9/8/18. Objectives. INFLUENZA: What We Need to Know. Disclosures

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1 Objectives INFLUENZA: What We Need to Know Cindy Weston, DNP, RN, CCRN, CNS-CC, FNP-BC Assistant Professor Texas A&M Describe influenza patterns and pathophysiology Discuss factors surrounding vaccination and vaccine effectiveness Explain the burden of mortality, morbidity and costs of influenza on the healthcare system Discuss strategies for nurse practitioners to improve vaccination rates, diagnosis and treatment for influenza Disclosures No Conflicts I used to HATE getting my flu shot What is you favorite book or movie that involves a viral pandemic? 1

2 Influenza Influenza The Burden of the Disease Seasonal Influenza Globally: 250,000 to 500,000 deaths each year In the United States each year: 12,000-56,000 deaths/yr 140, ,000 hospitalizations Million cases each year $37.5 billion in economic costs from influenza and pneumonia Pandemic Influenza An ever-present threat Cytokine STORM The PROBLEM Spread 24 hours before symptoms develop Viral Shed for 5-7+ days 2

3 The SPREAD SUMMER WINTER September 1, 2018 Symptoms Uncomplicated Fever Cough Sore Throat Headache Rhinorrhea Muscle aches GI: Nausea, Vomiting, Diarrhea Complicated Respiratory Shortness of breath Dyspnea Tachypnea Hypoxia CNS Encephalopathy Multiorgan Failure Renal Myocarditis Elevated LFTs Rhabdomyolysis 3

4 Uncomplicated Influenza Symptoms Adults Fever Headache Malaise Nonproductive Cough Sore Throat Rhinitis Children Otitis media N/V High Fever Duration Uncomplicated 3-7 days, but Malaise can persist > 2 weeks Complicated Pulmonary Disease Heart Disease Secondary Infections Bacterial pneumonia Sinusitus Population at Risk Influenza Pregnant Women- especially during 3 rd Trimester and up to 2 weeks postpartum Children <2 years People with : Chronic Lung Disease Asthma Cardiovascular Disease (except hypertension) Renal Hepatic Hematological (including sickle cell disease) Metabolic disorders (including diabetes mellitus); A. RNA B. DNA Influenza Virus? The Orthomyxovirus Influenza virus A Influenza virus B Influenza virus C Isavirus- (salmon) Thogotovirus (ticks to vertebrate animals) Quaranjavirus (arthropods & birds) INFLUENZA A VIRUS 4

5 What is the H & N of the Influenza Virus names? Hemagglutinin (H) Viral surface- receptor to bind to host cell 17 subtypes- H1, H2, H3 H5 H17 Elicits the immune response- best part of the vaccine!! Neuraminidase (N) Viral surface-enzyme that lets virus into host cell 10 subtypes- N1, N2.N10 Also part of the vaccine NOMENCLATURE A/HongKong/4801/2014 (H3N2) like virus Virus type Geographic origin Strain number Year of isolation Virus Sub-type Season AUSTRALIA Spring

6 So how is strain coverage determined for the annual vaccine? Trivalent/Quadrivalent 3 viral coverage (2-As; 1-B strain) 4 viral coverage (Trivalent + another B-strain) Vaccine Efficacy Influenza Vaccine A/Michigan/45/2015 (H1N1)pdm09-like virus, A/Singapore/INFIMH /2016 (H3N2)-like virus, B/Colorado/06/2017-like (B/Victoria lineage) virus. Quadrivalent vaccines, B/Phuket/3073/2013-like (B/Yamagata lineage) virus Vaccine Sources Embryonated Hen s Eggs Inactivated Live Mammalian Cell Cultures Purified Recombinant HA made in insect cells Vaccine Manufacturers Sanofi Pasteur (Fluzone- quadrivalent; Fluzone HD age 65 and up; Flublok-age 18 & up- recombinant) GlaxoSmithKline (Fluarix/Flulaval- quadrivalent) Seqirus USA, Inc (Afluria age 5 & up/flucelvax age 4 and up cell-culture- quadrivalent) AstraZeneca (FluMist age 2-49 years- quadrivalent) 6

7 Prices EVERYONE ages 6 months & UP! 6 months-8 years need 2 doses 1 month apart the 1 st time! Age > 65 recommend HD (24.2% more effective) Egg allergy- can get vaccine under monitoring OR get recombinant vaccine (FluBlock) Contraindications for Immunization U.S. Peak Influenza Activity through Seasons Age < 6 months Prior allergic reaction (anaphylaxis) Guillian-Barre Syndrome within 6 weeks TIMING OF IMMUNIZATION DEBUNK The Myths! 7

