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Influenza A Virus Structure

NS 2. Lipid Bilayer. NA (Neuraminidase). HA (Hemagglutinin). M 2 (Ion channel). M 1 (Matrix protein). Infected cell protein NS 1. PB1, PB2, PA (Transcriptase complex). NP (Nucleocapsid). Influenza A Virus Structure. Natural History of Influenza Viruses. Serum antibody prevalence

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Influenza A Virus Structure

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  1. NS2 Lipid Bilayer NA (Neuraminidase) HA (Hemagglutinin) M2 (Ion channel) M1 (Matrix protein) Infected cell proteinNS1 PB1, PB2, PA(Transcriptase complex) NP (Nucleocapsid) Influenza A Virus Structure

  2. Natural History of Influenza Viruses Serum antibody prevalence Virus isolation B H3N8 H3N2 H2N? H2N2 H1N1 H1N1 1880 1890 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 Topley and Wilson’s Microbiology and Microbial Infections. 9th ed, Vol 1, Virology. Mahy and Collier, eds, 1998, Arnold, page 387, with permission.

  3. Hemagglutinin Subtypes of Influenza A Virus Subtype Human Swine Horse Bird H1 H2 H3 H4 H5 H6 H7 H8 H9 H10 H11 H12 H13 H14 H15 Adapted from Levine AJ. Viruses. 1992;165, with permission.

  4. Influenza Type A (H1N1) • Cause of 1918-1919 pandemic (swine) • Antigenic drift and subsequent epidemics • Disappeared in 1957 with appearance of H2N2 virus • Reappeared as the “Russian flu” in 1977 • Immunity in persons born before 1950 CDC. Influenza Prevention and Control. Available at: http://www.cdc.gov/ncidod/diseases/flu/fluinfo.htm.

  5. NEJM, June 2009

  6. Novel H1N1 Weekly Surveillance Pattern: 2008-09 Through July 11, 2009 New Slide: Needs to be regularly updated CDC: http://www.cdc.gov/flu/weekly/weeklyarchives2008-2009/WhoLab27.htm. Accessed July 30, 2009. 6

  7. Origins of Novel H1N1 Influenza First described in April 2009 in Southern California and Mexico By May 2009 had spread to 43 countries >12,000 hospitalizations >90 deaths As of September 11, 2009 >277,000 cases worldwide At least 3200+ deaths New Slide Trifonov V. N Engl J Med.2009; 361:115-119. WHO. http://www.who.int/csr/don/2009_09_11/en/index.html. Accessed September 11, 2009. 7

  8. WHO Definitions Epidemic: human-to-human spread of the virus into at least two countries in one WHO region Pandemic: human-to-human spread of the virus with community level outbreaks in at least one other country in a different WHO region than initial epidemic Attack rate: numbers of cases of infection per unit of population Virulence: severity of illness caused by a particular virus New Slide WHO. http://www.who.int/csr/disease/avian_influenza/phase/en. Accessed July 28, 2009. Gallaher WR. Virology Journal. 2009, 6:51 doi:10.1186/1743-422X-6-51. 8

  9. Pandemic Severity Categories New Slide Monto AS. Clin Infect Dis. 2009;48:S20–25. 9

  10. US Hospitalization Rate per 100,000 Population by Age Group Through July 2009 Fiore A. Presentation to Advisory Committee on Immunization Practices (ACIP). July 29,2009. 10

  11. Cross-reactive Antibody to Novel H1N1 Influenza Serum samples taken before and after vaccination with the 2005-06, 2006-07, 2007-08, or 2008-09 influenza season vaccines Before vaccination cross-reactive antibody to the novel H1N1 virus seen in: Children <18 years = 0% 18-64 years = 6%-9% >60 years = 33% Seasonal influenza vaccine did not elicit antibody response to novel H1N1 New Slide CDC. Morbid Mortal Weekly Report. May 22, 2009. 58(19);521-524. 11

  12. Inoculation Oseltamivir Treatment: Antiviral Effect in Adults Viral Titres Effect of Oral Oseltamivir Treatment on Vital Titers in Nasal Lavages Following Experimental Influenza A/Texas/36/91(H1N1) Infection Drug Administration 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 Placebo Median log10 Tissue Culture-Infective Dose per Millimeter Oseltamivir -36 -24 -12 0 12 24 36 48 60 72 84 96 108 120 132 144 156 Time, hours The viral titer area under the curve value was lower in the combined oseltamivir group (n=56) compared with placebo (n=13); P=0.02. Treanor JJ. JAMA. 2000;283:1016-1024. Hayden FG. JAMA. 1999;282:1240-1246.

  13. Oseltamivir Treatment for Influenza: Adults (16 to 65 Years) Time to Resolution of All Flu Symptoms 21 hours** 32 hours* *P<0.001; **P=0.004. Treatment initiated within 36 hours of onset of symptoms. Treanor JJ. JAMA. 2000;283:1016-1024.

  14. 12 Health Status Activity ** 10 2.8d * 8 1.9d 6 4 2 0 Placebo(n=129) Oseltamivir75 mg bid(n=124) Placebo(n=129) Oseltamivir75 mg bid(n=124) Effects of Oseltamivir on Return to Normal Activities Time to Return to Normal Health and Activity Days *P<0.001; **P=0.02. Treatment initiated within 36 hours of onset of symptoms. Treanor JJ. JAMA. 2000;283:1016-1024.

  15. Antiviral Treatment Recommendations New Slide 15 • Treatment with oseltamivir or zanamivir is recommended for: • All patients requiring hospitalization • Patients at increased risk of complications • Children 0-4 years • Pregnant women • Persons with immune suppression, chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological (including sickle cell disease), neurologic, neuromuscular, or metabolic disorders (including diabetes mellitus) or > 65 years • Early treatment is key • Clinicians should not wait for confirmatory tests to treat • Postexposure prophylaxis should generally not be used • Consider for high-risk person with close unprotected exposure • Do not use if more than 48 hours after exposure

  16. Inactivated Vaccine Effectiveness by Age and Risk Group *Effectiveness may be lower when vaccine and circulating strains antigenically different. Source: CDC.

  17. 70 14 60 12 50 10 40 8 30 6 20 4 10 2 0 0 1950 1954 1958 1962 1966 1972 1976 1980 1984 1988 1992 1996 2000 Impact of Vaccination of Japanese School Children on Mortality in the Elderly Mandatory vaccination Japan, pneumonia and influenza Japan, all cause US,pneumoniaand influenza Excess Deaths Attributed to Pneumonia and Influenza(per 100,000 population) Excess Deaths From All Causes (per 100,000 population) US, allcause Reichert TA. N Engl J Med. 2001;344:889-896.

  18. Host and Lineage Origins For The Gene Segments of 2009 A(H1N1) Virus New Slide Garten RJ. Science. 2009;325:197-201. 18

  19. Approved Monovalent Vaccines for Novel H1N1 Influenza New Slide CDC. http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Post-MarketActivities/LotReleases/ucm181956.htm. Accessed Sept. 28, 2009. 19

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