Podcasts about neuraminidase

TWiV explains Guillain-Barré Syndrome associated with RSV vaccines, outbreaks of metapneumovirus in China and India, editors resign to protest Elsevier's use of AI in publishing, global distribution and diversity of wild bird associated pathogens, and broadly inhibitory anti-neuraminidase antibody from human memory B cells. Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Brianne Barker Subscribe (free): Apple Podcasts, RSS, email Become a patron of TWiV! Links for this episode Support science education at MicrobeTV ASV 2025 GBS with RSV vaccine (FDA) Increase in respiratory infections in China (ECDC) Elsevier journal editors resign (Retract Watch) Wild bird associated pathogens (Med) Broad anti-neuraminidase antibody (Cell Host Micr)   Letters read on TWiV 1185 Timestamps by Jolene. Thanks! Weekly Picks Brianne – Dear Reviewer 2 Rich – National Data Buoy Center Alan – BBC audio program on the World Morse Code Championships Vincent – These are the 20 most-studied bacteria — the majority have been ignored Listener Picks Peter – Local graffiti in Sydney Vivian – The Peoples' Hospital by Dr. Ricardo Nuila Intro music is by Ronald Jenkees Send your virology questions and comments to twiv@microbe.tv Content in this podcast should not be construed as medical advice.

Matters Microbial #60: Influenza, Epidemics, Pandemics, and Fortunate Mistakes October 9, 2024 Today, Dr. Adam Lauring of the University of Michigan joins the #QualityQuorum to discuss the job of a physician-scientist, RNA viruses, the tricks that influenza uses to create epidemics and pandemics, and the science behind flu vaccines. Host: Mark O. Martin Guest: Adam Lauring Subscribe: Apple Podcasts, Spotify Become a patron of Matters Microbial! Links for this episode A description of the MD/PhD path in science. An introduction to RNA viruses. An article describing different types of RNA viruses. The history of influenza. An overview of the influenza virus. An essay on the shift/drift issue in influenza. A more formal review of the shift/drift issue in influenza. A video about the evolution of RNA viruses. An essay about influenza virus evolution describing some of Dr. Lauring's work. Dr. Lauring and his colleague's fascinating research lab page. Dr. Lauring's faculty website. Intro music is by Reber Clark Send your questions and comments to mattersmicrobial@gmail.com

In this episode, we review the high-yield topic of⁠ ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Neuraminidase Inhibitors ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠from the Microbiology section. Follow ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Medbullets⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbullets

Elisa Fadda obtained her PhD in 2004 from the Department of Chemistry at the Université de Montréal under Professor Dennis R. Salahub. From May 2004 to May 2008, she worked as a post-doctoral fellow in Dr Régis Pomès group in Molecular Structure and Function at the Hospital for Sick Children (Sickkids) Research Institute in Toronto. From June 2008 until May 2013, Elisa worked as a research associate and honorary research lecturer in Prof Robert J. Woods group in the School of Chemistry at NUI Galway. In 2013 she was awarded a Post-Graduate Certificate in Teaching and Learning in Higher Education from the Centre for Learning and Teaching (CELT) at NUI Galway. In August 2013, Elisa became an Assistant Lecturer in the Department of Chemistry at Maynooth University, taking on a Lecturer position since 2014.You will hear the following terms used during the interview. I've included some descriptions here. Quantum chemistry -The branch of chemistry that apply quantum mechanics to chemical systems, including electronic structure, molecular dynamics and Schrödinger equations.Biophysics – And approach to science that applies methods typically used in physics to study biology and biological systems.Glycoproteins – Proteins which contain oligosaccharide chains (glycans), attached to amino acid side-chains via a covalent bond.Carbohydrates – Molecules (typically biological) composed of Carbon, Hydrogen and Oxygen, typically with a 2:1 Hydrogen:Oxygen atom ratio.Glycan (or polysaccharide) – Compounds made of many monosaccharide subunits, linked via a glycoside bond.N-Glycans – Glycans attached to a protein at an Asparagine residue via an N-glycosidic bond.Sequon – A sequence of amino acids in a protein that serve as a carbohydrate binding site.The carbohydrate is often an N-linked-Glycan.Asparagine, proline, serine, threonine. – Amino acids found naturally in biological proteins. Asparagine, serine and threonine are required in specific combinations to form a sequon, proline must be absent from a sequon.Glycosaminoglycans or mucopolysaccharides- Long, linear glucans consisting of repeating disaccharide units – most commonly uronic acid and an amino sugar.Glycosylation – A reaction in which a carbohydrate molecule is attached to a functional group of another molecule (such as a hydroxyl).  