8 The Flu Vaccine gives you the Flu! I got the vaccine last year and I still Got the Flu! Is it worth getting the vaccine? Which test? When do we test? How do we test? This Flu Season to test or not to test? What does it all mean? Now What? To treat or not to treat? POSITIVE FLU! Which of the Following Anti-Influenza Agents Does NOT cover Influenza B A. Amantadine B. Oseltamivir C. Rimantadine D. Zanamivir early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0 48; 95% CI ; <0 0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0 50; 95% CI ; p<0 0001). Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0 81; 95% CI ; p=0 0024) E. A&C 8

9 Anti-Influenza Agents Adamantine Antivirals Amantadine Rimantadine Antiviral activity A only A only Dosing 100mg BID 100mg BID Bioavailability >90% >90% Half-life hrs hrs Protein Binding 67% 40% Metabolism <10% 75% Renal Excretion >90% 25% Dose Adjustments ClCr<50ml/min ClCr<30ml/min CDC does not recommend for use in US! From: Chapter 58. Antiviral Agents (Nonretroviral) Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12e, 2011 Replicative cycles of DNA (A) and RNA (B) viruses. The replicative cycles of herpesvirus (A) and influenza (B) are examples of DNAencoded and RNA-encoded viruses, respectively. Sites of action of antiviral agents also are shown. Key: mrna = messenger RNA; cdna = complementary DNA; vrna = viral RNA; DNAp = DNA polymerase; RNAp = RNA polymerase; crna = complementary RNA. The symbol indicates a block to virus growth. A. Replicative cycles of herpes simplex virus, a DNA virus, and the of early genes involved in genome replication, such as thymidine kinases, DNA polymerases, etc. After DNA replicatioprobable sites of action of antiviral agents. Herpesvirus replication is a regulated multistep process. After infection, a small number of immediate-early genes are transcribed; these genes encode proteins that regulate their own synthesis and are responsible for synthesis n, the bulk of the herpesvirus genes (called late genes) are expressed and encode proteins that either are incorporated into or aid in the assembly of progeny virions. B. Replicative cycles of influenza, an RNA virus, and the loci for effects of antiviral agents. The mammalian cell shown is an airway epithelial cell. The M2 protein of influenza virus allows an influx of hydrogen ions into the virion interior, which in turn promotes dissociation of the RNP (ribonuclear protein) segments and release into the cytoplasm (uncoating). Influenza virus mrna synthesis requires a primer cleared from cellular mrna and used by the viral RNAp complex. The neuraminidase inhibitors zanamivir and oseltamivir specifically inhibit release of progeny virus. Small capitals indicate virus proteins. Legend: Date of download: 11/4/2014 Copyright 2014 McGraw-Hill Education. All rights reserved. Anti-Influenza Agents Neuraminidase Inhibitors Mechanism of Action of Neuraminidase Inhibitors Oseltamivir Zanamivir Peramivir Antiviral activity A & B A & B A&B Dosing 75mg BID 2 Inhalations (10mg) BID 600mg IV X 1 over min Bioavailability 80% <5% 100% Half-life 6-10 hrs hrs 20 hrs Protein Binding 3% <10% < 30% Renal Excretion 95% 100% 90% Dose Adjustments ClCr<30 None CrCl <30 Moscona A. N Engl J Med 2005;353: Complications Conditions Associated with an Increased Risk of Complications with the Flu Pneumonia ARDS Cytokine Storm Oxygenation ECMO Hypotension Vasopressors 9

10 To Treat or Not to Treat that is the question. The art of medicine consists in amusing the patient while nature affects the cure. Voltaire Treatment in Pregnancy 1 st Trimester 2 nd Trimester 3 rd Trimester L&D Post-partum Supportive Care Treatment Anti-pyretics Antihistamines Steroids- inhaled vs. systemic Decongestants Anti-tussives Antibiotics Planning Assumptions: Health Care 50% or more of those who become ill will seek medical care Number of hospitalizations and deaths will depend on the virulence of the pandemic virus Moderate (1957-like) Severe (1918-like) Illness 90 million (30%) 90 million (30%) Outpatient 45 million (50%) 45 million (50%) Hospitalization 865, million ICU care 128, million Mechanical Ventilation 64, ,500 Deaths 209, million FUTURE for FLU Summary Debunk Myths Prevention is KEY! Flu Vaccine Early Treatment- Neuraminidase Inhibitors Identify High Risk Populations In May 2018, NIH launched a Phase 2 clinical trial of a universal influenza vaccine called M-001. The vaccine, which was developed and produced by BiondVax Pharmaceuticals based in Ness Ziona, Israel, contains antigenic peptide sequences shared among many different influenza strains. 10

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