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Influenza Marc A Bellazzini, MD University of Wisconsin. Objectives Summarize history of influenza Describe influenza viral structure, antigenic composition and virus types Differentiate antigenic shift from drift

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Influenza Marc A Bellazzini, MD University of Wisconsin


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    1. Influenza Marc A Bellazzini, MD University of Wisconsin

    2. Objectives • Summarize history of influenza • Describe influenza viral structure, antigenic composition and virus types • Differentiate antigenic shift from drift • Describe clinical presentation, course and complications of influenza • Discuss laboratory assays for influenza • Describe anti-viral therapy for influenza • Summarize vaccination options for influenza

    3. Case A 9 year old girl returns from school with high fever, chills, muscle aches and cough. Several other school children are sick. Her illness progresses over 24 hours and her fever remains high. Her parents are now showing similar signs and symptoms.

    4. Case On the second day she develops increasing respiratory distress and dies at home. She is buried on Feb 24th, 1918.

    5. Flu Timeline Yearly Influenza United States More than 200,00 hospitalized 36,000 deaths 5-20% of population get flu Serious illness or death highest in those >65 and less than 2 years Asian flu pandemic H2N2 70,000 deaths United States 1957-58 2000 - beyond 1918-1919 1968-1969 World wide Severe illness 3-5 million cases 250,000-500,000 deaths WHO information 2008 Spanish flu pandemic H1H1 20-40% of population ill 20-40 million deaths worldwide 500,000 deaths United States Attack rate highest in young and middle aged Hong Kong Flu pandemic H3N2 34,000 deaths in United States

    6. Structure and Epidemiology of Influenza Virus

    7. Influenza Virus • Hemagglutinin (H) antigen • Antibodies to H antigen major determinant of immunity • Virus binds to cell receptor via H glycoprotein • Sixteen different subtypes H1, H2, H3 ... • Neuraminidase (N) antigen • Antibodies to N glycoprotein limit viral spread • Nine antigenic subtypes N1, N2, N3 ....

    8. Epidemics and Pandemics • Antigenic Shift • Pandemic (10-15 year cycle)‏ • Major antigenic variation • No immunity in population • Change in H and or N • H1N1 to H2N2 1957 pandemic • Re-assortment of genes between animal and human viruses • Antigenic Drift • Minor antigenic variation • Point mutation

    9. Influenza Virus Nomenclature A/Fujian/411/2002 (H3N2)‏ Virus Type Year Isolated Geographic Origin Strain Number Virus Subtype Wikipedia Accessed 09/02/08

    10. Influenza • Influenza A • Most common form of influenza • Found in ducks, chickens, pigs, whales, seals, horses • Influenza B • No H or N typing • Found in humans only • Influenza C • Typically minor respiratory illness

    11. CDC 2008

    12. University of Wisconsin Syndromic Surveillance 2007-2008 MARISSA UW Emergency Medicine Surveillance

    13. Influenza Clinical Considerations

    14. Transmission • Large particle respiratory droplets – cough & sneezing main method of transmission • Contact transmission with respiratory droplet contaminated surfaces possible • Airborne suspended small particle (< 5 um) transmission thought to be possible • - CDC

    15. Clinical • Abrupt onset of illness • Fever • Sore throat • Cough • Myalgia • Malaise • Rhinitis • Headache • Chills

    16. Clinical Differences in Children • Gastrointestinal – Vomiting and diarrhea • Fever and cough less likely to be reported • High mortality in children under 2 years of age • School aged children have highest attack rates of influenza • Children major source of transmission of influenza

    17. NEJM Dec 2005

    18. Influenza and bacterial co-infection in children • Influenza and bacterial co-infection S. aureus increasing • 2006-2007 • 73 influenza deaths children • 30/69 (44%) cases bacterial co-infection • 73% of those co-infected had S. aureus • 15 children had co-infection with MRSA • Pneumonia or Bacteremia associated with S. aeurus 5 fold increase compared to previous years. • www.cdc.gov accessed 01/03/08

    19. Clinical Course • Respiratory transmission – cough and sneezing • Abrupt onset of malaise, chills, fever, headache • Incubation 1-4 days • Young children may be infectious several days prior to symptom onset • Adults may be infectious one day prior to symptoms • Illness will usually resolve in 5 days • Viral shedding decreases 4-5 days after onset • Children may be infectious for more than 10 days • Cough and malaise may persist for two weeks

    20. Clinical Course • Exposure __ • Incubation __________ • Illness duration ________________ • Viral shedding adult ________________________ • Viral shedding child __________________________________________ • Cough and malaise __________________________________________________ • Day 1 Day 3 Day 5 Day 7 Day 9 Day 11 Day 13 Day 15 Day 17

    21. Complications of Influenza • Primary influenza pneumonia • Secondary bacterial pneumonia • Uncommon • Myocarditis • Pericarditis • Encephalitis • Transverse myelitis • Reyes syndrome in those taking ASA

    22. CDC 2008

    23. UW Laboratory Testing • NP W/A Nasopharyngeal Wash Aspirate • NS Nasal swab use flocked swab with UTM transport media • Culture performed in house. Must notify lab if concern for H5N1 then culture will be sent to state • FluMist may result in false positive EIA, DFA, PCR if administered within 21 days. • DFA only performed during respiratory virus season

