Reducing the Risk: Advanced Influenza Treatment Options for the 2020-2021 Season
Learning Objectives • Identify patients at high risk for complications 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 2
Epidemiology and Burden of Seasonal Influenza in the US • Annual Estimates by the CDC From 10 Influenza Rates of serious illness and death Seasons (2010-2011 through 2019-2020)* from seasonal influenza are highest in persons >65 years, in 9.3 to 45 million illnesses children <2 years, and in anyone with medical conditions at increased risk for complications 14.2 to 21 million outpatient medical visits • During the 2017-2018 flu season, influenza is estimated to have 140,000 to 810,000 hospitalizations killed 61,000 people in the United States, more than any other year since 2010 12,000 to 61,000 deaths *Data for 2017-2018, 2018-2019, 2019-2020 are preliminary estimates. Centers for Disease Control and Prevention. cdc.gov/flu/about/burden/index.html. Accessed Nov 2, 2020; Centers for Disease Control and Prevention. gis.cdc.gov/GRASP/Fluview/FluHospRates.html. Accessed Nov 2, 2020; Rolfes MA, et al. Influenza Other Respir Viruses. 2018;12:132-137. 3
Pneumonia, Influenza, and COVID-19 Mortality: 2017-2020 28 18,000 Number of influenza coded deaths 26 Number of COVID-19 coded deaths 16,000 24 % of All Deaths Due to PIC % of deaths due to PIC 22 14,000 Number of Deaths Seasonal baseline 20 Epidemic threshold 12,000 18 16 10,000 14 Epidemic Threshold 8000 12 10 6000 8 4000 6 4 2000 Seasonal baseline 2 0 0 40 50 10 20 30 40 50 10 20 30 40 50 10 20 30 40 50 10 20 30 40 2017 2018 2019 2020 MMWR Week COVID-19 = Coronavirus disease 2019; PIC = pneumonia, influenza, or COVID-19. 4 Centers for Disease Control and Prevention. www.cdc.gov/flu/weekly/overview.htm#anchor_1539281356004. Accessed Nov 2, 2020.
Pandemics: Influenza and COVID-19 Common Name Year Virus Estimated No. of Deaths 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 2020 SARS-CoV-2 2,342,648* (by Jan 1, 2021) *Projected as of Oct 2, 2020. Dawood FS, et al. Lancet Infect Dis. 2012;12:687-695; Johns Hopkins University & Medicine. coronavirus.jhu.edu/map.html. Accessed Nov 2, 2020; Johnson NP, et al. Bull Hist Med. 2002;76:105-115; Saunders-Hastings PR, et al. Pathogens . 2016;5:66; Simonsen L, et al. PLoS Med. 2013;10:e1001558; Taubenberger JK, et al. Emerg Infect Dis. 2006;12:15-22; University of Washington Institute for Health Metrics and Evaluations. 5 covid19.healthdata.org/global?view=total-deaths&tab=trend. Accessed Nov 2, 2020.
Influenza Virus • The family Orthomyxoviridae has 3 genera, or types, Hemagglutinin NA NA Hemagglutinin that infect humans: influenza viruses A, B, and C NS 2 NS2 • Influenza A virus subtypes are based on specific HA and NA glycoproteins that they express − 18 HAs (H1-H18) Lipid Lipid − 11 NAs (N1-N11) bilayer bilayer − Potential for 144 HA and NA combinations (some HAs and NAs cannot work together) Ion Ion • Birds are reservoir for 16 HA and 9 NA subtypes channel channel Matrix Matrix protein protein Negative-sense HA = hemagglutinin; NA = neuraminidase; NS = nonstructural protein; RNA = ribonucleic acid; ss = single stranded. ssRNA 6 Clancy S. Nature Education . 2008;1:83; Vemula SV, et al. Viruses. 2016;8:96.