In biology the term typically refers to the carbohydrate being attached to a protein molecule.Folded protein – Proteins have several levels of structure, secondary, tertiary (and arguably quaternary) levels of structure describe how the polypeptide chain forms into specific structures that typically confer functional properties.Cryo-EM – Cryogenic Electron Microscopy studies samples cooled to cryogenic temperatures (-153 oC or lower), while embedded in vitreous water.X-Ray crystallography – A technique which uses X-rays to determine crystal structures, but studying the X-ray diffraction patterns.NMR – Nuclear Magnetic Resonance subjects samples to a strong magnetic fields and measures the resonance pattern of the nuclei. It is widely used to study the structure and dynamics of organic molecules.Spike proteins – More properly ‘Peplomers', spike proteins are glycoproteins that project from the surface of a virus particle lipid bilayer and play an important part in viral infectivity.Coronavirus – One of a group of related RNA viruses that cause respiratory tract infections in birds and mammals. These infections lead to diseases that can have mild effects, or be lethal. The Covid-19 pandemic was caused by a coronavirus, the SARS-CoV-2 virus. The 2002/4 SARS outbreak was caused by the SARS-CoV-1 virus.HIV – The Human Immunoseficiency Virus is two species of lentivirus that if left untreated cause Acquired Immunodeficiency Syndrome (AIDS) in humans.Receptor – A protein embedded in a cell membrane which binds to a specific molecule, or class of molecules.  Once the target molecule is bound, there is typically and effect within the cell to trigger some form of biological process.(viral) Pathogensis – The process by which a disease progresses. Viral pathogensis is specific to a disease caused by a virus.Computer node – Each computer in a connected cluster that are working together.GPUs – Graphics Processing Units are specific electronic circuits that rapidly address memory in order to output images to a display device. Their highly parallel structure makes them efficient at processing algorithms that process large data blocks in parallel.Glycoanalytics – Scientific study of glycosylated molecules, often biological in nature.Neuraminidase, or Sialidase – Are enzymes that cut the glycosidic bonds of neuraminic acids. This action helps viruses move through the respiratory tract mucus and infect host cells. The publication we refer to early on in the discussion is available at https://www.sciencedirect.com/science/article/pii/B9780128194751000560?via%3Dihub.  A full list of Elisa's publications is available at her group website. Elisa is contactable on social media, and you can find her on LinkedIn https://www.linkedin.com/in/elisa-fadda-a012b194/ (although, Elisa admits, she's rarely on LinkedIn)On Twitter, search @ElisaTelisaThe group website is https://efadda73.wixsite.com/elisafadda Our theme music is "Wholesome" by Kevin MacLeod (https://incompetech.com)Music from https://filmmusic.ioLicense: CC BY (http://creativecommons.org/licenses/by/4.0/) Connect with me (Paul) at https://www.linkedin.com/in/paulorange/H.E.L. group can be found at www.helgroup.com online,on LinkedIn at https://www.linkedin.com/company/hel-group/ on Twitter, we're @hel_group, https://twitter.com/hel_groupor search for us on Facebook

Au Pharmascope, on est de plus en plus confiant que l’influenza ne se pointera pas le bout du nez cette année, mais on ne prend aucune chance! Dans ce 67ème épisode, Nicolas, Sébastien et Isabelle discutent du traitement de l’influenza. Les objectifs pour cet épisode sont: Décrire les objectifs de traitement de l’influenzaIdentifier les patients qui peuvent bénéficier d’un traitement de l’influenzaExpliquer les bénéfices et les risques des traitements antiviraux contre l’influenza Ressources pertinentes en lien avec l’épisode Revue systématique et méta-analyse portant sur les traitements antivirauxJefferson T et coll. Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children. Cochrane Database Syst Rev. 2014;2014:CD008965. Étude portant sur l’oseltamivirButler CC et coll. Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial. Lancet. 2020;395:42-52. Études CAPSTONE-1 et 2 portant sur le baloxavirHayden FG et coll. Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med. 2018;379:913-23. Ison MG et coll. Early treatment with baloxavir marboxil in high-risk adolescent and adult outpatients with uncomplicated influenza (CAPSTONE-2): a randomised, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2020; 20:1204-14. Guide de l’INESSSInstitut national d’excellence en santé et en services sociaux. Guide d’usage optimal -  Traitement et prophylaxie de l’influenza chez l’enfant et l’adulte dans le contexte de la covid-19. Décembre 2020. Lignes directrices de l’IDSAUyeki TM et coll. Clinical Practice Guidelines by the Infectious Diseases Society of America: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza. Clin Infect Dis. 2019;68:e1-47. Lignes directrices canadiennesAoki FY et coll. Use of antiviral drugs for seasonal influenza: Foundation document for practitioners - Update 2019. JAMMI. 2019;4:60-82. Rapports d’activité grippale au Canada (ÉpiGrippe)Gouvernement du Canada. Grippe (influenza): Surveillance ÉpiGrippe. 2020. Tableau comparatif des symptômes de l’influenza, de la COVID-19 et du rhumeAlberta Health Services. Disponible en ligne.