Influenza Treatment and Prophylaxis Guidelines for The
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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 ............................................................................................. -
Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza
Debate Regarding Oseltamivir Use for Seasonal and Pandemic Influenza Aeron Hurt WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Australia www.influenzacentre.org NA inhibitor antiviral drugs Top view of NA NA inhibitor NA enzyme active site The NA inhibitors Oseltamivir Zanamivir - Oral, IV(?) - Inhaled, IV(?) - Global - Global Peramivir Laninamivir -IV - Inhaled (single) - Japan, - Japan S.Korea, China, US The NA inhibitors Oseltamivir Zanamivir - Oral, IV(?) - Inhaled, IV(?) - Global - Global • Came on the market in many countries in 2000 after clinical studies had been conducted among influenza virus–infected patients with uncomplicated illness. • Oseltamivir is market leader ……due to ease of oral administration • Use for seasonal influenza mainly in Japan and US • With human infections of highly pathogenic influenza A(H5N1) virus from 2003 with a high case‐fatality risks of >50%, governments began to consider antiviral drug administration as a key component of their pandemic response • suitable vaccines would not be available Stockpiling for a pandemic • Oseltamivir was simpler (oral) administration than zanamivir (inhalation) and because of systemic effect of oseltamivir was expected to be appropriate for treatment of highly pathogenic viruses • Oseltamivir was suddenly in high demand! • Roche had warned that need to stockpile to guarantee availability • Since 2005, governments of middle‐income and high‐income countries around the world have spent billions of dollars (estimated) stockpiling oseltamivir (US Gov. Accounting Office). 2009 A(H1N1)pdm09 pandemic • The first pandemic of the 21st century occurred unexpectedly in 2009 after the global spread of a novel virus—influenza A(H1N1)pdm09—of swine (rather than avian) origin. -
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. -
Treatment and Prevention of Pandemic H1N1 Influenza
Annals of Global Health VOL. 81, NO. 5, 2015 ª 2015 The Authors. Published by Elsevier Inc. ISSN 2214-9996 on behalf of Icahn School of Medicine at Mount Sinai http://dx.doi.org/10.1016/j.aogh.2015.08.014 REVIEW Treatment and Prevention of Pandemic H1N1 Influenza Suresh Rewar, Dashrath Mirdha, Prahlad Rewar Rajasthan, India Abstract BACKGROUND Swine influenza is a respiratory infection common to pigs worldwide caused by type Ainfluenza viruses, principally subtypes H1N1, H1N2, H2N1, H3N1, H3N2, and H2N3. Swine influenza viruses also can cause moderate to severe illness in humans and affect persons of all age groups. People in close contact with swine are at especially high risk. Until recently, epidemiological study of influenza was limited to resource-rich countries. The World Health Organization declared an H1N1 pandemic on June 11, 2009, after more than 70 countries reported 30,000 cases of H1N1 infection. In 2015, incidence of swine influenza increased substantially to reach a 5-year high. In India in 2015, 10,000 cases of swine influenza were reported with 774 deaths. METHODS The Centers for Disease Control and Prevention recommend real-time polymerase chain reaction as the method of choice for diagnosing H1N1. Antiviral drugs are the mainstay of clinical treatment of swine influenza and can make the illness milder and enable the patient to feel better faster. FINDINGS Antiviral drugs are most effective when they are started within the first 48 hours after the clinical signs begin, although they also may be used in severe or high-risk cases first seen after this time. -
Influenza Virus-Related Critical Illness: Prevention, Diagnosis, Treatment Eric J
