsu/10/2003) *strains in (parenthesis) are antigenically identical to the selected strains and may be used in the vaccines

  19. Transmission of LAIV Virus • LAIV replicates in the nasopharyngeal mucosa • Mean shedding of virus 7.6 days – longer in children • One instance of transmission of vaccine virus documented in a child care setting • Transmitted virus retained attenuated, cold-adapted, temperature-sensitive characteristics • No transmission of LAIV reported in the U.S.

  20. Inactivated Influenza Vaccine Efficacy • 70%-90% effective among healthy persons <65 years of age • 30%-40% effective among frail elderly persons • 50%-60% effective in preventing hospitalization • 80% effective in preventing death

  21. LAIV Efficacy in Healthy Children • 87% effective against culture-confirmed influenza in children 5-7 years old • 27% reduction in febrile otitis media (OM) • 28% reduction in OM with accompanying antibiotic use • Decreased fever and OM in vaccine recipients who developed influenza

  22. LAIV Phase 3, 10 sites, 1602 kids, 1-6 yrs old 1 dose  89% efficacy 2 doses  94% efficacy 1 year later 100% effective against 3 strains administered previously, plus 98% effective against the new circulating strain A/Sydney PLUS 98% effective both years against ear infections

  23. LAIV Phase 3, 92 adults, 18-45 years 1 dose LAIV  85% efficacy 1 dose TIV  71% efficacy 1 year later, A/Sydney LAIV  100% efficacy TIV  0% efficacy

  24. Timing of Inactivated Influenza Vaccine Programs • Actively target vaccine available in September and October to persons at increase risk of influenza complications, children <9 years, and healthcare workers • Vaccination of all other groups should begin in November • Continue vaccinating through December and later, as long as vaccine is available

  25. Influenza Vaccine Recommendations • Healthcare providers, including home care* • Employees of long-term care facilities • Household contacts of high-risk persons *LAIV should not be administered to healthcare workers who have contact with severely immunosuppressed persons who require hospitalization and care in a protective environment

  26. Influenza Vaccination of Healthcare Personnel Only 42 percent of U.S. healthcare personnel were vaccinated in 2004 • Reduction in nosocomial influenza and influenza-related deaths • Reduction in staff illness and illness-related absenteeism • Reduction of direct medical costs and indirect costs from work absenteeism

  27. Reasons HCP Do Not Receive Influenza Vaccine • Concern about vaccine adverse events • Perception of a low personal risk of • influenza virus infection • Insufficient time or inconvenience • Reliance on homeopathic medications • Avoidance of all medications • Fear of needles MMWR 2006;55 (RR-2)

  28. Inactivated Influenza Vaccine Adverse Reactions Local reactions 15%-20% Fever, malaise not common Allergic reactions rare Neurological very rare reactions

  29. Adverse Reactions in men

  30. Live Attenuated Influenza VaccineContraindications and Precautions • Children <5 years of age* • Persons >50 years of age* • Persons with chronic medical conditions* • Children and adolescents receiving long-term aspirin therapy* *These persons should receive inactivated influenza vaccine

  31. Live Attenuated Influenza VaccineContraindications and Precautions • Immunosuppression from any cause • Pregnant women* • Severe (anaphylactic) allergy to egg or other vaccine components • History of Guillian-Barré syndrome • Moderate or severe acute illness *These persons should receive inactivated influenza vaccine

  32. LAIV Storage and Handling • Must be stored at < 5°F (-15°C )* • May be stored in a frost-free freezer with a separate door • May be thawed in a refrigerator and stored at 35°-46°F (2°-8°C) for up to 60 hours before use • Should not be refrozen after thawing *a refrigerator-stable formulation of LAIV may be available beginning in the 2007-2008 influenza season

  33. Influenza Antiviral Use, 2006-2007* • Neither amantadine nor rimantadine be used for the treatment or chemoprophylaxis of influenza A infections in the United States during the 2006- 2007 influenza season • Oseltamivir (Tamiflu) or zanamivir (Relenza) should be prescribed if an antiviral drug is indicated for the treatment or chemoprophylaxis of influenza *see influenza ACIP statement or CDC influenza website for details

  34. Influenza Surveillance • Monitor prevalence of circulating strains and detect new strains • Estimate influenza-related morbidity, mortality and economic loss • Rapidly detect outbreaks • Assist disease control through rapid preventive action

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