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.12.248690v1?rss=1 Authors: Seitz, C., Casalino, L., Konecny, R., Huber, G., Amaro, R. E., McCammon, J. A. Abstract: Influenza neuraminidase is an important drug target. Glycans are present on neuraminidase, and are generally considered to inhibit antibody binding via their glycan shield. In this work we studied the effect of glycans on the binding kinetics of antiviral drugs to the influenza neuraminidase. We created all-atom in silico systems of influenza neuraminidase with experimentally-derived glycoprofiles consisting of four systems with different glycan conformations and one system without glycans. Using Brownian dynamics simulations, we observe a two- to eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. These glycans are capable of covering much of the surface area of neuraminidase, and the ligand binding inhibition is derived from glycans sterically occluding the primary binding site on a neighboring monomer. Our work also indicates that drugs preferentially bind to the primary binding site (i.e. the active site) over the secondary binding site, and we propose a binding mechanism illustrating this. These results help illuminate the complex interplay between glycans and ligand binding on the influenza membrane protein neuraminidase. Copy rights belong to original authors. Visit the link for more info

What are the new guidelines for influenza treatment? What are the diagnostic ratios of flu symptoms and tests? Time Stamps 03:10 The art of diagnosing the flu 05:17 Bayesian statistics and the diagnostic odds ratio 07:09 The ins and outs of diagnostic testing for the flu 08:44 Changes in influenza guidelines - testing and treatment 11:17 The not-so-rosy origin story of neuraminidase inhibitors (NAIs) 13:47 Neuraminidase inhibitors (NAIs), mortality benefit and limitations of studies 15:49Take aways

  Jeff: Welcome back to Emplify, the podcast corollary to EB Medicine’s Emergency Medicine Practice. I’m Jeff Nusbaum, and I’m back with my co-host, Nachi Gupta. This month, we’re talking about a topic that is ripe for review this time of year. We’re talking Influenza… Diagnosis and Management. Nachi: Very appropriate as the cold is settling in here in NYC and we’re already starting to see more cases of influenza. Remember that as you listen through the episode, the means we’re about to cover one of the CME questions for those of you listening at home with the print issue handy. Jeff: This month’s issue was authored by Dr. Al Giwa of the Icahn School of Medicine at Mount Sinai, Dr. Chinwe Ogedegbe of the Seton Hall School of Medicine, and Dr. Charles Murphy of Metrowest Medical Center. Nachi: And this issue was peer reviewed by Dr. Michael Abraham of the University of Maryland School of Medicine and by Dr. Dan Egan, Vice Chair of Education of the Department of Emergency Medicine at Columbia University. Jeff: The information contained in this article comes from articles found on pubmed, the cochrane database, center for disease control, and the world health organization. I’d say that’s a pretty reputable group of sources. Additionally, guidelines were reviewed from the american college of emergency physicians, infectious disease society of america, and the american academy of pediatrics. Nachi: Some brief history here to get us started -- did you know that in 1918/1919, during the influenza pandemic, about one third of the world’s population was infected with influenza? Jeff: That’s wild. How do they even know that? Nachi: Not sure, but also worth noting -- an estimated 50 million people died during that pandemic. Jeff: Clearly a deadly disease. Sadly, that wasn’t the last major outbreak… fifty years later the 1968 hong kong influenza pandemic, H3N2, took between 1 and 4 million lives. Nachi: And just last year we saw the 2017-2018 influenza epidemic with record-breaking ED visits. This was the deadliest season since 1976 with at least 80,000 deaths. Jeff: The reason for this is multifactorial. The combination of particularly mutagenic strains causing low vaccine effectiveness, along with decreased production of IV fluids and antiviral medication because of the hurricane, all played a role in last winter’s disastrous epidemic. Nachi: Overall we’re looking at a rise in influenza related deaths with over 30,000 deaths annually in the US attributed to influenza in recent years. The ED plays a key role in outbreaks, since containment relies on early and rapid identification and treatment. Jeff: In addition to the mortality you just cited, influenza also causes a tremendous strain on society. The CDC estimates that epidemics cost 10 billion dollars per year. They also estimate that an epidemic is responsible for 3 million hospitalized days and 31 million outpatient visits each year. Nachi: It is thought that up to 20% of the US population has been infected with influenza in the winter months, disproportionately hitting the young and elderly. Deaths from influenza have been increasing over the last 20 years, likely in part due to a growing elderly population. Jeff: And naturally, the deaths that we see from influenza also disproportionately affect the elderly, with up to 90% occurring in those 65 or older. Nachi: Though most of our listeners probably know the difference between an influenza epidemic