ETIDIOH - NEW

  Abstract As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received 12,180 human influenza-positive samples during 2024 . Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties . Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. During 2024 , influenza A( H1N1 )pdm09 and A( H3N2 ) viruses predominated , accounting for 33% and 42%, respectively, of all viruses received, compared to 5% for influenza B/Victoria . Of note, one influenza A(H5N1) virus was also received in 2024 . The majority of A(H1N1)pdm09 (98%), A(H3N2) (88%) and influenza B (100%) viruses analysed at the Centre were found to be antigenically and genetically similar to the respective WHO recommended vaccine strains for the Southern Hemisphere in 2024...

  Abstract Intercontinental spread of highly pathogenic avian influenza A(H5N1) viruses poses significant pandemic risks and necessitates strong protective countermeasures . We evaluated the therapeutic efficacy of the neuraminidase inhibitor oseltamivir , the polymerase inhibitors baloxavir and favipiravir , and an ion-channel blocker amantadine , against severe influenza A( H5N1 ) virus infection in female BALB/c mice . Baloxavir (≥10 mg/kg, 1 dose) fully protected mice from death , significantly reduced virus respiratory replication, and prevented neuroinvasion . Oseltamivir (≥100 mg/kg/day for 5 days) provided limited survival benefits , reduced lung titers but failed to prevent viral neuroinvasion . Favipiravir (≥100 mg/kg/day for 5 days) provided partial protection , although did not reduce viral titers in lungs and brain . Amantadine provided no benefits . Although all drugs inhibited A(H5N1) viruses in vitro, in vivo correlations did not extend beyond baloxavir . Our result...

  Abstract Objective The H7N9 avian influenza virus, identified in China in 2013, has posed a significant threat to public health due to its high mortality rate . This systematic review aims to evaluate the clinical characteristics and mortality risk factors of H7N9 patients. Methods English and Chinese databases (PubMed, Web of Science, Embase, CNKI, VIP, Wanfang) were searched for studies on laboratory-confirmed H7N9 cases with available data on symptom onset, diagnosis time, clinical features, oseltamivir administration, and outcomes . Univariate and multivariate analyses were performed on the pooled case data to assess the relationship between clinical factors and mortality risk. Results A total of 166 studies including 237 H7N9 cases were analyzed , with an overall mortality rate of 41.77%. Univariate analysis showed higher mortality in patients with advanced age ≥ 66 years (62.50%), those with underlying diseases (60.20%), those who received oseltamivir ≥ 8 days after symptom...

  Abstract Introduction Seasonal influenza causes significant global morbidity, mortality, and economic burden . Ongoing viral evolution can lead to vaccine mismatch and the emergence of antiviral resistance , highlighting the importance of genomic surveillance. The 2024–2025 influenza season was characterized by high incidence and increased hospitalizations. Methods We analyzed influenza A virus (IAV) genomes and clinical characteristics from the 2024–2025 season . Whole-genome sequencing was performed on 648 influenza A–positive clinical specimens collected between October 2024 and April 2025. Results Hemagglutinin (HA) sequences were recovered from 74.23% (481/648) of samples and used for subtyping and phylogenetic analysis. A(H1N1)pdm09 and A(H3N2) viruses co-circulated , representing 55.5% and 44.5% of cases, respectively. Among A(H1N1)pdm09 viruses, the HA1 substitution T120A , located near the Sa antigenic site , increased more than twofold compared with the prior season. Ci...

  Abstract Neuraminidase inhibitors (NAIs) and cap-dependent endonuclease inhibitors (CENIs) represent two classes of antiviral drugs recommended for early treatment of patients with seasonal influenza A virus (IAV) infections. However, only limited human data , particularly on combination antiviral treatment , are available to inform optimal dosing regimens against novel IAVs, including highly pathogenic avian influenza A(H5N1) virus , associated with severe disease . Clade 2.3.4.4b A( H5N1 ) viruses have caused outbreaks in avian and mammalian species worldwide , highlighting the need to assess antiviral drug efficacy against these strains. We challenged ferrets with a D1.1 genotype A(H5N1) virus and treated infected animals with the NAI oseltamivir phosphate (OST) and the CENI baloxavir acid (BXA), alone or in combination , with treatment onset commencing pre- or post-symptom onset (24- or 48-hours post-inoculation (p.i.), respectively). When administered pre- or post-illness on...

  Highlights •  Nonspecific early signs hinder prompt diagnosis of H10N3 infection. •  H10N3 human infection remains rare but with high clinical severity. •  All patients had bird exposure and developed fever, cough, and dyspnoea. •  Diagnosis was confirmed by sequencing; imaging revealed viral pneumonia. Abstract Background Since the first human case of H10N3 Avian Influenza in Jiangsu, China (April 2021), three cases have been reported globally. However, clinical and treatment data remain limited. Therefore, we describe the fourth patient’s epidemiology, clinical manifestations, diagnostics, treatment. Case presentation A 23-year-old woman, previously well , presented on 12 Dec 2024 with fever, dry cough and breathlessness after pig and chicken contact . CT showed bilateral pneumonia . Despite high-flow oxygen and broad-spectrum antibiotics she deteriorated , requiring intubation, lung-protective ventilation and VV-ECMO . Bronchoalveolar lavage isolated H10N3 ...