    24. Vaccination

    25. Annual Influenza vaccination most effective method of preventing influenza virus infection and its complications. - CDC

    26. Vaccination has been shown to reduce hospitalizations and deaths in adults <65 years of • age with risk factors for influenza complications. • - CDC

    27. Impact of Vaccination • Vaccination of nursing home health care providers has significantly reduced mortality in nursing home patients. • Reductions in respiratory tract infections observed in household contacts of children who received influenza vaccination. • Studies also suggest reduction in respiratory illness in a community where school aged children were targeted for vaccination. • - CDC

    28. Vaccine preparation • Current vaccine composition based on last years surveillance data • Vaccine strains must be selected by Feb of each year • Takes 6-8 months for vaccine preparation • - CDC

    29. Trivalent inactivated influenza vaccine (TIV) can be used for any person aged >6 months. • Live, attenuated influenza vaccine (LAIV) may be used for healthy, nonpregnant persons aged 2-49 years. - CDC

    30. Vaccination Composition • 2007-2008 • A/Solomon Islands/3/2006 (H1N1) like - changed • A/Wisconsin/67/2005 (H3N2) like • B/Malaysia/2506/2004 like • 2008-2009 • A/Brisbane/59/2007 (H1N1) like - changed • A/Brisbane/10/2007 (H3N2) like - changed • B/Florida/4/2006 like - changed WHO Global Influenza Surveillance Network recommends Vaccine Composition

    31. Vaccination Timing • Should ideally be administered October-November • May be started in September • Can be administered later in season • Takes two weeks for immunity to build • Need yearly vaccination due to waning immunity and drift

    32. Inactivated Influenza Vaccine Dose • Intramuscular administration • 3 years of age to adult dose 0.5 ml • 6 months up to 35 months dose 0.25 ml • Children 6 months through 8 years of age should receive two doses of vaccine separated by 4 weeks if first time vaccination. • Contraindicated in those with significant egg allergy or allergy to influenza vaccine.

    33. Inactivated Influenza Vaccine • Efficacy • 70-90% effective in reducing laboratory confirmed influenza in healthy adults less than 65 years old • less effective in elderly • may be less effective in those with chronic medical conditions and immune compromised. • Side Effects • soreness at vaccination site • fever, malaise, myalgia may occur

    34. Inactivated Influenza Vaccine and GBS • 1976 swine influenza vaccine 1 additional case of GBS per 100,000 vaccinated • Annual incidence of GBS 10-20 per 1 million adults • Conflicting studies since 1976 however no definitive link between Influenza vaccination and GBS • In studies which showed increased incidence of GBS the increased risk would be 1 additional case of per 1 million vaccinated • Benefits far outweigh risks CDC 2008

    35. Live Attenuated Influenza Vaccine • Indicated in healthy non-pregnant persons 2-49 years old • Intranasal administration • 0.2 ml half dose sprayed in each nostril • Children 2-8 years of age should receive two doses separated by 4 weeks if previously un-immunized

    36. Live Attenuated Influenza Vaccine (LAIV)‏ • 85-92% effective • Not indicated for individuals with chronic serious medical conditions or immune compromise. • Should not be used in children less than 5 with wheezing • Should not be given to children who take ASA • Should not be given to those with egg allergy

    37. Live Attenuated Influenza Vaccine (LAIV)‏ • Those who come in contact with immune compromised individuals should not be vaccinated with LAIV • Those who receive LAIV may shed live virus at low levels • Shedding diminishes after 3 days from vaccination • Rarely transmitted to un-vaccinated persons CDC 2008

    38. Live Attenuated Influenza Vaccine Side Effects • Runny nose or nasal congestion • Headache • Sore throat

    39. 2004 Vaccine Shortage – Dose Sparing Administration • Half of US influenza supply lost to contamination • Study of 100 healthy adults randomized to full dose IM vs intradermal of 1/5 standardized IM dose influenza vaccine • Intradermal injection elicited same or better immunogenicity than standard IM full dose. • Kenny, RT et al Dose Sparing with Intradermal Injection of Influenza Vaccine NEJM 2004; 351: 2295-301

    40. Annual Influenza vaccination can provide some protection against severe illness even if not well matched to circulating strains. - CDC

    41. Antiviral Therapy

    42. Adamantane Class • Amantadine and Rimantadine • Historically effective for influenza A only • Inhibits M2 protein and inhibit virus uncoating • When resistance not prevalent • Effective in shortening clinical illness by one day if administered within two days of illness onset. • 70-90% effective for preventing influenza A illness when used as prophylaxis.

    43. Amantadine and Rimantadine Side Effects • Nervousness, anxiety, insomnia, lightheadedness with both medications but more significant with Amantadine • Delirium, hallucinations and seizures with higher doses but uncommon. • Fewer CNS side effects in elderly with Rimantadine • Anorexia and nausea 1-3% of population

    44. Bad News for 2005-2006 and Beyond • Adamantane class no longer recommended for treatment or prophylaxis until susceptibility re-established. • 2006 national H3N2 resistance 92% • 2005 national resistance 6% • Point mutation

    45. Neuraminidase Inhibitors • Zanamivir & Oseltamivir • Effective against influenza A & B • Reduce severity and duration of illness when started within two days of symptom onset • Treatment duration 5 days • May be used for prophylaxis 70-90% effective in preventing influenza • Consider for use in those at hight risk for complications