and pandemic, let’s review it anyway. When the number of cases of influenza is higher than what would be expected in a region, an epidemic is declared. When the occurrence of disease is on a worldwide spectrum, the term pandemic is used. Jeff: I think that’s enough epidemiology for now. Let’s get started with the basics of the influenza virus. Influenza is spread primarily through direct person-to-person contact via expelled respiratory secretions. It is most active in the winter months, but can be seen year-round. Nachi: The influenza virus is a spherical RNA-based virus of the orthomyxoviridae family. The RNA core is associated with a nucleoprotein antigen. Variations of this antigen have led to the the 3 primary subgroups -- influenza A, B, and C, with influenza A being the most common. Jeff: Influenza B is less frequent, but is more frequently associated with epidemics. And Influenza C is the form least likely to infect humans -- it is also milder than both influenza A or B. Nachi: But back to Influenza A - it can be further classified based on its transmembrane or surface proteins, hemagglutinin and neuraminidase - or H and N for short. There are actually 16 different H subtypes and 9 different N subtypes, but only H1, H2, H3, and N1 and N2 have caused epidemic disease. Jeff: Two terms worth learning here are antigen drift and anitgen shift. Antigen drift refers to small point mutations to the viral genes that code for H and N. Antigen shift is a much more radical change, with reassortment of viral genes. When cells are infected by 2 or more strains, a new strain can emerge after genetic reassortment. Nachi: With antigen shift, some immunity may be maintained within a population infected by a similar subtype previously. With antigen drift, there is loss of immunity from prior infection. Jeff: The appearance of new strains of influenza typically involves an animal host, like pigs, horses, or birds. This is why you might be hear a strain called “swine flu”, “equine flu”, or “avian flu”. Close proximity with these animals facilitates co-infection and genetic reassortment. Nachi: I think that’s enough basic biology for now, let’s move on to pathophysiology. When inhaled, the influenza virus initially infects the epithelium of the upper respiratory tract and alveolar cells of the lower respiratory tract. Viral replication occurs within 4 to 6 hours. Incubation is 18 to 72 hours. Viral shedding is usually complete roughly 7 days after infection, but can be longer in children and immunocompromised patients. Jeff: As part of the infectious process and response, there can be significant changes to the respiratory tract with inflammation and epithelial cell necrosis. This can lead to viral pneumonia, and occasionally secondary bacterial pneumonia. Nachi: The secondary bacterial pathogens that are most common include Staph aureus, Strep pneumoniae, and H influenzae. Jeff: Despite anything you may read on the internet, vaccines work and luckily influenza happens to be a pathogen which we can vaccinate against. As such, there are 3 methods approved by the FDA for producing influenza vaccines -- egg-based, cell-based, or recombinant influenza vaccine. Once the season’s most likely strains have been determined, the virus is introduced into the medium and allowed to replicate. The antigen is then purified and used to make an injection or nasal spray. Nachi: It isn’t easy to create vaccines for all strains. H3N2, for example, is particularly virulent, volatile, and mutagenic, which leads to poor prophylaxis against this particular subgroup. Jeff: In fact, a meta-analysis on vaccine effectiveness from 2004-2015 found that the pooled effectiveness against influenza B was 54%, against the H1N1 pandemic in 2009 was 61%, and against the H3N2 virus was 33%. Not surprisingly, H3N2 dominant seasons are currently associated with the highest rates of influenza cases, hospitalizations, and death. Nachi: Those are overall some low percentages. So should we still be getting vaccinated? The answer is certainly a resounding YES.. Despite poor protection from certain strains, vaccine effectiveness is still around 50% and prevents severe morbidity and mortality in those patients. Jeff: That’s right. The 2017-2018 vaccine was only 40% effective, but this still translates to 40% less severe cases and a subsequent decrease in hospitalizations and death. Nachi: But before we get into actual hospitalization, treatment, and preventing death, let’s talk about the differential. We’re not just focusing on influenza here, but any influenza like illness, since they can be hard to distinguish. The CDC defines “influenza-like illness” as a temperature > 100 F, plus cough or sore throat, in the absence of a known cause other than influenza. Jeff: Therefore, influenza should really be considered on the differential of any patient who presents to the ED with a fever and URI symptoms. The differential when considering influenza might also include mycoplasma pneumoniae, strep pneumoniae, adenovirus, RSV, rhinovirus, parainfluenza virus, legionella, and community acquired MRSA. Nachi: With the differential in mind, let’s move on to prehospital care. For the prehospital setting, there isn’t much surprising here. Stabilize and manage