  Context and significance The avian influenza A virus subtype H10N3 is a possible candidate for causing a fatal flu and may present a serious public health threat . Research increasingly shows that the avian influenza virus H10N3 can be transmitted from birds to humans , causing severe viral pneumonia and potentially leading to acute respiratory distress syndrome and respiratory failure . Researchers at the Fourth People’s Hospital of Nanning (China) provide evidence supporting the cross-species transmission of the avian influenza virus H10N3 to humans, which can give rise to severe pneumonia. The authors report that a female patient with avian influenza virus H10N3 infection, who was suffering from severe pneumonia , respiratory failure, pneumothorax , and numbness and dysesthesia in her feet , recovered after receiving appropriate therapy and was discharged from the hospital. Highlights •  A young woman contracted the avian influenza virus H10N3 •  Secondary infections...

Abstract Influenza A virus (IAV) poses a significant global health risk, with highly pathogenic strains like H5N1 (CFR ~52%) causing severe disease compared to less lethal but more transmissible strains like H1N1 (CFR 0.01-0.03%). Although IAV primarily infects lung epithelial cells , causing cell death and tissue damage , the molecular basis of strain-specific pathogenesis remains poorly understood. Here we show that in cell culture , H5N1 induced more rapid and extensive cell death than H1N1. Since Interferon (IFN) signaling is key to innate immunity, we examined its role in virus-induced cell death using STAT1-knockout A549 cells and JAK/STAT pathway inhibitors like Baricitinib . Both approaches reduced cell death across various IAV strains, including H1N1, H5N1, H7N9 , and H3N2 . However, inhibition increased viral titers , raising concerns about its clinical use in isolation. To overcome this, we tested a combination of Oseltamivir (antiviral) and Baricitinib (anti-inflammatory). ...

Highlights •  Mol shows greater antiviral effects against IAV and IBV in cell cultures. •  Mol and Ose together showed a synergistic effect against IAV. •  In mice, Mol alone or with Ose reduced lung injury and viral load. Abstract Oseltamivir, a neuraminidase inhibitor, is widely used in the clinic for treating influenza virus infections . However, suboptimal efficacy and risk of drug resistance development remain major challenges. Molnupiravir , a ribonucleoside analog, was originally developed to treat influenza, but was repurposed and first approved for treating COVID-19 in 2021. Considering their complementary mode-of-actions, this study aimed to investigate the combinatorial activities of oseltamivir and molnupiravir against influenza virus infections . In cell culture models, we found that β-d-N4-hydroxycytidine (NHC), the active form of molnupiravir, exerted more potent antiviral activities against influenza A and B viruses , when compared to oseltamivir treatment...

{Excerpt} Highly pathogenic avian influenza (HPAI) A(H5Nx) clade 2.3.4.4b viruses have been circulating in North America since late 2021. Since their initial incursion, they have been associated with unprecedented mortality in wild birds, domestic poultry, and marine mammals throughout the Americas, and are now seen across all global regions except Oceania. Furthermore, transmission among dairy cattle and poultry in the United States has led to growing numbers of human cases, and there was a severe human case in Canada with no known infected animal exposure (1,2). (...) Source: Journal of the Association of Medical Microbiology and Infectious Disease Canada,  https://utppublishing.com/doi/10.3138/jammi-2025-0307 ____

Highlights •  In a landscape of a very narrow arsenal of influenza antivirals, resistance mutations are a significant threat. •  Resistance mutations were present in 0.5-5% in A and B influenza viruses during the last 15 years. •  However, S247N resistance mutation in the NA gene sharply increased during 2023-2024 season. •  While this mutation does not confer strong resistance by itself, their fixation could increase the risk of resistance in the future if other resistance mutations appears or get fixed together with it. Abstract The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations , especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain . To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences , and analyzed the resistance m...

Highlights •  Antiviral susceptibility to NA inhibitors and PA inhibitor baloxavir was determined for seasonal and zoonotic influenza viruses circulating globally during 2020–2023. •  Low global frequencies (0.1-0.2%) of seasonal influenza viruses with reduced or highly reduced inhibition by NAI inhibitors were observed as in previous years. •  Low global frequencies of seasonal influenza viruses (∼ 0.1%) with reduced susceptibility to baloxavir were observed, with the rate in Japan elevated (3.3%) in 2022–2023, as has been seen previously. •  For zoonotic viruses, 2.7% contained genetic markers associated with reduced or highly reduced inhibition to NA inhibitors and none contained markers associated with reduced susceptibility for baloxavir. •  For the treatment of influenza , NA inhibitors and baloxavir remain suitable. ABSTRACT Antiviral susceptibility of influenza viruses is monitored by the World Health Organization Global Influenza Surveillance and Respon...

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 ____