ETIDIOH - NEW

Key Points -- Question:   In adults with influenza requiring admission to hospital, is oseltamivir treatment within the first 2 days of admission, when compared with supportive care without oseltamivir, associated with a decreased risk of death in hospital? -- Findings:  In this cohort study of 11 073 patients hospitalized with influenza, oseltamivir treatment was associated with an adjusted risk reduction of 1.8% for in-hospital mortality when compared with supportive care. -- Meaning:  The findings of this study support current guidelines that recommend oseltamivir treatment for patients admitted to hospital with influenza; clinical trials should be conducted to generate better quality evidence. Abstract Importance    Current guidelines recommend oseltamivir treatment for all patients hospitalized with influenza, but this guidance is based on suboptimal evidence. Objective    To evaluate outcomes associated with oseltamivir treatment when compared wi...

Abstract Avian influenza viruses (AIVs) pose a growing global health threat , particularly in low- and middle-income countries (LMICs), where limited surveillance capacity and under-resourced healthcare systems hinder timely detection and response. Migratory birds play a significant role in the transboundary spread of AIVs, yet data from key regions along migratory flyways remain sparse. To address these surveillance gaps, we conducted a study between December 2021 and February 2023 using fresh bird guano collected across 10 countries in the Global South . Here, we show that remote, uninhabited regions in previously unsampled areas harbor a high diversity of AIV strains , with H5N1 emerging as the most prevalent . Some of these H5N1 samples also carry mutations that may make them less responsive to the antiviral drug oseltamivir . Our findings documented the presence of AIVs in several underrepresented regions and highlighted critical transmission hotspots where viral evolution may be ...

ABSTRACT Background and Objectives This randomised controlled trial evaluated whether higher doses of oseltamivir would improve virological and clinical outcomes in severe influenza patients requiring invasive mechanical ventilation. Methods Forty intubated adult patients with severe influenza A or B from four intensive care units in Hong Kong were enrolled and randomised to receive either a double dose (300 mg/day) or a triple dose (450 mg/day) of oseltamivir for 10 days. Baseline data were collected, and outcomes were assessed daily using SOFA and Murray scores. Viral RNA was quantified from nasopharyngeal and tracheal aspirates. The primary outcome was the viral clearance rate after 5 days of treatment; secondary outcomes included 28-day and hospital mortality rates, changes in viral load, and serial SOFA and Murray scores. Results Viral clearance rates after 5 days of treatment were low and similar between the double (3/20, 15%) and triple-dose groups (2/20, 10%). No significant di...

Abstract Background Every year, more than one billion people around the world are infected with influenza , an acute infection of the respiratory tract. Influenza spreads from person to person through air, contaminated hands or objects. Antiviral and immunomodulatory drugs are available for treatment of patients and prophylaxis of exposed persons. Reverse transcription polymerase chain reaction (RT-PCR), nucleic acid amplification tests (NAATs) and rapid tests are available for the diagnosis of influenza.  Objective   The aim of this World Health Organization (WHO) guideline is to provide recommendations for the diagnosis, drug treatment and prophylaxis of influenza. Method This updated guideline has been developed in accordance with standards for trustworthy guidelines. The recommendations are based on systematic reviews on safety and effectiveness. They take into account the magnitude of benefits and harms of treatments, the reliability of the evidence, and the needs of pati...

Highlights •  Reconstituted human airway epithelia (HAE) are more effective than cell lines or mouse models for generating and predicting resistance-conferring mutations. •  The resistance barrier of oseltamivir is superior to baloxavir or HA targeting compounds in HAE or mouse model. •  HA-targeting therapeutics quickly led to resistant HA mutations without compromising viral fitness. •  A baloxavir-resistant virus with PA mutations E23G and C241Y was isolated in HAE. •  Combined therapy using clinical antiviral compounsd and HA-targeting compounds did not prevent the emergence of HA mutations. Abstract Influenza viruses pose a significant threat due to annual epidemics and pandemic potential . Resistance to current antivirals underscores the need for new drugs and strategies to prevent its emergence. We previously developed two novel HA-targeting compounds (CD-6’SLN and CD-SA) with demonstrated efficacy against influenza A and B strains . Here, we compared the...

