ETIDIOH - NEW

  Abstract Clade 2.2 H5N1 influenza viruses have caused an unusually high number of human infections , providing a unique opportunity to investigate early molecular steps associated with host adaptation . Although most work has focused on hemagglutinin (HA), the contribution of neuraminidase (NA) to these early adaptive events has remained unclear. By analyzing publicly available sequences from clade 2.2-infected patients , we identified 20 NA mutations and compared their phenotypes to 20 mutations acquired during diversification in primary human airway cells under drug-free conditions. Most patient-derived NA mutations resulted in modest reductions in sialidase activity , keeping activity within a functional range that supported improved replication in α2,6 sialylglycan (α2,6 Sia)-dominant environments , whereas excessive reduction impaired fitness . Notably, the phenotypes of culture-selected and patient-derived mutations were highly concordant , suggesting that these NA changes ...

  Abstract In November 2024, an adolescent female in British Columbia was hospitalized presenting with severe symptoms including respiratory failure due to infection with a novel H5N1 subtype influenza strain (BC24). Using cryogenic electron microscopy (cryo-EM), we show here that the N169 α2,3-linked auto-glycan that is found in the sialic acid binding site of previously studied H5 hemagglutinin (HA) proteins is absent in purified BC24 HA protein , suggesting greatly reduced affinity for α2,3-linked sialosides . Glycan microarray analysis shows that the BC24 HA protein displays reduced or no binding not just to most α2,3-linked sialosides, but also to α2,6-linked sialosides . Full-length BC24 HA expressed in A549 lung alveolar carcinoma cells drives membrane fusion, albeit at significantly lower levels than previous H5 HA proteins, and post-infection sera from the patient display strong binding to BC24 HA and HA proteins from other influenza subtypes. The high virulence of the BC2...

  Summary Highly pathogenic avian influenza A(H5N1) viruses have been circulating among wild birds and are enzootic in poultry in some areas of the world with spillover to a wide range of terrestrial and marine mammals. Since 1997, sporadic animal to human , primarily poultry to human, transmission of highly pathogenic avian influenza A(H5N1) viruses has been reported in 25 countries . More recently there have been locally acquired infections in the Americas due to the 2.3.4.4b clade of the virus. Most of the recently detected human infections in the USA have been relatively mild but there have been cases of critical illness reported in several countries. In this Grand Round we present the first locally acquired highly pathogenic avian influenza A(H5N1) virus infection in Canada , which was in a 13-year-old female, who developed severe disease requiring prolonged critical care . She was infected with a clade 2.3.4.4b, genotype D1.1 virus and developed evidence of cytokine storm and...

  Abstract Here we investigated the pathogenesis and contact transmission of bovine- and human-derived highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b genotype B3.13 viruses in mammalian models . Using reverse genetics , we rescued three naturally occurring viruses : rTX2/24 (bovine-derived), rTexas/37 and rMichigan/90 (both human-derived), and compared their infection dynamics , replication and pathogenicity with the wild-type bovine TX2/24 strain in vitro and in vivo . All four viruses demonstrated comparable replication kinetics in four mammalian cell lines. However, the rMichigan/90 strain exhibited significantly smaller plaques in bovine and human cells . In vivo studies showed that mice infected with any of the viruses succumbed to infection within 4-5 days ; however, mice infected with the rMichigan/90 virus exhibited slightly lower viral replication and shedding compared to the other strains. Similarly, as in the mouse experiments, in hamsters, all viruses indu...

  Abstract In 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle in the USA resulting in spillbacks into poultry, wild birds and other mammals including humans . Here, we present molecular and virological evidence that the cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes that enabled better replication in bovine cells and tissues , as well as cells of other mammals including humans . We find evidence of several mammalian adaptations in cattle including PB2 M631L , which is found in all cattle sequences, and PA K497R , which is found in the majority. Structurally, PB2 M631L maps to the polymerase-ANP32 interface , an essential host factor for viral genome replication. We show that this mutation adapts the polymerase to better interact with bovine ANP32 proteins , particularly ANP32A, and thereby enhances virus replication in bovine mammary systems and primary human airway cultures . We show th...

  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 ...