the respiratory status with all of your standard tools - oxygen for those with mild hypoxia and advanced airway maneuvers for those with respiratory distess. Jeff: Of note, EMS providers should use face masks themselves and place them on patients as well. As community paramedicine and mobile integrated health becomes more common, this is one potential area where EMS can potentially keep patients at home or help them seek treatment in alternate destinations to avoid subjecting crowded ED’s to the highly contagious influenza virus. Nachi: It’s also worth noting, that most communities have strategic plans in the event of a major influenza outbreak. Local, state, and federal protocols have been designed for effective care delivery. Jeff: Alright, so now that the EMS crew, wearing proper PPE of course, has delivered the patient, who is also wearing a mask, to the ED, we can begin our ED H&P. Don’t forget that patients present with a range of symptoms that vary by age. A typical history is 2-5 days of fever, nasal congestion, sore throat, and myalgias. You might see tachycardia, cough, dyspnea, and chills too. Nachi: Van Wormer et al conducted a prospective analysis of subjective symptoms to determine correlation with lab confirmed influenza. They found the most common symptoms were cough in 92%, fatigue in 91%, and nasal congestion in 84%, whereas sneezing was actually a negative predictor for influenza. Jeff: Sneezing, really? Can’t wait to get the Press-Gany results from the sneezing patient I discharge without testing for influenza based on their aggressive sneezes! Nachi: Aggressive sneezes…? I can’t wait to see your scale for that. Jeff: Hopefully I’ll have it in next month’s annals. In all seriousness, I’m not doing away with flu swabs just yet. In another retrospective study, Monto et al found that the best multivariate predictors were cough and fever with a positive predictive value of 79%. Nachi: Yet another study in children found that the predominant symptoms were fever in 95%, cough in 77%, and rhinitis in 78%. This study also suggested that the range of fever was higher in children and that GI symptoms like vomiting and diarrhea were more common in children than adults. Jeff: Aside from symptomatology, there are quite a few diagnostic tests to consider including viral culture, immunofluoresence, rt-pcr, and rapid antigen testing. The reliability of testing varies greatly depending on the type of test, quality of the sample, and the lab. During a true epidemic, formal testing might not be indicated as the decision to treat is based on treatment criteria like age, comorbidities, and severity of illness. Nachi: We’ll get to treatment in a few minutes, but diving a bit deeper into testing - there are 3 major categories of tests. The first detects influenza A only. The second detects either A or B, but cannot distinguish between them; and the third detects both influenza A and B and is subtype specific. The majority of rapid testing kits will distinguish between influenza A and B, but not all can distinguish between them. Fluorescent antibody testing by DFA is relatively rapid and yields results within 2 to 4 hours. Jeff: Viral culture and RT-PCR remain the gold standard, but both require more time and money, as well as a specialized lab. As a result, rapid testing modalities are recommended. Multiple studies have shown significant benefit to the usefulness of positive results on rapid testing. It’s safe to say that at a minimum, rapid testing helps decrease delays in treatment and management. Nachi: Looking a bit further into the testing characteristics, don’t forget that the positive predictive value of testing is affected by the prevalence of influenza. In periods of low influenza activity (as in the summer), a rapid test will have low PPV and high NPV. The test is more likely to yield false positive results -- up to 50% according to one study when prevalence is below 5%. Jeff: And conversely, in periods of high influenza activity, a rapid test will have higher PPV and lower NPV, and it is more likely to produce a false negative result. Nachi: In one prospective study of patients who presented with influenza-like illness during peak season, rapid testing was found to be no better than clinical judgement. During these times, it’s probably better to reserve testing for extremely ill patients in whom diagnostic closure is particularly important. And since the quality of the specimen remains important, empiric treatment of critically ill patients should still be considered. Jeff: Which is a perfect segway into our next topic - treatment, which is certainly the most interesting section of this article. To start off -- for mild to moderate disease and no underlying high risk conditions, supportive therapy is usually sufficient. Nachi: Antiviral therapy is reserved for those with a predicted severe disease course or with high risk conditions like long-standing pulmonary disease, pregnancy, immunocompromise, or even just being elderly. Jeff: Note to self, avoid being elderly. Nachi: Good luck with that. Anyway, early treatment with antivirals has been shown to reduce influenza-related complications in both children and adults. Jeff: Once you’ve decided to treat the patient, there are