Expert Opinion on Neuraminidase Inhibitors for the Prevention and Treatment of Influenza

Total Page:16

File Type:pdf, Size:1020Kb

Expert Opinion on Neuraminidase Inhibitors for the Prevention and Treatment of Influenza SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza Review of recent systematic reviews and meta-analyses www.ecdc.europa.eu ECDC SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza – review of recent systematic reviews and meta-analyses This report of the European Centre for Disease Prevention and Control (ECDC) was coordinated by Pasi Penttinen and Kari Johansen. Contributing authors Emmanuel Robesyn, Eeva Broberg, Piotr Kramarz Acknowledgements Expert group: Barbara Michiels (University of Antwerp); Kari S. Lankinen (Finnish Medicines Agency); Regine Lehnert (German Federal Agency for Drugs and Medical Devices); Darina O’Flanagan (Health Protection Surveillance Centre Ireland); Anders Tegnell (Public Health Agency of Sweden); Johan Giesecke (Karolinska Institutet); Peter Horby (University of Oxford); John Watson (UK Department of Health); Angela Campbell (US Centers for Disease Control and Prevention); Frederick Hayden (University of Virginia School of Medicine); Filip Josephson (Medical Products Agency of Sweden) Observers: Manuela Mura (European Medicines Agency); Nikki Shindo (World Health Organization); Caroline Brown (World Health Organization Regional Office for Europe) Presenters external to expert group: Arnold Monto (University of Michigan School of Public Health); Jonathan Nguyen-Van-Tam (University of Nottingham) ECDC representatives: Mike Catchpole; Piotr Kramarz; Pasi Penttinen; Angus Nicoll; Kari Johansen; Emmanuel Robesyn; Eeva Broberg; René Snacken; Cornelia Adlhoch; Brenna Deckert; Luciana Muresan Suggested citation: European Centre for Disease Prevention and Control. Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza – review of recent systematic reviews and meta-analyses. Stockholm: ECDC; 2017. Stockholm, August 2017 ISBN 978-92-9498-080-9 doi: 10.2900/01723 Catalogue number TQ-02-17-871-EN-N © European Centre for Disease Prevention and Control, 2017 Reproduction is authorised, provided the source is acknowledged ii SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza Contents Abbreviations ............................................................................................................................................... iv Glossary ........................................................................................................................................................ v Executive summary ........................................................................................................................................ 1 Background ................................................................................................................................................... 3 Methods ........................................................................................................................................................ 6 Results and discussion .................................................................................................................................... 8 General characteristics of the systematic reviews and meta-analyses reviewed by ECDC expert group .............. 8 Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children ...................... 8 Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials ...................... 9 Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A(H1N1)pdm09 virus infection ............................................................................................................... 9 Additional publications reviewed .......................................................................................................... 10 Treatment of outpatients ......................................................................................................................... 11 Safety ................................................................................................................................................ 11 Efficacy .............................................................................................................................................. 11 Treatment of inpatients ....................................................................................................................... 14 Post-exposure prophylaxis ................................................................................................................... 15 Pre-exposure and seasonal prophylaxis ................................................................................................. 17 Limitations in evidence base .................................................................................................................... 18 Remaining gaps in the current knowledge base .............................................................................................. 20 Efficacy and effectiveness against severe outcomes in previously healthy individuals .................................... 20 Efficacy and effectiveness in risk groups ................................................................................................... 20 Efficacy and effectiveness against emerging zoonotic and pandemic influenza strains ................................... 20 Cost-effectiveness in primary care and hospital use ................................................................................... 20 Options for recommendations in EU/EEA Member States ................................................................................. 21 Recommendations for further public health research to strengthen current evidence and preparedness for future pandemics ................................................................................................................................................... 30 Observational studies assessing current neuraminidase inhibitors. ............................................................... 30 New antivirals ......................................................................................................................................... 30 Antivirals in combination therapy .............................................................................................................. 