National Center for Immunization & Respiratory Diseases Update on Influenza Vaccines, the 2017 2018 Influenza Season, and the Impact of Vaccination on Influenza Disease Burden Melissa Rolfes, PhD MPH Epidemiologist Influenza Division, Centers for Disease Control and Prevention First Coast Infectious Disease Symposium (FCID) February 2, 2018 1
Outline Background on influenza virus infections Influenza vaccines National influenza vaccination coverage and effectiveness 2017 2018 influenza season in the United States Influenza disease burden Impact of influenza vaccination on disease burden 2
Background on Influenza Virus Infections
Influenza Viruses Influenza A viruses Cause seasonal epidemics and periodic pandemics in humans H1N1pdm09 H3N2 Influenza B viruses Victoria Yamagata 4
Influenza Virus Infections Influenza is a highly contagious respiratory illness Clinical illness: Acute onset fever, chills, body aches, fatigue, cough, pharyngitis, rhinitis Influenza-like-illness (ILI) Fever ( 100 o F) Cough or sore throat 5
Complications from Influenza Virus Infection Severe illness and complications can result in hospitalization, admission to the ICU, or death Primary influenza complications or secondary bacterial infections People at risk for flu complications: 6
Influenza Testing Rapid antigen test Molecular assays Immunofluorescent assays Viral culture Serological assays 7
Treatment for Influenza Virus Infection CDC recommends antiviral treatment for: 8
Treatment for Influenza Virus Infection CDC recommends antiviral treatment for: Treatment should not be delayed while test results are pending 9
Influenza Vaccines
Prevention of Influenza Influenza vaccine is our best tool to prevent influenza virus infection Current vaccines use killed hemagglutinin protein of virus Vaccine-induced antibodies block hemagglutinin from binding to respiratory cells Influenza vaccines are recommended for all persons aged 6 months Best time to receive vaccine is prior to widespread influenza virus circulation (ideally by October) However, vaccination is recommended as long as influenza viruses are circulating in the community 11
There are Many Influenza Vaccines 12
Inactivated Recombinant Live-attenuated 13
Trivalent Inactivated Quadrivalent Recombinant Live-attenuated 14
High-dose Inactivated Standard-dose Recombinant Live-attenuated 15
Inactivated Adjuvanted Recombinant Live-attenuated 16
Inactivated Cell-culture propagated virus * Non-egg based Recombinant * Non-egg based Live-attenuated 17
Influenza Viruses Mutate at a High Rate Influenza virus replication is prone to errors Provides an advantage; viruses are able to escape immune pressures Rapid evolutions requires constant updates to vaccine composition 18
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WHO Influenza Vaccine Virus Selection Twice annually, experts convene to choose viruses in the influenza vaccine February meeting for Northern Hemisphere vaccine September meeting for Southern Hemisphere vaccine Gather and analyze international virus surveillance data and vaccine effectiveness data Viruses are chosen to best represent what is and will be circulating in each hemisphere 20
Influenza Vaccine Components Northern Hemisphere (selected in February 2017 for the 2017/18 season) an A/Michigan/45/2015 (H1N1)pdm09-like (change from 2016/17) an A/Hong Kong/4801/2014 (H3N2)-like a B/Brisbane/60/2008-like (B/Victoria lineage) B/Phuket/3073/2013-like (B/Yamagata lineage; in quadrivalent) Southern Hemisphere (selected in September 2017 for the 2018 season) an A/Michigan/45/2015 (H1N1)pdm09-like an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like (change from NH) a B/Phuket/3073/2013-like (B/Yamagata lineage; change from NH) a B/Brisbane/60/2008-like (B/Victoria lineage; in quadrivalent) 21
National Influenza Vaccination Coverage and Effectiveness
Influenza Vaccination Coverage
National Influenza Vaccination Coverage 24 National Immunization Survey-Flu (NIS-Flu) and Behavioral Risk Factor Surveillance System (BRFSS). Error bars represent the 95% confidence interval. Starting with the 2011-12 season, adult estimates reflect changes in BRFSS survey methods
Influenza Vaccination Coverage Children 25
Influenza Vaccination Coverage Adults 26
Influenza Vaccination Coverage Healthcare Personnel, November 2017 Other clinical personnel includes allied health professionals, dentists, technicians, technologists, emergency medical technicians, and paramedics. 27
Influenza Vaccination Among Healthcare Personnel Place of work, November 2017 ǁ Other setting includes dental offices, pharmacies, emergency medical service locations, and other health care settings. 28
Influenza Vaccination Among Healthcare Personnel By employer policy, November 2017 29
Influenza Vaccine Effectiveness 30
Influenza Vaccine Effectiveness United States Annual estimates of influenza vaccine effectiveness (VE) Based on observational studies conducted at 6 sites Sites enroll starting with flu circulation (Dec/Jan) through March/April VE against outpatient medically-attended influenza (every season from 2004 2017) 31
10 19 PERCENT EFFECTIVE 21 37 39 41 47 49 48 52 52 56 60 Seasonal Influenza Vaccine Effectiveness Outpatient medically-attended influenza 70 60 50 40 30 20 10 0 2004-05 2005-06 2006-07 2007-08 2008-09 2009-10 2010-11 2011-12 2012-13 2013-14 2014-15 2015-16 2016-17 FLU SEASON 32
10 19 PERCENT EFFECTIVE 21 37 39 41 47 49 48 52 52 56 60 Seasonal Influenza Vaccine Effectiveness Outpatient medically-attended influenza 70 60 50 40 30 20 10 0 2004-05 2005-06 2006-07 2007-08 2008-09 2009-10 2010-11 2011-12 2012-13 2013-14 2014-15 2015-16 2016-17 FLU SEASON 33
Influenza Vaccine Effectiveness outpatient setting by influenza virus subtype Influenza virus type/subtype Pooled VE estimate Pooled 95% confidence interval A/H3N2 33% 26 39% A/H1N1pdm09 61% 57 65% B 54% 46 61% Belongia EA, et al., The Lancet Infectious Diseases, 2016; 16(8) 34
Vaccine effectiveness (%) Vaccine effectiveness against influenza A/B in inpatient 1 and outpatient 2 setting 2016-17 season 100 80 60 40 20 30 30 23 19 31 42 37 25 0-20 INPATIENT OUTPATIENT 18 years 18 years INPATIENT OUTPATIENT 18-49 years 18-49 years INPATIENT OUTPATIENT 50-64 years 50-64 years INPATIENT OUTPATIENT 65 years 65 years 1 Multivariate logistic regression models adjusted for site, age group, sex, race/ethnicity, days from illness onset to specimen collection, calendar time of illness onset, home oxygen use, frailty, and number of hospitalizations in past year 2 Multivariate logistic regression models adjusted for site, age, sex, race/ethnicity, self-rated general health status, days from onset to specimen collection, and calendar time of illness onset 35
Influenza Vaccination Effectiveness Against Pediatric Death Recent studied aimed at estimating VE against influenza-confirmed death in children 1 Study included all reported pediatric flu deaths in the US from 2010 2014 Compared influenza vaccination coverage in deaths compared with coverage among nationally-representative pediatric cohorts Stratified by presence of high-risk conditions 2 VE against influenza death, overall 65% (95% CI: 54 74%) Children with high-risk condition: 51% (95% CI: 31 67%) Children without high-risk condition: 65% (95% CI: 47 78%) 1 Flannery B, et al., Pediatrics, 2017; 139 (5) 2 High-risk conditions included asthma, chronic lung disease, neurologic or neurodevelopmental disorders, heart disease (including congenital heart disease), blood disorders, endocrine disorders, metabolic disorders, kidney disorders, liver disorders, immunosuppression, and pregnancy 36
2017 2018 US Influenza Season * Current as of January 27, 2018
FoxBusiness Miami Herald LA Times
Is this season really as bad as this? And how does CDC track the flu? Flu season reaches epidemic status each season in the US CDC uses several surveillance systems Clinical laboratories (proportion of flu tests positive) State public health laboratories (types/subtypes of viruses) Outpatient visits for influenza-like-illness (ILI) Influenza-associated hospitalization Vital statistics records on pneumonia and influenza coded deaths Pediatric laboratory-confirmed influenza deaths Weekly summaries are viewable online on FluView (www.cdc.gov/flu/weekly/) 39
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Flu really has been everywhere, all at once
Influenza Disease Burden
Burden of Influenza in the United States Rates and percentages from flu surveillance do not quantify the extent and burden of disease CDC developed mathematical model to translate surveillance rates into national numbers of illnesses and hospitalizations 1 Estimates generated after each influenza season Posted online: https://www.cdc.gov/flu/about/disease/burden.htm 48 1. Reed C, Chaves SS, Daily Kirley P, et al. Estimating influenza disease burden from population-based surveillance data in the United States. PLoS One 2015; 10(3): e0118369.
Burden of Influenza Hospitalizations Approximate 5-season range: 140,000 710,000 Outpatient medical visits 4.3 16.7 million Symptomatic community illness 9.2 35.6 million
Burden of Influenza: 2016 2017 season Age (yrs) Illnesses (in millions) Outpatient medical visits (in millions) Hospitalizations <5 2.32 1.56 16,200 5--17 6.15 3.20 16,900 18--49 8.90 3.29 50,000 50--64 8.87 3.81 94,100 65 4.65 2.60 423,000 All ages 30.9 million (9.6% of US population) 14.5 million 600,000 50
Impact of Vaccination on Disease Burden
Burden averted by seasonal influenza vaccination Use the estimated risk to calculate hypothetical counts of each outcome assuming no influenza vaccination Expected number of flu-related hospitalization Expected number of flu-related outpatient medical visit Hospitalizations Medical visits Illness Expected number of flu-related illness 52
Burden averted by seasonal influenza vaccination Prevented Observed Expected number of flu-related hospitalization Expected number of flu-related outpatient medical visit Hospitalizations Medical visits Illness Expected number of flu-related illness 53
Burden Prevented by Vaccination: 2010 2017 Season Illnesses (in millions) Medical visits (in millions) Hospitalizations No. Fraction prevented (%) 2010-11 5.0 2.5 71,000 20.8 2011-12 2.0 1.0 39,000 22.7 2012-13 5.6 2.7 62,500 11.1 2013-14 6.7 3.1 87,000 21.5 2014-15 1.6 0.8 47,000 7.5 2015-16 5.1 2.5 72,000 18.9 2016-17* 5.3 2.6 85,000 12.4 * Preliminary estimates 54
Substantial additional impact by improving vaccine coverage/effectiveness Improving coverage 5% point increase (e.g. 64% coverage in kids and 48% coverage in adults) Prevent an additional 500,000 illnesses and 7,000 hospitalizations Improving effectiveness 5% point increase (e.g. 44% VE overall) Prevent an additional 500,000 illnesses and 12,000 hospitalizations 55
Conclusions
Conclusions Influenza viruses cause respiratory illnesses resulting in substantial numbers of illnesses in the US each season Influenza antiviral treatment can reduce symptoms and risk of complications Think flu and treat as appropriate Influenza can be severe and place substantial burden on hospitals
Conclusions, continued 2017/18 season has been widespread and intense throughout the country Several more week or months of flu activity are anticipated Influenza vaccine is the single best way to prevent against influenza It is not too late to get vaccinated Despite modest effectiveness and coverage, vaccination prevents millions of illnesses and thousands of hospitalizations each season Increasing vaccine coverage and effectiveness would have measurably large impact on reducing influenza burden 58
Thank you! Melissa Rolfes, PhD, MPH mrolfes1@cdc.gov For more information, contact CDC 1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Complications from Influenza Virus Infection Severe illness and complications can result in hospitalization, admission to the ICU, or death Primary influenza complications or secondary bacterial infections People at risk for flu complications: Children aged <5 years (esp. aged <2 years) Adults aged 65 years Pregnant women People living in long-term care facilities American Indians/Alaska Natives People with underlying medical conditions Asthma Neurological conditions Chronic lung disease/copd Heart disease Endocrine disorders (including diabetes) Kidney disorders Immunocompromised People with extreme obesity (BMI 40) 62
Currently Available Vaccine Products Some abbreviations IIV = Inactivated influenza vaccine LAIV = Live attenuated influenza vaccine RIV = Recombinant influenza vaccine Prefixes: SD = standard dose HD = high dose a = adjuvanted cc = cell culture-based Numeric suffixes (e.g., RIV3, IIV4) indicate trivalent or quadrivalent, respectively HA = hemagglutinin 63
Inactivated (IIV) vs. Recombinant (RIV) vs. Live Attenuated (LAIV) IIV (intramuscular, intradermal) 10 products: Contain inactivated virus (split or subunit) High Dose or Standard Dose; high-dose licensed only for 65 years Trivalent or quadrivalent Unadjuvanted or adjuvants; adjuvanted licensed only for 65 years Egg- or cell culture-based Many brands, some approved for those as young as 6 months of age RIV (intramuscular) 2 products: Contains recombinant HA produced in insect cell culture Egg-free Trivalent and quadrivalent both available for 2017-18 LAIV (intranasal) 1 product: Contains live attenuated virus, cold-adapted to reproduce locally Not recommended for use in 2017-18 due to concerns about effectiveness against H1N1pdm09-like viruses in the US during 2013-15 and 2015-16 64
High-dose vs. Standard-dose (IIVs Only) SD-IIV3 and SD-IIV4: Contain 15μg of HA total per virus (45μg total for trivalents and 60μg total for quadrivalents) HD-IIV3: One product, Fluzone High-Dose (Sanofi Pasteur) Licensed for 65 years Contain 60μg of HA total per virus (180μg total) High-dose only available as a trivalent Observed to provide stronger immune response (in prelicensure studies) and have greater efficacy/effectiveness in persons aged 65 years 65
Unadjuvanted or adjuvanted (IIVs Only) Currently licensed U.S. influenza vaccines are unadjuvanted, with one exception aiiv3 (first available in U.S. for 2016-17) One product, Fluad (Seqirus) Licensed for 65 years in the U.S. Contains MF59, an oil-in-water adjuvant Intended to provide better immune response Non-inferior response compared with IIV3 in pre-licensure studies 66
Egg-Based vs. non Egg-Based Most influenza vaccines contain viruses propagated in eggs Two exceptions: cciiv4: One product, Flucelvax Quadrivalent (Sanofi Pasteur) Licensed for 4 years Viruses are propagated in canine kidney cells rather than eggs However, some of the initial viruses supplied to the manufacturer are egg-derived (for 2017-18, only the H3N2 is cell-derived), so not considered egg-free RIV3 and RIV4: Two products, Flublok and Flublok Quadrivalent (Sanofi Pasteur/Protein Sciences) Licensed for 18 years Does not contain (and is manufactured without) influenza viruses Contains only HA, produced by introduction of HA genetic sequence into an insect cell line (Spodoptera frugiperda) using a Baculovirus vector Considered egg-free 67
Northern Hemisphere formulation Southern Hemisphere formulation 68