Chow et al. Critical Care (2019) 23:214 https://doi.org/10.1186/s13054-019-2491-9 REVIEW Open Access Influenza virus-related critical illness: prevention, diagnosis, treatment Eric J. Chow1,2, Joshua D. Doyle1,2 and Timothy M. Uyeki2* Abstract Annual seasonal influenza epidemics of variable severity result in significant morbidity and mortality in the United States (U.S.) and worldwide. In temperate climate countries, including the U.S., influenza activity peaks during the winter months. Annual influenza vaccination is recommended for all persons in the U.S. aged 6 months and older, and among those at increased risk for influenza-related complications in other parts of the world (e.g. young children, elderly). Observational studies have reported effectiveness of influenza vaccination to reduce the risks of severe disease requiring hospitalization, intensive care unit admission, and death. A diagnosis of influenza should be considered in critically ill patients admitted with complications such as exacerbation of underlying chronic comorbidities, community-acquired pneumonia, and respiratory failure during influenza season. Molecular tests are recommended for influenza testing of respiratory specimens in hospitalized patients. Antigen detection assays are not recommended in critically ill patients because of lower sensitivity; negative results of these tests should not be used to make clinical decisions, and respiratory specimens should be tested for influenza by molecular assays. Because critically ill patients with lower respiratory tract disease may have cleared influenza virus in the upper respiratory tract, but have prolonged influenza viral replication in the lower respiratory tract, an endotracheal aspirate (preferentially) or bronchoalveolar lavage fluid specimen (if collected for other diagnostic purposes) should be tested by molecular assay for detection of influenza viruses. -
Influenza: Diagnosis and Treatment
Influenza: Diagnosis and Treatment David Y. Gaitonde, MD; Cpt. Faith C. Moore, USA, MC; and Maj. Mackenzie K. Morgan, USA, MC Dwight D. Eisenhower Army Medical Center, Fort Gordon, Georgia Influenza is an acute viral respiratory infection that causes significant morbidity and mortality worldwide. Three types of influ- enza cause disease in humans. Influenza A is the type most responsible for causing pandemics because of its high susceptibility to antigenic variation. Influenza is highly contagious, and the hallmark of infection is abrupt onset of fever, cough, chills or sweats, myalgias, and malaise. For most patients in the outpatient setting, the diagnosis is made clinically, and laboratory con- firmation is not necessary. Laboratory testing may be useful in hospitalized patients with suspected influenza and in patients for whom a confirmed diagnosis will change treatment decisions. Rapid molecular assays are the preferred diagnostic tests because they can be done at the point of care, are highly accurate, and have fast results. Treatment with one of four approved anti-influenza drugs may be considered if the patient presents within 48 hours of symptom onset. The benefit of treatment is greatest when antiviral therapy is started within 24 hours of symptom onset. These drugs decrease the duration of illness by about 24 hours in otherwise healthy patients and may decrease the risk of serious complications. No anti-influenza drug has been proven superior. Annual influenza vaccination is recommended for all people six months and older who do not have contraindications. (Am Fam Physician. 2019; 100:online. Copyright © 2019 American Academy of Family Physicians.) Published online November 11, 2019 BEST PRACTICES IN INFECTIOUS DISEASE Influenza is an acute respiratory infection caused by a negative-strand RNA virus of the Orthomyxoviridae fam- Recommendations from the Choosing ily. -
Case Report Prolonged Shedding of Amantadine- and Oseltamivir- Resistant Influenza A(H3N2) Virus with Dual Mutations in an Immunocompromised Infant
Antiviral Therapy 2010 15:1059–1063 (doi: 10.3851/IMP1657) Case report Prolonged shedding of amantadine- and oseltamivir- resistant influenza A(H3N2) virus with dual mutations in an immunocompromised infant Guillermo Ruiz-Carrascoso1*, Inmaculada Casas1, Francisco Pozo1, Marta González-Vincent2, Pilar Pérez-Breña1 1Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain 2Hospital Infantil Universitario Niño Jesús, Madrid, Spain *Corresponding author e-mail: [email protected] In this study, we report a case of multidrug-resistant contained the substitutions E119V in neuraminidase and influenza A(H3N2) virus isolated from an immunosup- V27A in M2, which produce resistance to oseltamivir and pressed patient with prolonged viral shedding. We also adamantanes, respectively. This is the first report of this describe the genetic characterization of the haemagglu- dual mutation pattern in multidrug-resistant influenza tinin, neuraminidase and M2 influenza genes. The virus A(H3N2) virus. Introduction Influenza, which causes significant morbidity and daily because of neurological toxicity). After receiving mortality in immunocompromised patients, is often fludarabine and melphalan as conditioning therapy, he associated with prolonged viral shedding [1,2] underwent allogenic non-identical peripheral blood regardless of vaccination and antiviral therapy. The transplantation from his mother in May 2005 (day 0). multidrug-resistant influenza viruses, including pan- Total lymphocyte cell (TLC) count prior to transplan- demic A(H1N1) and seasonal A(H1N1) and A(H3N2), tation was 1,340 cells/mm3 (25%). On day 10, fever as reported to date in treated immunocompromised was observed and oxygen therapy was required because patients [1,3–6], have presented the E119V, R292K or of respiratory insufficiency. -