30 Strengths and limitations of methodology ....................................................................................................... 31 References .................................................................................................................................................. 32 Figures Figure 1. Consumption of neuraminidase inhibitors (ATC group J05AH) in the community and hospital sector in Europe (reporting year 2013). ......................................................................................................................... 5 Figure 2. Survival by time to treatment .......................................................................................................... 15 Tables Table 1. Emergence of novel localised influenza infections/epidemics and pandemics in the 20th and 21st centuries ...... 3 Table 2. Recommended dosage and schedule of neuraminidase inhibitors for treatment and chemoprophylaxis in the EU/EEA ................................................................................................................................................... 4 Table 3. Primary and secondary outcomes used in the 2014 analyses by Jefferson et al. ...................................... 8 Table 4. Comparison of trials on treatment of adults included in the Jefferson et al. and Dobson et al. analyses ..... 9 Table 5. Clinical groups deemed to be at risk of developing influenza-related complications ................................ 13 Table 6. ECDC Expert opinion on options for public health recommendations on treatment and prophylaxis of influenza with neuraminidase inhibitors .......................................................................................................... 23 iii Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza SCIENTIFIC ADVICE Abbreviations CDC United States Centers for Disease Control and Prevention CFR Case–fatality ratio COPD Chronic obstructive pulmonary disease CI Confidence interval DDD Daily defined dose ECDC European Centre for Disease Prevention and Control EC European Commission EMA European Medicines Agency ESAC-net European Surveillance for Antimicrobial Consumption network HCW Healthcare worker HR Hazard ratio ICU Intensive care unit ILI Influenza-like illness ITT Intention to treat ITT-I Intention to treat – infected MUGAS Multiparty Group for Advice on Science NAI Neuraminidase inhibitor PRIDE Post-pandemic review of anti-influenza drug effectiveness PCR Polymerase chain reaction RCT Randomised clinical trial/randomised controlled trial RR Relative risk RT-PCR Reverse transcriptase PCR iv SCIENTIFIC ADVICE Expert opinion on neuraminidase inhibitors for the prevention and treatment of influenza Glossary Accelerated failure-time model A model for survival analysis that models the relation between exposure (or treatment) and survival time. Advisory Forum The Advisory Forum advises the Director of the Centre on the quality of the scientific work undertaken by ECDC. It is composed of senior representatives of national
Recommended publications
  • Dectova, INN-Zanamivir
    28 February 2019 EMA/CHMP/851480/2018 Committee for Medicinal Products for Human Use (CHMP) Assessment report DECTOVA International non-proprietary name: zanamivir Procedure No. EMEA/H/C/004102/0000 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 An agency of the European Union © European Medicines Agency, 2019. Reproduction is authorised provided the source is acknowledged. Table of contents 1. Background information on the procedure .............................................. 7 1.1. Submission of the dossier ...................................................................................... 7 1.2. Steps taken for the assessment of the product ......................................................... 9 2. Scientific discussion .............................................................................. 12 2.1. Problem statement ............................................................................................. 12 2.1.1. Disease or condition ......................................................................................... 12 2.1.2. Epidemiology .................................................................................................. 12 2.1.3. Biologic features .............................................................................................
    [Show full text]
  • Antiviral Agents Active Against Influenza a Viruses
    REVIEWS Antiviral agents active against influenza A viruses Erik De Clercq Abstract | The recent outbreaks of avian influenza A (H5N1) virus, its expanding geographic distribution and its ability to transfer to humans and cause severe infection have raised serious concerns about the measures available to control an avian or human pandemic of influenza A. In anticipation of such a pandemic, several preventive and therapeutic strategies have been proposed, including the stockpiling of antiviral drugs, in particular the neuraminidase inhibitors oseltamivir (Tamiflu; Roche) and zanamivir (Relenza; GlaxoSmithKline). This article reviews agents that have been shown to have activity against influenza A viruses and discusses their therapeutic potential, and also describes emerging strategies for targeting these viruses. HXNY In the face of the persistent threat of human influenza A into the interior of the virus particles (virions) within In the naming system for (H3N2, H1N1) and B infections, the outbreaks of avian endosomes, a process that is needed for the uncoating virus strains, H refers to influenza (H5N1) in Southeast Asia, and the potential of to occur. The H+ ions are imported through the M2 haemagglutinin and N a new human or avian influenza A variant to unleash a (matrix 2) channels10; the transmembrane domain of to neuraminidase. pandemic, there is much concern about the shortage in the M2 protein, with the amino-acid residues facing both the number and supply of effective anti-influenza- the ion-conducting pore, is shown in FIG. 3a (REF. 11). virus agents1–4. There are, in principle, two mechanisms Amantadine has been postulated to block the interior by which pandemic influenza could originate: first, by channel within the tetrameric M2 helix bundle12.