Abstract Influenza remains a global public health concern, and although the antiviral drug oseltamivir is widely used to treat infections , questions regarding its actual antiviral efficacy and clinical benefits remain. Here, we evaluated the effects of oseltamivir on viral shedding dynamics in the context of experimental influenza infection . We analyzed individual participant data, including viral load, time to symptom alleviation, and laboratory test measurements, obtained from three publicly available clinical trials involving experimental infections with influenza A and B viruses. We applied mathematical modeling and estimated parameters using a nonlinear mixed-effects model to capture viral infection dynamics. Our analysis revealed that, compared with placebo groups, the oseltamivir-treated groups tended to have lower values in terms of viral load area under the curve , duration of infection, peak viral titer, and time to peak; however, most of these differences were not signific...

Abstract Objective :  To analyze the epidemiological, etiological and genetic characteristics of influenza virus in Shandong Province during 2023-2024.  Methods :  The surveillance data of influenza-like illness (ILI) in sentinel hospitals in Shandong from 2023 to 2024 were collected and analyzed. The isolated influenza strains with hemagglutination titers ≥8 were selected for antigenicity analysis , drug susceptibility test, gene sequencing and evolutionary analysis .  Results :  From 2023 to 2024, the positive rate of influenza virus in Shandong was 8.51% (23 663/277 995), the highest positive rate was in the age group of 5-14 years (15.78%, 6 073/38 478), and the highest positive rate was in the 49th week (35.86%, 2 264/6 313). Both antigenicity analysis and evolutionary analysis showed that the A(H1N1)pdm09 subtype and B(Victoria) strain had good matching effect and close evolutionary distance with the 2023-2024 surveillance year vaccine strain. The A(H3N2) ...

Abstract Testing approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species, including dairy cows , is critical to public health and pre-pandemic planning . It cannot be tested in humans due to A(H5N1) disease severity. Here, in mice, we demonstrate that US FDA-approved baloxavir treatment mediates improved disease outcomes ( survival and viral dissemination ) over oseltamivir after lethal intranasal and ocular challenge with A(H5N1)-contaminated cow milk. Source: Nature Microbiology,  https://www.nature.com/articles/s41564-025-01961-5 ____

Abstract During 2023-2024, highly pathogenic avian influenza A(H5N1) viruses from clade 2.3.2.1c caused human infections in Cambodia and from clade 2.3.4.4b caused human infections in the Americas . We assessed the susceptibility of those viruses to approved and investigational antiviral drugs . Except for 2 viruses isolated from Cambodia , all viruses were susceptible to M2 ion channel-blockers in cell culture-based assays. In the neuraminidase inhibition assay , all viruses displayed susceptibility to neuraminidase inhibitor antiviral drugs oseltamivir, zanamivir, peramivir, laninamivir , and AV5080. Oseltamivir was ≈4-fold less potent at inhibiting the neuraminidase activity of clade 2.3.4.4b than clade 2.3.2.1c viruses. All viruses were susceptible to polymerase inhibitors baloxavir and tivoxavir and to polymerase basic 2 inhibitor pimodivir with 50% effective concentrations in low nanomolar ranges. Because drug-resistant viruses can emerge spontaneously or by reassortment, close m...

Abstract Background Influenza is a pervasive respiratory infection which disproportionately burdens long-term care residents. To limit outbreaks, guidelines recommend antiviral prophylaxis, particularly oseltamivir or zanamivir , despite acknowledging the inadequate supporting evidence . Therefore, we aimed to review the literature on the efficacy of oseltamivir, zanamivir, and baloxavir prophylaxis for influenza in long-term care. Methods Medline, Embase, PubMed, and several other databases were searched from inception to August 16, 2023. For inclusion, observational studies or randomized controlled trials (RCTs) had to report influenza-like illness (ILI) or infection rates amongst adult long-term care populations receiving prophylaxis. Outcome values were meta-analyzed as intervention-specific pooled proportions (PPs) and risk ratios (RRs) when applicable. Risk of bias was assessed via the Cochrane risk of bias tool 2.0 and Joanna Briggs Institute checklist. Results In total, 14 stud...

