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Respiratory Viruses

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  1. Respiratory Viruses Influenza A, B,Parainfluenza 1, 2, 3Respiratory Syncytial VirusHuman Metapneumovirus AdenovirusRhinovirusCoronavirusCytomegalovirus

  2. Respiratory VirusesCanada, 2007-2008 *68% H1N1; 32% H3N2

  3. Respiratory Outbreaks in Ontario Institutions, 2005-06

  4. Influenza in Canada • approx. 5 million (1 in 6) infected/yr • 50-70,000 hospital admissions/yr • 4,000-6,000 death each year (6th leading cause of death) • 1.5 million work-days lost each year • >90% of serious morbidity/mortality in the elderly

  5. Population-Based Surveillance Laboratory-Confirmed InfluenzaInpatients, Toronto 2005 Rate per 100,000/yr Incidence Mortality McGeer, TIBDN, Clin Infect Dis 2007

  6. Influenza Virus • family Orthomyxoviridae • enveloped RNA virus, 80-120 nm • types A and B distinguishedby antigenic differences in nucleoprotein and matrix protein

  7. Influenza Virus

  8. Influenza Virus Life Cycle

  9. InfluenzaTransmission • respiratory droplets • contact (direct, fomites) • ? airborne

  10. Hand hygiene to prevent influenza transmission in households Cowling, Ann Int Med 2009

  11. Loeb, JAMA 2009

  12. Viral shedding Illness Exposure Influenza Day 0 1 2 3 4 5 6 7 8 9 10

  13. Clinical Characteristics of Influenza 40 103 39 102 O C Onset of Illness 101 Oral Temperature (o F) 38 100 99 37 98 0 1 2 3 4 5 6 7 8 Days after onset Nasal congestion Sore throat Muscle pains Headache Cough Malaise Infectivity / Virus isolation

  14. InfluenzaComplications • pneumonia (viral, bacterial) • sinusitis, otitis media, bronchitis • myocarditis, encephalitis,Reye’s syndrome

  15. Influenza

  16. InfluenzaDiagnostic Specimens • NP swab/aspirate/washing • throat swab/washing • best yield if obtained within3 days of symptom onset

  17. InfluenzaDiagnosis • antigen detection (DFA, EIA) • viral isolation • serology • RT-PCR

  18. INFLUENZAAnti-Virals • Amantadine/Rimantadine • Neuraminidase inhibitors oseltamivir zanamivir

  19. Amantadine/Rimantadine • M2 protein inhibitors • modest efficacy against influenza A; no activity against influenza B • toxicity • viral resistance(point mutations in M2 protein)

  20. Neuraminidase Inhibitors • Zanamivir (Relenza)orally inhaled • Oseltamivir (Tamiflu)oral

  21. Neuraminidase • promotes release of virus from infected cells • prevents formation of viral aggregates • prevents viral inactivationby respiratory mucus

  22. Neuraminidase Inhibitors • active against influenza A and B • efficacy documented fortreatment and prophylaxis • safe, well tolerated

  23. Neuraminidase InhibitorsTreatment Studies • approx. 30% reduction induration of symptoms (1-2 days) • approx. 40% reduction inseverity of symptom scores • reduced complications • reduced duration of viral shedding

  24. Oral oseltamivir for influenza (adults)Effect on antibiotic use and hospitalizations Placebo Oseltamivir LRT complicationsleading to use of antibiotics All hospitalizations 50% 55% 52% 59% Patients (%) 62% * * 61% ** *p<0.001 vs placebo **p<0.05 vs placebo Kaiser Arch Intern Med 2003

  25. Survival in adult patients with laboratory-confirmed influenza requiring hospital admission, TIBDN surveillance, 2004-2008 McGeer, CID 2007 McGeer, CID 2007

  26. Neuraminidase InhibitorsProphylaxis • Post exposure prophylaxis family/household contacts nursing home outbreaks • Seasonal prophylaxis

  27. Neuraminidase Inhibitors

  28. Anti-Viral Drug ResistanceUSA, 2008-2009 • Seasonal H1N1 - >99% oseltamivir resistant • Seasonal H3N2 - 100% amantadine resistant • Pandemic H1N1 - 0.5% oseltamivir resistant - 100% amantadine resistant CDC, Oct. 2009

  29. Influenza Vaccine • inactivated whole – virus vaccine • intact purified virus particles • split – virus vaccine • lipid membrane disrupted • purified surface – antigen vaccine

  30. Influenza Vaccine (2009-10) A/Brisbane/10/2007 (H3N2) A/Brisbane/59/2007 (H1N1) B/Brisbane/60/2008

  31. InfluenzaVaccine Efficacy • young >80% effective • elderly >70% effective, 80% effective in preventing death

  32. Effectiveness of Influenza Vaccine in Community-Dwelling Elderly over 18 Seasons Nichol, NEJM 2007

  33. Influenza VaccineAdverse Effects • local arm pain, erythema (30%) • fever, malaise, myalgias (5-10%) • Guillain-Barré Syndrome - 1976

  34. Influenza Vaccination in Healthy Adults Nichol, NEJM 1995

  35. Contraindication toInfluenza Vaccine • hypersensitivity to eggs • delay vaccine if acute febrile illness

  36. Live, AttenuatedInfluenza Vaccine • FluMist™ (MedImmune Inc.) • live, attenuated virus (trivalent);temperature-sensitive (limited replication at 38°C) • intra-nasal spray

  37. Monto, N Engl J Med 2009

  38. Universal Influenza VaccinationOntario, 2000-2008 As compared to other provinces, Ontario experienced • greater decrease in influenza-related mortality (RR 0.26 vs. 0.43) • greater decrease in influenza-related hospitalizations (RR 0.25 vs. 0.44) Kwong, PLoS Med 2008

  39. Impact of Universal Influenza Vaccination Dose-response relationship between influenza vaccination rate and change in respiratory antibiotic prescriptions before/after 2000.Kwong, Clin Infect Dis2009

  40. Influenza Pandemics