    [Show full text]
  • Efficacy of Baloxavir Marboxil on Household Transmission Of
    Umemura et al. Journal of Pharmaceutical Health Care and Sciences (2020) 6:21 https://doi.org/10.1186/s40780-020-00178-4 RESEARCH ARTICLE Open Access Efficacy of baloxavir marboxil on household transmission of influenza infection Takumi Umemura1,2* , Yoshikazu Mutoh2, Takato Kawamura1, Masayuki Saito1, Takahito Mizuno1, Aiko Ota1, Koji Kozaki1, Tetsuya Yamada1, Yoshiaki Ikeda3 and Toshihiko Ichihara2 Abstract Background: Baloxavir marboxil (baloxavir) is a new anti-influenza virus agent that is comparable to oseltamivir phosphate (oseltamivir). Since the efficacy of baloxavir in preventing household transmission of influenza is not well established, we compared the secondary household influenza virus transmission rates between patients on baloxavir vs oseltamivir. Methods: Between October 2018 and March 2019, we enrolled index patients (diagnosed with influenza and treated with baloxavir or oseltamivir) and household members. The secondary attack rate of household members was compared between index patients treated with baloxavir vs oseltamivir. Risk factors of household transmission were determined using multivariate logistic analyses. Results: In total, 169 index patients with influenza type A were enrolled. The median age was 27.0 (interquartile range; 11–57) years. The number of index patients treated with baloxavir and oseltamivir was 49 and 120, respectively. The secondary attack rate was 9.0% (95% confidence interval [CI]: 4.6–15.6) in the baloxavir group and 13.5% (95% CI: 9.8–17.9) in the oseltamivir group. In the multivariate analysis, independent risk factors were 0–6 years of age (odds ratio [OR] 2.78, 95% CI: 1.33–5.82, p < 0.01) and not being on baloxavir treatment.
    [Show full text]
  • Summary of Neuraminidase Amino Acid Substitutions Associated with Reduced Inhibition by Neuraminidase Inhibitors
    Summary of neuraminidase amino acid substitutions associated with reduced inhibition by neuraminidase inhibitors. Susceptibility assessed by NA inhibition assays Source of Type/subtype Amino acid N2 b (IC50 fold change vs wild type [NAI susceptible virus]) viruses/ References Comments substitutiona numberinga Oseltamivir Zanamivir Peramivir Laninamivir selection withc A(H1N1)pdm09 I117R 117 NI (1) RI (10) ? ?d Sur (1) E119A 119 NI/RI (8-17) RI (58-90) NI/RI (7-12) RI (82) RG (2, 3) E119D 119 RI (25-23) HRI (583-827) HRI (104-286) HRI (702) Clin/Zan; RG (3, 4) E119G 119 NI (1-7) HRI (113-1306) RI/HRI (51-167) HRI (327) RG; Clin/Zan (3, 5, 6) E119V 119 RI (60) HRI (571) RI (25) ? RG (5) Q136K/Q 136 NI (1) RI (20) ? ? Sur (1) Q136K 136 NI (1) HRI (86-749) HRI (143) RI (42-45) Sur; RG; in vitro (2, 7, 8) Q136R was host Q136R 136 NI (1) HRI (200) HRI (234) RI (33) Sur (9) cell selected D151D/E 151 NI (3) RI (19) RI (14) NI (5) Sur (9) D151N/D 151 RI (22) RI (21) NI (3) NI (3) Sur (1) R152K 152 RI(18) NI(4) NI(4) ? RG (3, 6) D199E 198 RI (16) NI (7) ? ? Sur (10) D199G 198 RI (17) NI (6) NI (2) NI (2) Sur; in vitro; RG (2, 5) I223K 222 RI (12–39) NI (5–6) NI (1–4) NI (4) Sur; RG (10-12) Clin/No; I223R 222 RI (13–45) NI/RI (8–12) NI (5) NI (2) (10, 12-15) Clin/Ose/Zan; RG I223V 222 NI (6) NI (2) NI (2) NI (1) RG (2, 5) I223T 222 NI/RI(9-15) NI(3) NI(2) NI(2) Clin/Sur (2) S247N 246 NI (4–8) NI (2–5) NI (1) ? Sur (16) S247G 246 RI (15) NI (1) NI (1) NI (1) Clin/Sur (10) S247R 246 RI (36-37) RI (51-54) RI/HRI (94-115) RI/HRI (90-122) Clin/No (1)
