12/15/2014 Nothing to disclose…. Influenza Update Lisa Winston, MD UCSF / San Francisco General Hospital Divisions of Infectious Diseases and Hospital Medicine Influenza Biology Influenza Biology Influenza A Influenza viruses are single stranded, enveloped RNA viruses � 16 different HA subtypes � Divided into types A, B, ( C ) � 9 different NA subtypes � Influenza A viruses infect humans, pigs, horses, sea mammals and birds � Human influenza A viruses: H1N1, � Influenza B viruses infect humans (and seals) H1N2, H2N2, H3N2 � Two surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) used to subtype influenza A viruses 1
12/15/2014 Influenza Biology Influenza Drift and Shift Hemagglutinin attaches to cellular sialic acid receptors “Antigenic Drift” – minor changes due to Neuraminidase cleaves sialic acid releasing point mutations infectious virus particles Segmented genome with “Antigenic Shift” – major changes which 8 RNA fragments may be due to reassortment of RNA •Polymerase PB2 •Polymerase PB1 segments •Polymerase PA •Hemaglutinin � In setting of infection with 2 different •Nuclear protein viruses •Neuraminidase Trifonov et al, New Engl •Matrix proteins •Nonstructural proteins J Med, 2009;361:115-119 Pandemic Influenza Pandemics occur when little immunity to circulating virus � Potentially due to shift, recirculation of previous virus, or direct transmission from animal to human 1918 – 1919: “Spanish flu,” 20-25 million deaths; H1N1 virus 1957-1958: “Asian flu;” H2N2 virus 1968-1969: “Hong Kong flu;” H3N2 virus 2009-2010: H1N1 virus Belshe, New Engl J Med, 2005;353: 2209 - 11 2
12/15/2014 Seasonal Influenza Swine is presumed “mixing vessel” Morbidity and Mortality for 2009 H1N1 Old estimate: 36,000 deaths per year in U.S. Pigs have Severe disease in the elderly, very young, and those receptors for human and avian with significant comorbidities influenza A viruses � 90% influenza-associated deaths occur in persons 65 and older Thompson et al, JAMA 2003;289:179-86 Revised estimates of deaths associated with seasonal influenza 1976 – 2007 � Average 23,607 deaths (range 3,349 to 48,614) � When influenza A(H3N2) prominent, death rate 2.7x higher Trifonov et al, New Engl MMWR August 27, 2010 / 59(33);1057-1062 J Med, 2009;361:115-119 Novel H1N1 Epidemiology Novel H1N1 vs. Seasonal Influenza Among person 65 years and older, FIGURE. Distribution by age group of persons hospitalized with laboratory-confirmed hospitalization rates related to novel H1N1 were influenza,* --- United States, 2007--08 winter influenza season and April 15--August 11, less than 20% of those usually seen in the winter 2009 with seasonal influenza A About 2/3 of patients hospitalized have a known medical risk factor for severe disease (including pregnancy) Hospitalization among pregnant women is about 4 times higher than in the general population Obesity, especially morbid obesity, may be a Median age hospitalization: 20 years new risk factor Highest incidence of hospitalization children < 4 years Median age of persons who died: 37 years MMWR, August 28, 2009;58(RR10):1-8 MMWR, August 28, 2009;58(RR10):1-8 3
12/15/2014 Current Influenza Activity Influenza Vaccines 2014-15 Influenza Vaccine Inactivated vaccine given by injection (same as 2013-2014) � Trivalent: 2 influenza A strains, 1 influenza B strain A/California/7/2009 (H1N1)-like � Quadrivalent: 2 influenza A strains, 2 influenza A/Texas/50/2012 (H3N2)-like B strains B/Massachusetts/2/2012-like (Yamagata lineage) � Few contraindications For quadrivalent vaccine add: Severe egg allergy – risk assessment, referral � B/Brisbane/60/2008-like (Victoria lineage) Severe previous reaction MMWR 2014;63:483-90 Guillain-Barre (relative contraindication) Live attenuated intranasal vaccine (FluMist) • Nationwide this season: 82% A, 18%B � Same strains as inactivated vaccine • A almost all H3N2: 52% are different (drifted) from vaccine strain Quadrivalent • B split Yamagata and Victoria lineages 4