  ABSTRACT Current U.S. surveillance for highly pathogenic avian influenza A(H5N1) in humans prioritizes individuals with known animal exposures , potentially missing community-acquired infections . To address this gap, we implemented universal H5 subtyping of all influenza A-positive respiratory samples collected within our hospital system , regardless of patient exposure history. Between August 2024 and April 2025, we subtyped 4,488 influenza A-positive samples and identified two cases positive for H5 RNA in Alameda County, California, USA . The first case was a 14-month-old girl with mild respiratory symptoms and no H5N1 exposure risks ; sequencing of the sample revealed an H5 gene closely related to clade 2.3.4.4b, genotype B3.13 viruses circulating in U.S. dairies . The second case was a 79-year-old male, also with no known exposures , whose sample reproducibly tested positive with a high cycle threshold value but could not be confirmed by public health laboratories. Both pati...

  Abstract Selection of advantageous mutations drives the emergence of dominant variants during seasonal influenza epidemics . However, within-host detection of such variants remains rare , limiting our understanding of how selection operates at the scale of individual hosts. In this study, we used a controlled human infection model to examine the within-host evolutionary dynamics in thirteen participants intranasally infected with a seasonal H3N2 influenza A virus . Although this clinical trial is ongoing , our work represents a pre-planned, interim, exploratory analysis. Results in this system were contrasted with those observed in a ferret model of infection. The inoculum, used in both humans and ferrets, carried standing diversity that enabled evaluation of variant trajectories during infection. Although the dynamics were variable among participants, in humans , the minor variants in the PA and NP gene segments tended to increase in frequency as infection progressed. Variant dy...

  Abstract Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic . Heterogeneities in disease severity have been observed in the past and are reported among infected farm workers in the United States . These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies . In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population (#NCT05794412 and #NCT01022905) and assess the effect of AS03-adjuvanted pandemic H1N1 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We detect H5N1 cross-neutralizing antibodies using a vesicular stomatitis virus-based pseudovirus system that correlate well with antibodies inhibiting the spread of authentic H5N1 viruses, anti-group 1 hemagglutinin stalk and anti-trimeric hemagglutinin antibodi...

  Abstract The highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 represent a major threat to animal and public health . The current panzootic with H5 clade 2.3.4.4b has caused numerous, widespread outbreaks in various domestic and wild avian species with high mortalities, massive losses and a high frequency of spillover events to unexpected novel mammalian hosts such as dairy cows . The global H5N1 situation raises serious concerns about zoonotic risks due to effective mammal-to-mammal transmission . Therefore, it is critical to increase surveillance intensity of a broadened species range, particularly at the human-animal interface . For this purpose, reliable and cost-effective serological tools that are easy to perform and suitable for high-throughput screenings are critically needed. The newly developed double antigen ELISA format employing a luminescence-based detection technology has demonstrated to comply with such prerequisites. The assay allowed the detectio...

  Abstract Avian influenza viruses (AIVs), including H5N1 and H7N9, from the Orthomyxoviridae family present substantial public health concerns . The predominant circulating clade 2.3.4.4b has demonstrated enhanced capacity for mammalian adaptation , raising concerns about potential reassortment with human seasonal influenza viruses . Unlike H7N9 ’s limited host range , H5N1 infects birds, various mammals, and humans . Recent concerns include widespread H5N1 infection of U.S. dairy cattle across 18 states , affecting over 1000 herds with 71 human infections (70 H5N1 and 1 H5N5). Key observations include cow-to-cow transmission, viral presence in milk, and transmission to humans , mainly through occupational exposure . Evidence of mammal-to-mammal transmission has been documented in European and Canadian foxes and South American marine mammals . Standard pasteurization effectively inactivates the virus in milk. The continuing mammalian adaptations , particularly mutations like PB2-E...

  Abstract Avian influenza is a global public health threat. Since 2021, the ongoing H5N1 panzootic has brought a major shift in H5Nx epidemiology , including unprecedented spread, wide host range and lack of seasonality . Infections in marine mammals, wildlife and livestock have heightened concern for human-to-human transmission and pandemic potential . Contact tracing and self-isolation are used as public health measures in the UK to manage contacts of confirmed human cases of avian influenza. In this study, we aimed to estimate potential outbreak sizes and evaluate the effectiveness of contact tracing and self-isolation in managing community outbreaks of H5N1 following spillover from birds to people . We characterised contact patterns from an underrepresented agricultural population at high risk of avian influenza exposure through contact with birds (Avian Contact Study). Informed by these realistic social contact data, we modelled outbreak sizes using a stochastic branching pro...