    [Show full text]
  • View Full Issue
    Volume 31, Issue 2, December 2015 ISSN 0204-8809 ACTA MICROBIOLOGICA BULGARICA Bulgarian Society for Microbiology Union of Scientists in Bulgaria Acta Microbiologica Bulgarica The journal publishes editorials, original research works, research reports, reviews, short communications, letters to the editor, historical notes, etc from all areas of microbiology An Official Publication of the Bulgarian Society for Microbiology (Union of Scientists in Bulgaria) Volume 31 / 2 (2015) Editor-in-Chief Angel S. Galabov Press Product Line Sofia Editor-in-Chief Angel S. Galabov Editors Maria Angelova Hristo Najdenski Editorial Board I. Abrashev, Sofia S. Aydemir, Izmir, Turkey L. Boyanova, Sofia E. Carniel, Paris, France M. Da Costa, Coimbra, Portugal E. DeClercq, Leuven, Belgium S. Denev, Stara Zagora D. Fuchs, Innsbruck, Austria S. Groudev, Sofia I. Iliev, Plovdiv A. Ionescu, Bucharest, Romania L. Ivanova, Varna V. Ivanova, Plovdiv I. Mitov, Sofia I. Mokrousov, Saint-Petersburg, Russia P. Moncheva, Sofia M. Murdjeva, Plovdiv R. Peshev, Sofia M. Petrovska, Skopje, FYROM J. C. Piffaretti, Massagno, Switzerland S. Radulovic, Belgrade, Serbia P. Raspor, Ljubljana, Slovenia B. Riteau, Marseille, France J. Rommelaere, Heidelberg, Germany G. Satchanska, Sofia E. Savov, Sofia A. Stoev, Kostinbrod S. Stoitsova, Sofia T. Tcherveniakova, Sofia E. Tramontano, Cagliari, Italy A. Tsakris, Athens, Greece F. Wild, Lyon, France Vol. 31, Issue 2 December 2015 ACTA MICROBIOLOGICA BULGARICA CONTENTS Review Articles Biohydrometallurgy in Bulgaria - Achievements and
    [Show full text]
  • Journal Pre-Proof
    Journal Pre-proof Ongoing Clinical Trials for the Management of the COVID-19 Pandemic M.P. Lythgoe, P. Middleton PII: S0165-6147(20)30070-5 DOI: https://doi.org/10.1016/j.tips.2020.03.006 Reference: TIPS 1706 To appear in: Trends in Pharmacological Sciences Please cite this article as: M.P. Lythgoe and P. Middleton, Ongoing Clinical Trials for the Management of the COVID-19 Pandemic, Trends in Pharmacological Sciences (2020), https://doi.org/10.1016/j.tips.2020.03.006 This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2020 Published by Elsevier. Journal Pre-proof Ongoing Clinical Trials for the Management of the COVID-19 Pandemic *MP Lythgoe1 & *P Middleton2 1Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, W120HS, London, UK 2 Department of Metabolism, Digestion & Reproduction, Imperial College London, St Marys Hospital, Praed Street, W21NY, London UK *Equal contribution Corresponding Email: [email protected] Key words: Coronavirus, SARS-CoV-2, COVID-19, 2019-nCoV, pandemic ABSTRACT COVID-19 has rapidly developed into a worldwide pandemic causing a significant health and economic burden.
    [Show full text]
  • Oseltamivir, Zanamivir and Amantadine in the Prevention of Influenza: a Systematic Review
    Journal of Infection (2011) 62,14e25 www.elsevierhealth.com/journals/jinf Oseltamivir, zanamivir and amantadine in the prevention of influenza: A systematic review Rachel J. Jackson a,*, Katy L. Cooper a, Paul Tappenden a, Angie Rees b, Emma L. Simpson a, Robert C. Read c, Karl G. Nicholson d a Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK b School of Health and Related Research, University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK c Department of Infection & Immunity, School of Medicine, University of Sheffield, Beech Hill Rd, Sheffield, S10 2RX, UK d Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, LE2 7LX, UK Accepted 5 October 2010 Available online 13 October 2010 KEYWORDS Summary Objective: To systematically review evidence relating to the clinical efficacy of Influenza; oseltamivir, zanamivir and amantadine in the prevention of influenza. Prophylaxis; Methods: RCTs evaluating these interventions in seasonal prophylaxis and post-exposure pro- Prevention; phylaxis were identified using electronic bibliographic databases and handsearching of Amantadine; retrieved articles. Oseltamivir; Results: Oseltamivir was effective in preventing symptomatic laboratory-confirmed influenza Zanamivir; (SLCI) in seasonal prophylaxis in healthy adults and at-risk elderly subjects and in post-expo- Neuraminidase sure prophylaxis within households of mixed composition. Post-exposure prophylaxis using inhibitor; oseltamivir for paediatric contacts was observed to prevent SLCI. Zanamivir prevented M2 inhibitor; SLCI in seasonal prophylaxis in healthy adults, at-risk adults and adolescents and in post-expo- Systematic review sure prophylaxis within mixed households, with a trend for seasonal and post-exposure preven- tative effects in elderly subjects.
    [Show full text]
  • State of Connecticut-Department of Social Services
    STATE OF CONNECTICUT-DEPARTMENT OF SOCIAL SERVICES 55 FARMINGTON AVENUE, HARTFORD, CONNECTICUT 06105 Connecticut AIDS Drug Assistance Program (CADAP) Formulary Effective: March 1, 2018 Antiretroviral: Multiclass Single Tablet Regimens Abacavir/ Lamivudine/ Dolutegravir Efavirenz/Emtricitabine/ Tenofovir Disoproxil Elvitegravir/Cobicistat/ Emtricitabine/Tenofovir ( Triumeq ) Fumarate (Atripla ) Disoproxil Fumarate (Stribild ) Bictegravir/ Emtricitabine/Tenofovir Elvitegravir, Cobicistat, Emtricitabine/Tenofovir Emtricitabine/Rilpivirine/ Tenofovir Disoproxil Alafenamide (Biktarvy) Alafenamide (Genvoya ) Fumarate (Complera ) Antiretroviral: Combination Medications Abacavir /Lamivudine (Epzicom) Atazanavir/Cobicistat (Evotaz) Lamivudine/Zidovudine (Combivir) Abacavir/Lamivudine/ Zidovudine Darunavir/Cobicistat (Prezcobix) Lopinavir/Ritonavir (Kaletra) (Trizivir) Emtricitabine/Tenofovir (Truvada) Antiretrovirals: Nucleoside Reverse Transcriptase Inhibitor (NRTIs) Medications Abacavir (Ziagen) Emtricitabine (Emtriva) Tenofovir DF (Viread) Didanosine (ddI, Videx, Videx EC) Lamivudine (3TC, Epivir, Epivir HBV ) Zidovudine (AZT, Retrovir ) Stavudine (Zerit) Antiretrovirals: Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTIs) Medications Delavirdine Mesylate (Rescriptor) Etravirine (Intelence) Rilpivirine (Edurant) Efavirenz (Sustiva) Nevirapine ( Viramune/Viramune XR ) Antiretrovirals: Protease Inhibitor (PIs) Medications Atazanavir Sulfate (Reyataz) Indinavir (Crixivan) Ritonavir (Norvir) Darunavir (Prezista) Lopinavir/Ritonavir (Kaletra)
    [Show full text]
  • Peramivir (Rapivab®) National Drug Monograph March 2015
    Peramivir (RAPIVAB)Monograph Peramivir (Rapivab®) National Drug Monograph March 2015 VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives The purpose of VA PBM Services drug monographs is to provide a comprehensive drug review for making formulary decisions. Updates will be made when new clinical data warrant additional formulary discussion. Documents will be placed in the Archive section when the information is deemed to be no longer current. FDA Approval Information Description/Mechanism of Peramivir is a neuraminidase inhibitor with activity against influenza A and B Action viruses. Indication(s) Under Review in Peramivir is indicated for the treatment of acute, uncomplicated influenza in this document (may include patients 18 years and older who have been symptomatic for no more than two off label) days. Please note the prescribing information states the following limitations of use: • Efficacy based on clinical trials in which the predominant influenza virus type was influenza A; a limited number of subjects infected with influenza B virus were enrolled. • Consider available information on influenza drug susceptibility patterns and treatment effects when deciding whether to use. • Efficacy could not be established in patients with serious influenza requiring hospitalization. Dosage Form(s) Under 200mg single-use 20 mL vial (10mg/mL) for injection Review REMS REMS No REMS Postmarketing Requirements Pregnancy Rating Pregnancy Category C Executive Summary Efficacy Approval of peramivir was based upon a single pivotal Phase 2 trial, two supporting Phase 2 trials, and one supporting Phase 3 trial (refer to Table 1) evaluating adult patients with acute, uncomplicated influenza who presented within 48 hours of symptom onset; all trials were randomized, multicentered, double-blind, and placebo-controlled.
    [Show full text]
  • Influenza Antiviral Medications: Summary for Clinicians
    Influenza Antiviral Medications: Summary for Clinicians The information on this page should be considered current for the 2014-2015 influenza season for clinical practice regarding the use of influenza antiviral medications. This page contains excerpts from Antiviral Agents for the Treatment and Chemoprophylaxis of Influenza - Recommendations of the Advisory Committee on Immunization Practices (ACIP). PDF Version[1 MB, 28 pages] Antiviral medications with activity against influenza viruses are an important adjunct to influenza vaccine in the control of influenza. Influenza antiviral prescription drugs can be used to treat influenza or to prevent influenza. Four licensed prescription influenza antiviral agents are available in the United States. o Two FDA-approved influenza antiviral medications are recommended for use in the United States during the 2014-2015 influenza season: oral oseltamivir (Tamiflu®) and inhaled zanamivir (Relenza®). Oseltamivir and zanamivir are chemically related antiviral medications known as neuraminidase inhibitors that have activity against both influenza A and B viruses. o Amantadine and rimantadine are antiviral drugs in a class of medications known as adamantanes. These medications are active against influenza A viruses, but not influenza B viruses. As in recent past seasons, there continues to be high levels of resistance (>99%) to adamantanes among influenza A (H3N2) and influenza A (H1N1) pdm09 ("2009 H1N1") viruses. Therefore, amantadine and rimantadine are not recommended for antiviral treatment or chemoprophylaxis of currently circulating influenza A viruses. Antiviral resistance to oseltamivir and zanamivir among circulating influenza viruses is currently low, but this can change. Also, antiviral resistance can emerge during or after treatment in some patients (e.g., immunosuppressed).
    [Show full text]
  • In Vitro Activity of Favipiravir and Neuraminidase Inhibitor Combinations Against Oseltamivir-Sensitive and Oseltamivir-Resistant Pandemic Influenza a (H1N1) Virus
    Arch Virol DOI 10.1007/s00705-013-1922-1 ORIGINAL ARTICLE In vitro activity of favipiravir and neuraminidase inhibitor combinations against oseltamivir-sensitive and oseltamivir-resistant pandemic influenza A (H1N1) virus E. Bart Tarbet • Almut H. Vollmer • Brett L. Hurst • Dale L. Barnard • Yousuke Furuta • Donald F. Smee Received: 16 July 2013 / Accepted: 6 November 2013 Ó Springer-Verlag Wien (outside the USA) 2013 Abstract Few anti-influenza drugs are licensed in the favipiravir was combined with the NAIs against the osel- United States for the prevention and therapy of influenza A tamivir-sensitive influenza virus, and an additive effect and B virus infections. This shortage, coupled with contin- against the oseltamivir-resistant virus. Although the clinical uously emerging drug resistance, as detected through a global relevance of these drug combinations remains to be evalu- surveillance network, seriously limits our anti-influenza ated, results obtained from this study support the use of armamentarium. Combination therapy appears to offer sev- combination therapy with favipiravir and NAIs for treatment eral advantages over traditional monotherapy in not only of human influenza virus infections. delaying development of resistance but also potentially enhancing single antiviral activity. In the present study, we evaluated the antiviral drug susceptibilities of fourteen pan- Introduction demic influenza A (H1N1) virus isolates in MDCK cells. In addition, we evaluated favipiravir (T-705), an investigational Influenza is a highly contagious acute viral infection that drug with a broad antiviral spectrum and a unique mode of has afflicted mankind for centuries [1]. It continues to be a action, alone and in dual combination with the neuraminidase substantial source of morbidity and mortality with an inhibitors (NAIs) oseltamivir, peramivir, or zanamivir, enormous financial and socioeconomic impact [2].
    [Show full text]
  • AIRCURRENTS: Modeling a Modern- Day Spanish Flu Pandemic
    FEBRUARY 2013 AIRCURRENTS: MODELING A MODERN- DAY SPANISH FLU PanDEMIC BY NITA MADHAV, M.S.P.H. EDITED BY MOLLY J. MARKEY, PH.D. Editor’s NotE: The 1918 influenza pandemic killed tens of millions of people around the world, making it one of the deadliest infectious disease outbreaks in modern history. In this article, Nita Madhav, a Principal Analyst in AIR’s Research and Modeling Group, characterizes the historic 1918 pandemic and estimates the effects of a similar pandemic occurring today using the AIR Pandemic Flu Model (scheduled for release in Summer 2013). The 1918 “Spanish flu” pandemic was one of the greatest public health catastrophes of the past century. Although the start location THE ArticLE: Explores the effects of a is unknown, the first known cases appeared in Fort Riley, Kansas in modern-day influenza pandemic caused by a virus February of 1918. By the end of the pandemic, millions of people identical to the 1918 “Spanish flu” pathogen, and estimates worldwide had been killed. Global estimates of deaths range from the mortality rates and life insurance losses this event would 20 million to more than 100 million, at a time when the global inflict. population was approximately 1.8 billion. HIGHLIGHTS: The AIR Pandemic Flu Model reveals that the In the United States, the 1918 pandemic caused life insurance “Spanish flu” pandemic would have a much less dramatic impact losses of nearly USD 100 million (The Insurance Press, 1919), which today (in terms of mortality rates) than the actual Spanish flu corresponds to USD 19.9 billion today.1 In fact, during the seven- pandemic did in 1918.
    [Show full text]