Case Study: Victor, a 55-Year-Old Male of Hispanic and Native-American Descent • Victor visits your primary care practice in November for an annual checkup • Height: 5 ft 8 in • Weight: 265 lb (BMI = 40.3 kg/m 2 ) • Blood pressure: 132/79 mm Hg (controlled with medication) • Unvaccinated against influenza and skeptical about the vaccine ⎻ He received the vaccine last year and “got the flu” the day after • You recommend influenza vaccination, but he refuses 7 7
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 • Certain types of cancer (lymphoma and leukemia) and cancer weeks postpartum survivors • American Indians/Alaska Natives • Chronic lung disease (eg, COPD, cystic fibrosis) • Residents of nursing homes and other • Diabetes long-term care facilities • Kidney disorders • Liver disorders • Morbid obesity (BMI ≥40 kg/m 2 ) • <19 years of age and on long-term aspirin- or salicylate-containing medications • Compromised immune system or on immunosuppressive therapies 8 Centers for Disease Control and Prevention . cdc.gov/flu/highrisk/index.htm. Accessed Nov 2, 2020.
Influenza Vaccines: 2020-2021 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 IIV4 high dose IM Prefilled syringe Egg based † ≥65 years IIV4 standard dose with IM Prefilled syringe MF59 adjuvant 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. Grohskopf LA, et al. MMWR Recomm Rep. 2020;69:1-24. 9
Vaccine Composition: 2020-2021 Influenza Season Egg-based influenza vaccines (ie, vaccines Cell culture-based inactivated (ccIIV4) and other than ccIIV4 and RIV4) will contain HA recombinant (RIV4) influenza vaccines will derived from: contain HA derived from: Influenza A/Guangdong-Maonan/SWL1536/2019 Influenza A/Hawaii/70/2019 (H1N1)pdm09-like (H1N1)pdm09-like virus virus Influenza A/Hong Kong/2671/2019 (H3N2)-like Influenza A/Hong Kong/45/2019 (H3N2)-like virus virus Influenza B/Washington/02/2019 (Victoria Influenza B/Washington/02/2019 (Victoria lineage)-like virus lineage)-like virus Influenza B/Phuket/3073/2013 (Yamagata Influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus (for quadrivalent vaccines only) lineage)-like virus ACIP = Advisory Committee on Immunization Practices. 10 Grohskopf LA, et al. MMWR Recomm Rep . 2020;69:1-24.
Case Study (cont’d): Victor • Returns to your office in early December after sudden onset of symptoms the previous morning ⎻ Fever (101.8 ° F), chills, body aches, intense headache, extreme fatigue, cough • Missed work today and yesterday • Several coworkers have been sick with flu-like illness • Influenza and COVID-19 are highly prevalent in the community • 3 days earlier, Victor babysat his 4-year-old grandson who was having some head congestion and coughing • Wife, aged 57 years, has not been vaccinated 11 11 11
Influenza Symptoms and Clinical Course • • Classic flu Complications – – Abrupt onset of fever, chills, myalgia, Sinusitis, otitis media headache, fatigue, nonproductive cough, – Pneumonia — primary viral or secondary bacterial sore throat, rhinitis – Coinfections with other bacterial/viral pathogens – Some people may have GI symptoms – Exacerbation of underlying medical conditions (eg, nausea, diarrhea) (eg, COPD, asthma, cystic fibrosis, diabetes) – Typically resolves within 3 to 7 days – Associations with cardiovascular events (eg, MI, – Cough, malaise can persist for >2 weeks stroke), parotitis • Mild illness without fever may also occur • Atypical presentations may occur in elderly, immunocompromised hosts, infants MI = myocardial infarction. Centers for Disease Control and Prevention. cdc.gov/flu/symptoms/symptoms.htm. Accessed Nov 2, 2020; Kwong JC, et al. N Engl J Med . 2018;378:345-353; Rolfes MA, et al. Clin Infect Dis . 2018;67:485-492; Uyeki TM, et al. Clin Infect Dis . 2019;68:895-902. 12
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