  Abstract Background Oropouche virus (OROV) is an emerging arbovirus primarily transmitted by biting midges and is increasingly recognized as a public health threat in Central and South America . With over 11,000 confirmed cases reported in 2024, a ten-fold increase from the previous year, its transmission dynamics and true burden remain poorly understood due to diagnostic challenges and fragmented surveillance systems. Objective This systematic review and meta-analysis (SRMA) synthesizes OROV prevalence data in humans and summarizes the available data for vectors and animal hosts sampled between 2000 and 2024 to provide updated estimates and identify key surveillance gaps. Methods We systematically searched Web of Science, PubMed, Embase, Medline, and LILACS for OROV seroprevalence and viral prevalence studies in human, insect, and animal populations, published up to September 12, 2024. The review protocol was registered with PROSPERO (CRD42024551000). Studies were extracted in d...

  Abstract Poultry workers in Washington, USA, were infected with highly pathogenic avian influenza A(H5N1) virus and recovered. The viruses were clade 2.3.4.4b genotype D1.1, closely related to viruses causing poultry outbreaks . Continued surveillance and testing for influenza A(H5) clade 2.3.4.4b viruses remain essential for risk assessment and pandemic preparedness of zoonotic influenza viruses. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-1118_article ____

{Excerpt}  Avian influenza A(H9N2) :  -- Guangdong Province :  1) An individual with onset in November 2025.  -- Guangxi Zhuang Autonomous Region :  2) An individual with onset in November 2025.  -- Hubei Province:  3) An individual with onset in November 2025.  (...) Source:  Link:  https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk51.pdf ____

  Influenza at the human-animal interface  Summary and risk assessment, from 6 November to 19 December 2025 {1} -- New human cases {1,2}:  - From 6 November to 19 December 2025, based on reporting date , the detection of influenza A( H5N1 ) in one human , A( H5N5 ) in one human , A( H9N2 ) in seven humans , and an influenza A( H1N1 ) variant virus in one human were reported officially.  - In addition , one human case of infection with an influenza A( H1N2 ) variant virus was detected.  -- Circulation of influenza viruses with zoonotic potential in animals :  - High pathogenicity avian influenza (HPAI) events in poultry and non-poultry animal species continue to be reported to the World Organisation for Animal Health (WOAH).{3}  - The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  - Additionally, low pathogenicity avian influenza viruses as well a...

  Abstract Highly pathogenic avian influenza H5N1 poses an increasing public health risk, particularly following its spillover into dairy cows and associated human infections in the U.S. since March 2024. Here, we systematically identified critical PB2 mutations emerged during avian-to-cattle transmission and subsequent adaptation in cattle , notably PB2 M631L, which conferred pathogenicity in mice comparable to the well-characterized PB2 E627K mutation . Retrospective analysis reveals that PB2 631L also circulated in avian and human H5N1 strains during the 2013–2014 outbreaks in Cambodia and Vietnam . Additional adaptive mutations include established markers ( E627K, Q591R, D701N ), and novel variants ( I647V, G685R, K736R ). These mutations enhance polymerase activity by improving the utilization of both bovine and human ANP32A proteins , thereby increasing viral fitness and pathogenicity in mammals . The convergence of these adaptations highlights the elevated zoonotic risk of c...

  Abstract Highly Pathogenic Avian Influenza (HPAI) viruses, particularly IAV (H5N1), continue to pose a major global threat due to their widespread circulation and high mortality rates in birds. Management of HPAI is complicated by challenges in conserving migratory bird populations, sustaining poultry production, and uncertainties in disease dynamics. Structured decision-making frameworks , such as those based on the PrOACT model, are recommended to improve outbreak response and guide critical actions , especially when HPAI virus (HPAIV) detections occur in sensitive areas like wildlife refuges . Surveillance data from late 2024 to early 2025 show persistent HPAI activity , with 743 detections across 22 European countries and beyond, and notable outbreaks in poultry in nations like Hungary, Iceland, and the UK . The proximity of poultry farms to water sources increases environmental contamination risks. Meanwhile, HPAI A(IAV (H5N1)) and other H5Nx viruses have been detected in a ...