two primary classes of antivirals -- adamantane derivatives and neuraminidase inhibitors. Oh and then there is a new single dose oral antiviral that was just approved by the FDA… baloxavir marboxil (or xofluza), which is in a class of its own -- a polymerase endonuclease inhibitor. Nachi: The oldest class, the adamantane derivatives, includes amantadine and rimantadine. Then the newer class of neuraminidase inhibitors includes oseltamavir (which is taken by mouth), zanamavir (which is inhaled), and peramivir (which is administered by IV). Jeff: Oseltamavir is currently approved for patients of all ages. A 2015 meta analysis showed that the intention-to-treat infected population had a shorter time to alleviation of all symptoms from 123 hours to 98 hours. That’s over a day less of symptoms, not bad! There were also fewer lower respiratory tract complications requiring antibiotics and fewer admissions for any cause. Really, not bad! Nachi: Zanamavir is approved for patients 7 and older -- or for children 5 or older for disease prevention. Zanamavir has been associated with possible bronchospasm and is contraindicated in patients with reactive airway disease. Jeff: Peramivir, the newest drug in this class, is given as a single IV dose for patients with uncomplicated influenza who have been sick for 2 days or less. Peramavir is approved for patients 2 or older. This is a particularly great choice for a vomiting patient. Nachi: And as you mentioned before, just last month, the FDA approved baloxavir, a single dose antiviral. It’s effective for influenza type A or B. Note that safety and efficacy have not been established for patients less than 12 years old, weighing less than 40 kg, or pregnant or lactating patients. Jeff: Unfortunately, there has been some pretty notable antiviral resistance in the recent past, moreso with the adamantane class, but recently also with the neuraminidase inhibitors. In 2007-2008, an oseltamivir-resistant H1N1 strain emerged globally. Luckily, cross-resistance between baloxavir and the adamantanes or neuraminidase inhibitors isn’t expected, as they target different viral proteins, so this may be an answer this year, and in the future. Nachi: Let’s talk chemoprophylaxis for influenza.. Chemoprophylaxis with oseltamavir or zanamavir can be considered for patients who are at high risk for complications and were exposed to influenza in the first 2 weeks following vaccination, patients who are at high risk for complications and cannot receive the vaccination, and those who are immunocompromised. Jeff: Chemoprophylaxis is also recommended for pregnant women. For postexposure prophylaxis for pregnant women, the current recommendation is to administer oseltamivir. Nachi: We should also discuss the efficacy of treatment with antivirals. This has been a hotly debated topic, especially with regards to cost versus benefit… In a meta-analysis, using time to alleviation of symptoms as the primary endpoint, oseltamavir resulted in an efficacy of 73% (with a wide 95% CI from 33% to 89%). And this was with dose of 150mg/day in a symptomatic influenza patient. Jeff: Similarly zanamavir given at 10mg/day was 62% effective, but again with a wide 95% CI from 15% to 83%. And, of note, other studies have looked into peramivir, but have found no significant benefits other than the route of delivery. Nachi: In another 2014 study by Muthuri et al., neuraminidase inhibitors were associated with a reduction in mortality -- adjusted OR = 0.81 (with a 95% CI 0.70 to 0.93). Also when comparing late treatment with early treatment (that is, within 2 days of symptom onset), there was a reduction in mortality risk with adjusted OR 0.48 (95%CI 0.41-0.56). These associations with reduction in mortality risk were less pronounced and less significant in children. Jeff: Mortality benefit, not bad! They further found an increase in mortality hazard ratio with each day’s delay in initiation of treatment up to 5 days, when compared to treatment initiated within 2 days. Nachi: But back to the children for a second -- another review of neuraminidase inhibitors in children < 12 years old found duration of clinical symptoms was reduced by 36 hours among previously healthy children taking oseltamivir and 30 hours by children taking zanamivir. Jeff: I think that’s worth summarizing - According to this month’s author’s review of the best current evidence, use of neuraminidase inhibitors is recommended, especially if started within 2 days, for elderly patients and those with comorbidities. Nachi: Seems like there is decent data to support that conclusion. But let’s not forget that these medications all have side effects. Jeff: These drugs actually tend to be well tolerated.The most frequently noted side effect of oseltamavir is nausea and vomiting, while zanamavir is associated with diarrhea. Nachi: Amazing. Let’s talk disposition for your influenza patient. Jeff: Disposition will depend on many clinical factors, like age, respiratory status, oxygen saturation, comorbid conditions, and reliability of follow up care. Admission might be needed not only to manage the viral infection, but also expected complications. Nachi: If you’re discharging a patient, be sure to engage in shared decision making regarding risks and benefits of available treatments. Ensure outpatient follow up and discuss return to er precautions. Jeff: Also, the CDC recommends that these patients stay home for at least 24 hours after their fever has broken. Nachi: With that -- Let’s summarize the key points and clinical pearls from this month’s issue J: Even though influenza vaccine effectiveness is typically only 50%, this still translates to a decrease in influenza-related morbidity and mortality. 