Abstract It is essential to understand the molecular mechanisms of influenza antiviral therapeutics to evaluate their efficacy. Virus plaque assays are commonly used to assess the antiviral effects of drugs on virus replication ; however, this method is labor-intensive and can present challenges. We avoided this method by using a replication-competent influenza A virus (IAV) expressing a reporter fluorescent gene fused to the non-structural protein 1 (NS1) gene. The reporter IAV was detectable in normal human bronchoepithelial (NHBE) infected cells and offered an improved method to determine the therapeutic efficacy of the antiviral drugs probenecid and oseltamivir compared to a standard plaque assay. This method provides an excellent means for evaluating therapeutic approaches against IAV. Source: Viruses,  https://www.mdpi.com/1999-4915/17/3/335 ____

Abstract We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada . Isolates from 8 farms reveal a mutation in the neuraminidase protein (H275Y) that is exceptionally rare among clade 2.3.4.4b viruses (present in 0.045% of publicly available clade 2.3.4.4b isolates). NA-H275Y is a well-known marker of resistance to the neuraminidase inhibitor oseltamivir . We demonstrate that this substitution maintains its resistance phenotype on the genetic background of H5N1 clade 2.3.4.4b viruses. Source: Emerging Microbes and Infections,  https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2469643 ____

Natalia A. Ilyushina {a b}, Nicolai V. Bovin {c}, Robert G. Webster {a d}, Elena A. Govorkova  {a b} a} Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA; b} The D.I. Ivanovsky Institute of Virology, Gamaleya 16, Moscow 123098, Russia; c} Shemyakin Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia; d} Department of Pathology, University of Tennessee, Memphis, TN 38105, USA Received 21 November 2005, Accepted 26 January 2006, Available online 21 February 2006. Abstract Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers . On the other hand, the emergence of variants with low susceptibility to the neuraminidase (NA) inhibitors is limited. In the present study we examined whether combination therapy with two classes of anti-influenza drugs can affect the emergence of resistant variants in vitro. We observed that viru...

To the Editor : Highly pathogenic avian influenza A(H5N1) viruses are circulating among wild birds and poultry in British Columbia, Canada .1 These viruses are also recognized to cause illness in humans . Here, we report a case of critical illness caused by influenza A(H5N1) virus infection in British Columbia. On November 4, 2024, a 13-year-old girl with a history of mild asthma and an elevated body-mass index (the weight in kilograms divided by the square of the height in meters) of greater than 35 presented to an emergency department in British Columbia with a 2-day history of conjunctivitis in both eyes and a 1-day history of fever . She was discharged home without treatment, but cough, vomiting, and diarrhea then developed, and she returned to the emergency department on November 7 in respiratory distress with hemodynamic instability. On November 8, she was transferred, while receiving bilevel positive airway pressure, to the pediatric intensive care unit at British Columbia Child...

{Summary as of December 26 '24} What to know -- This guidance outlines CDC’s recommendations for preventing human exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses and infection prevention and control measures, including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons , and antiviral chemoprophylaxis of exposed persons. Summary The purpose of this guidance is to outline CDC's recommendations for preventing exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses, infection prevention and control measures including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons (including persons exposed to sick or dead wild and domesticated animals and livestock with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus), and antiviral chemoprophylaxis of exposed person...

Summary The purpose of this guidance is to outline CDC's recommendations for preventing exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses, infection prevention and control measures including the use of personal protective equipment , testing, antiviral treatment , patient investigations , monitoring of exposed persons (including persons exposed to sick or dead wild and domesticated animals and livestock with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus), and antiviral chemoprophylaxis of exposed persons. These recommendations are based on available information and will be updated as needed when new information becomes available. (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html _____