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. -
Development and Effects of Influenza Antiviral Drugs
molecules Review Development and Effects of Influenza Antiviral Drugs Hang Yin, Ning Jiang, Wenhao Shi, Xiaojuan Chi, Sairu Liu, Ji-Long Chen and Song Wang * Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences (College of Bee Science), Fujian Agriculture and Forestry University, Fuzhou 350002, China; [email protected] (H.Y.); [email protected] (N.J.); [email protected] (W.S.); [email protected] (X.C.); [email protected] (S.L.); [email protected] (J.-L.C.) * Correspondence: [email protected] Abstract: Influenza virus is a highly contagious zoonotic respiratory disease that causes seasonal out- breaks each year and unpredictable pandemics occasionally with high morbidity and mortality rates, posing a great threat to public health worldwide. Besides the limited effect of vaccines, the problem is exacerbated by the lack of drugs with strong antiviral activity against all flu strains. Currently, there are two classes of antiviral drugs available that are chemosynthetic and approved against influenza A virus for prophylactic and therapeutic treatment, but the appearance of drug-resistant virus strains is a serious issue that strikes at the core of influenza control. There is therefore an urgent need to develop new antiviral drugs. Many reports have shown that the development of novel bioactive plant extracts and microbial extracts has significant advantages in influenza treat- ment. This paper comprehensively reviews the development and effects of chemosynthetic drugs, plant extracts, and microbial extracts with influenza antiviral activity, hoping to provide some refer- ences for novel antiviral drug design and promising alternative candidates for further anti-influenza drug development. -
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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 -
Development of Effective Anti-Influenza Drugs: Congeners and Conjugates – a Review Jiun-Jie Shie1 and Jim-Min Fang2,3*
Shie and Fang Journal of Biomedical Science (2019) 26:84 https://doi.org/10.1186/s12929-019-0567-0 REVIEW Open Access Development of effective anti-influenza drugs: congeners and conjugates – a review Jiun-Jie Shie1 and Jim-Min Fang2,3* Abstract Influenza is a long-standing health problem. For treatment of seasonal flu and possible pandemic infections, there is a need to develop new anti-influenza drugs that have good bioavailability against a broad spectrum of influenza viruses, including the resistant strains. Relenza™ (zanamivir), Tamiflu™ (the phosphate salt of oseltamivir), Inavir™ (laninamivir octanoate) and Rapivab™ (peramivir) are four anti-influenza drugs targeting the viral neuraminidases (NAs). However, some problems of these drugs should be resolved, such as oral availability, drug resistance and the induced cytokine storm. Two possible strategies have been applied to tackle these problems by devising congeners and conjugates. In this review, congeners are the related compounds having comparable chemical structures and biological functions, whereas conjugate refers to a compound having two bioactive entities joined by a covalent bond. The rational design of NA inhibitors is based on the mechanism of the enzymatic hydrolysis of the sialic acid (Neu5Ac)-terminated glycoprotein. To improve binding affinity and lipophilicity of the existing NA inhibitors, several methods are utilized, including conversion of carboxylic acid to ester prodrug, conversion of guanidine to acylguanidine, substitution of carboxylic acid with bioisostere, and modification of glycerol side chain. Alternatively, conjugating NA inhibitors with other therapeutic entity provides a synergistic anti-influenza activity; for example, to kill the existing viruses and suppress the cytokines caused by cross-species infection. -
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.