2. The CDC defines influenza-like illness as a temperature > 100 F with either cough or sore throat, in the absence of a known cause other than influenza. 3. When influenza is suspected in the prehospital setting, patients and providers should wear face masks to avoid spreading the virus. 4. In the emergency department, standard isolation and droplet precautions should be maintained for suspected or confirmed infections. 5. The most common symptoms of influenza in adults are cough, fatigue, nasal congestion, and fever. Sneezing is a negative predictor in adults. 6. In children, the most common presenting symptoms are fever, cough, and rhinitis. Vomiting and diarrhea is also more common in children than adults. 7. Rapid testing and identification results in decreased delays in treatment and management decisions. 8. During peak flu season, clinical judgement may be as good as rapid testing, making rapid testing less necessary. J: Rapid testing may be more beneficial in times of lower disease prevalence. 10. Empiric treatment of critically ill patients should be considered even if rapid testing is negative. J: For mild to moderate disease and no underlying high-risk conditions, supportive therapy is usually sufficient. 12.For more ill patients or those at substantial risk for complications, consider antiviral treatment. 13.Oseltamivir is approved for patients of all ages, and reduces the length of symptoms by one day. 14.When treating influenza, peramivir is an ideal agent for the vomiting patient. 15.Baloxavir is a new single-dose antiviral agent approved by the FDA in October 2018. It works in a novel way and is effective for treatment of influenza A and B. 16.Chemoprophylaxis with oseltamivir or zanamivir should be considered in patients who are immunocompromised or patients who are at elevated risk for complications and cannot receive the vaccination. 17.Consider oseltamivir as post exposure prophylaxis in pregnant women. 18.Neuraminidase inhibitors are associated with decreased duration of symptoms and complications, especially if started within 2 days of symptom onset. J: So that wraps up episode 23 - Influenza: Diagnosis and Management in the Emergency Department. N: Additional materials are available on our website for Emergency Medicine Practice subscribers. For our subscribers: be sure to go online to get your CME credit for this issue, which includes 3 pharmacology CME credits. J: Also, for our NP and PA listeners, we have a special offer this month: You can get a full year of access to Emergency Medicine Practice for just $199--including lots of pharmacology, stroke, and trauma CME--and so much more! To get this special deal, go to www.ebmedicine.net/APP. Again, that’s www.ebmedicine.net/APP. N: If you’re not a subscriber, consider joining today. You can find out more at www.ebmedicine.net/subscribe. Subscribers get in-depth articles on hundreds of emergency medicine topics, concise summaries of the articles, calculators and risk scores, and CME credits. You’ll also get enhanced access to the podcast, including the images and tables mentioned. You can find everything you need to know at ebmedicine.net/subscribe. J: And the address for this month’s credit is ebmedicine.net/E1218. As always, the you heard throughout the episode corresponds to the answers to the CME questions. Lastly, be sure to find us on iTunes and rate us or leave comments there. You can also email us directly at emplify@ebmedicine.net with any comments or suggestions. Talk to you next month!    

Host: Vincent Racaniello Guest: Peter Palese Vincent speaks with Peter Palese about his illustrious career in virology, from early work on neuraminidases to universal influenza virus vaccines.   Become a patron of TWiV! Links for this episode Palese Laboratory Pig kidney neuraminidase (Hoppe Seylers Z Physiol Chem) DNAse in cytoplasmic DNA virus (Virology) Inhibitor of influenza virus neuraminidase (Virology) Influenza neuraminidase defective mutants (Virology) Swine influenza virus of 1976 RNA pattern (Nature) 1977 influenza H1N1 similar to 1950s strains (Nature) H5N1 influenza: Facts, not fear (PNAS) Influenza HA stalk immunity in ferrets (J Virol) This episode is sponsored by CuriosityStream. Get two months free when you sign up at curiositystream.com/microbe and use the promo code MICROBE. Send your virology questions and comments to twiv@microbe.tv

