2020 Symposia Series 2
Weighing the Options: Prevention and Management of Influenza in Patients at High Risk for Complications
Learning Objectives • Identify available and emerging options for prevention of influenza • Select influenza treatment for adult patients at high risk of complications based on current recommendations and evidence • Individualize influenza treatment in pediatric patients based on current recommendations 3
Epidemiology and Burden of Seasonal Influenza in the US Burden of Influenza: Annual Estimates by the CDC From 9 Influenza Seasons (2010-2011 through 2018-2019)* • Rates of serious illness and death from 9.3 to 45 million illnesses caused seasonal influenza are highest in persons >65 years, in children <2 years, and in anyone with medical conditions at increased risk for 14.2 to 21 million outpatient medical visits complications • In the 2017-2018 flu season, influenza killed and hospitalized more people in the US than 140,000 to 810,000 hospitalizations any other year since 2010 12,000 to 61,000 deaths *Data for 2017-2018 and 2018-2019 are preliminary estimates. Centers for Disease Control and Prevention. cdc.gov/flu/about/burden/index.html. Accessed Apr 5, 2020; Centers for Disease Control and Prevention. 4 gis.cdc.gov/GRASP/Fluview/FluHospRates.html. Accessed Apr 5, 2020; Rolfes MA, et al. Influenza Other Respir Viruses. 2018;12:132-137.
Influenza-Positive Tests Reported to CDC: National Summary, 2019-2020 Season 4000 3500 Number of Positive Specimens 3000 2500 2000 1500 1000 500 0 2019-40 2019-42 2019-44 2019-46 2019-48 2019-50 2019-52 2020-02 2020-04 2020-06 2020-08 2020-10 2020-12 2020-14 2020-16 2020-18 2020-20 Week B (Yamagata Lineage) B (Victoria Lineage) B (lineage not performed) A (H3N2) A (H1N1)pmd09 A (subtyping not performed) Centers for Disease Control and Prevention. cdc.gov/flu/weekly/index.htm. Accessed Apr 5, 2020. 5
16000 Number of Specimens Tested and Percent Positive 15000 for SARS-CoV-2 14000 13000 12000 11000 10000 9000 B (Yamagata Lineage) B (Victoria Lineage) SARS-CoV-2 8000 B (lineage not performed) A (H3N2) 7000 A (H1N1)pmd09 A (subtyping not performed) 6000 5000 4000 4000 3000 3000 2000 2000 1000 1000 0 2019-40 2019-42 2019-44 2019-46 2019-48 2019-50 2019-52 2020-02 2020-04 2020-06 2020-08 2020-10 2020-12 2020-14 2020-16 2020-18 2020-20 SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. Centers for Disease Control and Prevention. cdc.gov/coronavirus/2019-ncov/covid-data/covidview/index.html. Accessed Apr 5, 2020. 6
Outpatient Visits for Influenza-like Illness Reported to CDC: National Summary, 2009-2020 9 2018-19 season 2017-18 season 8 2015-16 season 2014-15 season 7 2011-12 season % of Visitors for ILI 2009-10 season 6 2019-20 National Baseline 2019-20 season 5 4 3 2 1 0 40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 Week ILI = influenza-like Illness. Centers for Disease Control and Prevention. cdc.gov/flu/weekly/index.htm. Accessed Apr 5, 2020. 7
Influenza Pandemics Common Name Year Virus Estimated No. of Deaths (range) Spanish flu 1918 H1N1 50 million-100 million Asian flu 1958 H2N2 1 million-2 million Hong Kong flu 1968 H3N2 500,000-2 million H1N1 pandemic 2009 H1N1 151,700-575,400 COVID-19 pandemic estimate (for comparison to influenza pandemics) COVID-19 2020 SARS-CoV-2 201,129* (by Oct 1, 2020) *As of June 16, 2020; COVID-19 = Coronavirus disease 2019. Dawood FS, et al. Lancet Infect Dis. 2012;12:687-695; Johnson NP, et al. Bull Hist Med. 2002;76:105-115; Saunders-Hastings PR, et al. Pathogens . 2016;5:e66; Simonsen L, et al. PLoS Med. 2013;10:e1001558; Taubenberger JK, et al. Emerg Infect Dis. 2006;12:15-22; COVID-19 Dashboard by the Center for Systems Science and Engineering at Johns Hopkins University. coronavirus.jhu.edu/map.html. Accessed May 11, 2020; University of Washington Institute for Health Metrics and Evaluations. covid19.healthdata.org/united-states-of-america. Accessed June 16, 2020. 8
Influenza Virus NA Hemagglutinin • The family Orthomyxoviridae has 3 genera, or NS 2 types, that infect humans: influenza viruses A, B, and C • Influenza A virus subtypes are based on Lipid specific HA and NA glycoproteins that they bilayer express − 18 HAs (H1-H18) Ion − 11 NAs (N1-N11) channel − Potential for 144 HA and NA combinations (some HAs and NAs cannot work together) Matrix protein • Birds are reservoir for 16 HA and 9 NA Negative-sense subtypes ssRNA HA = hemagglutinin; NA = neuraminidase; NS = nonstructural protein; ss = single stranded. Clancy S. Nature Education . 2008;1:83; Vemula SV, et al. Viruses. 2016;8:96. 9
Case Study: Joanne, a 52-year-old female • Joanne visits your primary care practice in November for an annual checkup • She is 5 ft 6 in; 249 lb (BMI = 40.2 kg/m 2 ) • Her blood pressure is 128/78 mm Hg • Unvaccinated against influenza and skeptical about the vaccine ⎻ She received the vaccine last year and “got the flu” the day after • You recommend influenza vaccination, but she refuses 10 10
Focus on Patients at Higher Risk for Influenza Complications Demographic factors Chronic Medical Conditions • Adults aged ≥65 years • Asthma • • Children <5 years (highest risk in children Neurologic and neurodevelopmental conditions <2 years, especially if <6 months) • Blood disorders (eg, sickle cell disease) • Pregnant women (and women up to 2 weeks • Chronic lung disease (eg, COPD, cystic fibrosis) postpartum) • Diabetes • American Indians/Alaska Natives • Kidney disorders • Residents of nursing homes and other • Liver disorders long-term care facilities • Morbid obesity (BMI ≥40 kg/m 2 ) • <19 years and on long-term aspirin- or salicylate- containing medications • Compromised immune system or on immunosuppressive therapies Centers for Disease Control and Prevention . cdc.gov/flu/highrisk/index.htm. Accessed Apr 5, 2020. 11
Influenza Vaccination: Effective but Underutilized • Most effective means of preventing seasonal influenza virus infection – Recommended in all persons ≥6 months in the United States • 38% to 61% of population gets vaccinated* • Because of changes in circulating influenza strains, vaccine reformulated every year • Vaccination can prevent serious illness ⎻ CDC estimates that during the 2018-2019 season, flu vaccine prevented an estimated: • 4.4 million illnesses • 2.3 million medical visits; 58,000 hospitalizations • 35,000 deaths *Estimated from percentage of patients with acute respiratory illness who were vaccinated for the 2019-2020 flu season. Dawood FS, et al. MMWR Morb Mortal Wkly Rep. 2020;69:177-182. 12
Interim Data for Influenza Vaccine Effectiveness During the 2019-2020 Season • Vaccination does not guarantee protection • Interim data for vaccine effectiveness during 2019-2020 flu season (adjusted): – 55% against influenza B/Victoria – 37% against influenza A(H1N1)pdm09 – 45% overall effectiveness against influenza A and B combined • Despite overall vaccine effectiveness of 38% in 2017-2018 season, flu vaccine prevented: ‒ 7.1 million illnesses, 3.7 million medical visits ‒ 109,000 hospitalizations, 8000 deaths 13 Dawood FS, et al. MMWR Morb Mortal Wkly Rep 2020;69:177-182; Grohskopf LA, et al. MMWR Recomm Rep. 2019;68:1-21. 13
Influenza Vaccines: 2019-2020 Influenza Season Manufacturing Process Age Indication Route Formulations Egg based † ≥6 months IIV4 standard dose IM Prefilled syringe, MDV* ≥4 years IIV4 standard dose Cell culture based IM Prefilled syringe, MDV* Egg based † ≥65 years IIV3 high dose IM Prefilled syringe Egg based † ≥65 years IIV3 standard dose with IM Prefilled syringe MF59 adjuvant ≥18 years RIV4 Recombinant HA IM Prefilled syringe LAIV4 ‡ Egg based † 2 to 49 years Intranasal Single-use intranasal spray *MDV = multidose vials containing ≤25 ug/0.5 mL thimerosal; † Contraindicated only if history of severe allergic reaction (eg, anaphylaxis) to egg; ‡ Precautions in individuals with asthma, or underlying medical conditions that may predispose to complications after wild-type influenza infection; IIV3 = inactivated influenza vaccine, trivalent; IIV4 = inactivated influenza vaccine, quadrivalent; IM = intramuscular; LAIV4 = Live attenuated influenza vaccine; RIV4 = recombinant influenza vaccine, quadrivalent. 14 Grohskopf LA, et al. MMWR Recomm Rep. 2019;68:1-21.
ACIP Guideline Update for 2019-2020 Influenza Season • Vaccine composition: ‒ A/Brisbane/02/2018 (H1N1) pdm09-like virus ‒ A/Kansas/14/2017 (H3N2)-like virus ‒ B/Colorado/06/2017-like virus (B/Victoria/2/87 lineage) ‒ B/Phuket/3073/2013-like virus (B/Yamagata/16/88 lineage) [quadrivalent only] • Clinicians may administer any licensed, age-appropriate influenza vaccine to all patients ‒ Includes those with egg allergy, except for history suggestive of anaphylaxis ACIP = Advisory Committee on Immunization Practices. Grohskopf LA, et al. MMWR Recomm Rep . 2019;68:1-21. 15
Influenza Vaccination in Children Aged 6 Months Through 8 Years Has the child received ≥2 doses of influenza vaccine previously (excluding the current influenza season)? No or don’t know Yes 2 doses of 2019-2020 1 dose of 2019-2020 influenza vaccine influenza vaccine (≥4 weeks apart) Grohskopf LA, et al. MMWR Recomm Rep. 2019;68:1-21. 16
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