12/15/2014 Newest influenza vaccines Influenza Vaccine Indications licensed in U.S. All people older than 6 months � Unless there is a contraindication Three quadrivalent inactivated vaccines: 2 influenza A and 2 influenza B strains; intramuscular � Fluarix, FluLaval, Fluzone FluBlok: baculovirus expression system (recombinant), no exposure to eggs – age 18+ Flucelvax: cell culture derived (canine kidney cells) – age 18+ Afluria trivalent vaccine can be administered by jet Estimated that in the 2013-14 influenza season, vaccination injector (FDA approved August 2014 ages 18-64) prevented 7.2 million illnesses, 3.1 million medically attended illnesses, and 90,000 hospitalizations MMWR 2014;63:1151-4 High Dose Inactivated Vaccine Intradermal Influenza Vaccine Fluzone intradermal vaccine approved by FDA Fluzone High-Dose licensed for those 65 and older in 2011 Trivalent; contains 60 µ g of hemagglutinin per virus Needle is about one-tenth of standard length strain compared with 15 µ g in regular dose Contains 9 mcg hemagglutinin per strain versus Enhanced immune response in those 65 and older standard 15 mcg with high dose vs. standard dose Local reactions (mild to moderate) more common � Dose is 0.1 mL versus standard 0.5 mL with high dose vaccine J Infect Dis 2009;200:161-3 Approved ages 18 – 64 years 2-year study with 31,989 participants randomized to Local reactions are more common high dose vs. standard dose: 1.4% vs. 1.9% with confirmed influenza (relative efficacy 24.2%) New Engl J Med 2014;371:635-45. 5
12/15/2014 Live Attenuated Influenza Live Attenuated Influenza Vaccine Vaccine Who should not get LAIV? � Outside recommended age ranges Attenuated, heat sensitive and cold � Chronic medical conditions, including asthma adapted � Pregnant women Approved for healthy persons ages 2 – 49, � History of Guillain-Barre (relative including healthcare workers and contacts contraindication) of most high risk patients � Severe egg allergy – risk assessment, prefer Runny/stuffy nose is common TIV � Contact with highly immunosuppressed patients, e.g. bone marrow transplant Live Attenuated Influenza LAIV Vaccine (LAIV) Surveillance in military ages 18 – 49 over 3 influenza Efficacy seasons (2006 – 2009) � In children, 85 – 90% effective in preventing Compared influenza like illness, influenza, and influenza A compared with placebo pneumonia in those vaccinated with LAIV compared with � In children, several studies suggest better inactivated vaccine: 41,670 vaccination events efficacy than inactivated vaccine Excluded those with contraindications to LAIV � Study in adults in Michigan 2004 – 2005 Controlled for sociodemographics, occupation, influenza season: decreased efficacy compared geographic area with inactivated vaccine, especially against No differences found by vaccine group influenza B (poor matches for both influenza B and H3N2 “drifted” strain) Ohmit et al, N Engl J Med 2006;355:2513 - 22 Clin Infect Dis 2013;56:11-19 6
12/15/2014 LAIV now preferred for some Influenza Vaccination of children Healthcare Personnel Starting 2014-15, CDC now preferentially Many elderly, chronically ill, and recommends LAIV for healthy children immunocompromised persons do not have ages 2 – 8 years if no contraindications a robust immune response to the vaccine and vaccine is immediately available Influenza is transmitted in healthcare facilities � HCP both transmit and acquire influenza � HCP frequently work when they are ill � Influenza is shed before symptoms develop; some infections are asymptomatic MMWR 2014;63:691-7 Does Influenza Vaccination of HCP Help? Does Influenza Vaccination of HCP Help? HCP influenza vaccination is associated with Based on results of double blind, RCTs: decreased patient mortality in long-term care Vaccination can decrease some Potter et al, J Infect Dis 1997;175:1-6 manifestations of influenza infection and Carman et al, Lancet 2000;355:93-7 absenteeism in working adults Hayward et al, BMJ 2006;333:1241 Bridges et al, JAMA 2000;284:1655-63 Lemaitre et al, J Am Geriatr Soc 2009;57:1580-6 Nichol et al, JAMA 1999;281:137-44 Note that efficacy of vaccination varies from Vaccination decreases influenza infection year-to-year and is influenced by vaccine match in HCP and may decrease absenteeism Wilde et al, JAMA 1999;281:908-13 Saxen et al, Pediatr Infect Dis J 1999;18:779-83 7
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