Hochpathogene Aviäre Influenzaviren (HPAIV) des Subtypes H5N1 zirkulieren seit den ersten Ausbrüchen vor mehr als 10 Jahren in Wirtschaftsgeflügel und Wildvögeln, vor allem in Asien und Afrika. Vakzinekampagnien mit ungeeigneten oder unwirksamen Impfstoffen sowie Transporte von infiziertem Geflügel, sowie Wildvogelzüge führten nicht nur zur Verbreitung der Viren, sondern auch zu Reassortierungen mit anderen zirkulierenden Influenzaviren und zur antigenetischen Drift. Bis heute ist kein Impfstoff verfügbar der ausreichenden und schnellen Schutz vor einer HPAIV H5N1 Infektion, sowie der Ausscheidung bietet, genauso wie eine einfache Applikation ermöglicht und sowohl im Säugetier, als auch Vogel einsetzbar ist. Im Falle eines Ausbruches wäre eine solche Vaccine das perfekte Werkzeug, um eine Pandemie zu verhindern. Die in dieser Dissertation vorgestellten Arbeiten zeigen die in-vitro und in-vivo Charakterisierung und einer Neuraminidase-negativen H5N1 Mutante, so wie den Einsatz als Impfstoffmodel zur Untersuchung der Frühimmunisierung. Ein hochpathogenes H5N1 Isolat des Stammes 2.1 (A/swan/Germany/R65/2006) wurde fünfzigmal im embryonierten Hühnerei passagiert. Den Passagen wurde bei jedem Durchgang polybasisches Hühnerserum mit Antikörper gegen H5 und N2 beigemischt, um einen selektiven Druck auf das Virus zu erzeugen. Die daraus resultierende Mutante zeigte überaschenderweise nicht die erwarteten Veränderungen und Anpassungen im Haemagglutinin, sondern Deletionen und „Segment-shuffling“ im Segment 6, welches für das Neuraminidaseprotein kodiert. Des Weiteren konnte keine Neuraminidaseaktivität mehr nachgewiesen werden. Die Deletionen führten zu Veränderungen im Wachstumsverhalten des Virus und der Pathogenität im Tier. So konnte hier gezeigt werden, dass die Mutante ohne Zugabe von externer Neuraminidase oder Adaptation des Haemagglutinins in Zellkultur und Ei hohe Infektionstiter erreichen kann. Im Vergleich zum Ursprungsvirus aber Wachstumsdefizite aufweist, die sich in kleineren Plaques und langsamerem Wachstum auf Zellkultur zeigen. Infektionsversuche im Huhn zeigten, dass das Virus weder Klinik auslöst, noch ausgeschieden oder übertragen wird, aber eine gute Immunantwort induziert. Hohe Antikörper konnten nur erreicht werden, wenn Hühner intramuskulär infiziert wurden, wohingegen eine Applikation über den oronasalen Weg nicht bei allen Tieren gelang. Die gute Immunantwort und Apathogenität des Virus machten es im weiteren Verlauf zu einem geeigneten Kandidaten für Frühimmunisierungsversuche im Säugetier- und Vogelmodell. So wurden Balb/C Mäuse, Frettchen und Hühner ein, drei und sieben Tage vor einer H5N1 Belastungsinfektion mit der H5N1 Mutante intramuskulär oder intranasal immunisiert. Dabei konnte ein 100% Schutz vor klinischen Symptomen und der Ausscheidung des Challenge-Virus nach nur 7 Tagen gezeigt werden. Darüber hinaus waren die Tiere vor Klinik bereits drei Tage nach der Immunisierung geschützt, wobei aber virale RNA in oronasalen Proben und auch den Organen nachgewiesen werden konnte. Die Neuraminidasedeletion der Mutante ermöglichte außerdem eine Unterscheidung von immunisierten zu infizierten Tieren, da erstere im ELISA NP- aber keine NA-Antikörper zeigten, wohingegen infizierte Tiere Antikörper gegen beide Proteine bildeten. In Zukunft könnten NA negative Influenzaviren zusätzlich oder als Alternative zu den gängigen stamping out Strategien eingesetzt werden. Dafür aber sind weiter Untersuchungen essentiell. Die hochpathogene Spaltstelle im HA von „EscEgg50A“ impliziert das Risiko mit zirkulierenden AI Stämmen zu reassortieren und ist daher für den Einsatz zum Beispiel in Zuchtherden ungeeignet. Darüber hinaus ist das Wissen über das NA Protein und seine Funktionsweise sehr lückenhaft und NA-negative Mutanten könnten für zukünftige Untersuchungen genutzt werden.

Hosts: Vincent Racaniello, Alan Dove, and Kathy Spindler Vincent, Alan and Kathy review novel approaches to preventing influenza virus infection. Links for this episode: Ultraprotective influenza vaccine in mice (PNAS) Vectored immunoprophylaxis of influenza in mice (Nat Biotech) Intranasal antibody gene transfer protects agains influenza (Sci Transl Med) Estimating influenza associated deaths (CDC) Multistate HAV outbreak (CDC) Subscribe to Microbeworld video (YouTube) Save podcasting (EFF) Letters read on TWiV 236 Weekly Science Picks Alan - Psychology of antivaccinationistsVincent -  Virology on CourseraKathy - Meteorites through the ages Listener Pick of the Week Basel - Self-medication in animalsSheryl - Noadi's artFelicity - Survival of the Sickest by Sharon Moalem Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Hosts: Vincent Racaniello, Alan Dove, and Kathy Spindler Vincent, Alan, and Kathy discuss new influenza virus NA inhibitors, detection of EEEV antibody and RNA in snakes, and replication of the coronavirus EMC in human airway epithelial cells. Links for this episode: International Women's Day 2013 Condit Dam, 6 weeks later (Vimeo) Influenza HA assay Covalent influenza NA inhibitors (ScienceExpress) Defective influenza HA mutants (Virology) New flu drug (BBC, e! Science) EEEV antibody, RNA in snakes (Am J Trop Med Hyg) EEEV (CDC) Zoonotic potential of CoV-EMC (mBio) CoV-EMC update (ProMedMail, CDC) CoV-EMC travel update (CDC) Letters read on TWiV 223 Weekly Science Picks Kathy - Finkbeiner test and Women in ScienceAlan - New flu vaccine efficacy study (CDC)Vincent -  Threading the NEIDL video Listener Pick of the Week Steve - Prof. Joan Steitz on viral RNAEd - Archiving history of molecular biology: Press release, video, CSHL archives and videos Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv