ETIDIOH - NEW

  Abstract In China, low pathogenic avian influenza (LPAI) H3N8 virus is widespread among chickens and has recently caused three zoonotic infections , with the last one in 2023 being fatal . Here we evaluated the relative pandemic risk of this 2023 zoonotic H3N8 influenza virus, utilizing our previously published decision tree. Serological analysis indicated that a large proportion of the human population does not have any cross-neutralizing antibodies against this H3N8 strain. LPAI H3N8 displayed a dual affinity for a2-3 and a2-6 sialic acids and replicated efficiently in human bronchial epithelial cells . Furthermore, we observed H3N8 transmission via direct contact but not aerosols to ferrets with pre-existing H3N2 immunity. Although pre-existing H3N2 immunity resulted in a shortened disease course in ferrets, it did not reduce disease severity or replication in the respiratory tract. This study suggests that this zoonotic H3N8 strain has moderate pandemic potential and emphasiz...

  Abstract In 2024, a human infection with clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) virus was identified in the United States in an individual with no known exposure . Genetic analysis revealed two hemagglutinin (HA) substitutions, P136S and A156T, which may alter viral antigenicity . Virus isolation was unsuccessful, preventing timely serologic analysis. To overcome this limitation, we generated recombinant viruses by reverse genetics and characterized the effects of the substitutions on antigenicity, receptor binding , and replicative fitness. The A156T substitution introduced a potential N-linked glycosylation site , resulting in altered antigenicity and reduced replication in primary human nasal epithelial cells and ferrets . Importantly, the A(H5N1) candidate vaccine virus (CVV) IDCDC-RG80A, which possesses HA-T156, remained antigenically effective against viruses with and without these substitutions. These findings highlight the importance of sequencing, rever...

  {Excerpt} Highly pathogenic avian influenza caused by H5N1 viruses emerged in East Asia in the late 1990s and spread to Europe, Africa, and the Middle East , circulating in wild and domestic birds and occasionally spilling over into mammals and humans . These viruses are classified into genetic lineages called clades based on differences in the gene encoding hemagglutinin , a key surface protein involved in cell entry. In 2021, one such lineage, clade 2.3.4.4b , crossed from Europe to Canada . It spread rapidly, reaching the southern tip of South America in less than 2 years and causing massive mortality in seabirds and marine mammals , including South American sea lions (Otaria flavescens) and southern elephant seals (Mirounga leonina) (1). However, human mortality has been markedly lower in the present H5N1 outbreak than in past ones. If the virus evolves the capacity to transmit from human to human, understanding this reduction will be essential for mounting an effective respo...

  ABSTRACT Given the recurring threat of coronavirus outbreaks, understanding the specificity of coronaviruses in terms of their host, tissue, and cell tropism is crucial . This review consolidates and critically assesses the current literature on the tropism of endemic, epidemic, and pandemic coronaviruses . We explore different levels of tropism , including species tropism (virus preference for specific host species), host cell tropism (virus specificity for particular cell types), and tissue tropism (specificity for certain tissues or organs). This review compiles extensive basic research, particularly from recent years, to provide critical insights into the viral mechanisms that are key to improving future pandemic preparedness. Source: mBio,  https://journals.asm.org/doi/10.1128/mbio.02437-25 ____

  ABSTRACT Influenza A viruses continuously circulate among avian and swine species, posing a persistent threat to public health . The development of influenza candidate vaccine viruses (CVVs) plays a pivotal role in the global strategy for influenza pandemic preparedness . Safety-testing of CVVs for attenuation in ferrets represents a critical step that takes place prior to making these viruses available to vaccine manufacturers . Development of pathogenicity standards is needed to establish acceptable thresholds of disease so that CVV safety can be assessed without the need for comparison to the parental virus. To assess the capacity of diverse CVVs to cause pathogenesis in mammalian hosts , clinical and virological parameters were compiled from CVV assessments in ferrets conducted using consistent methods over approximately 20 years to identify disease parameters most reflective of attenuation compared to wild-type strains. These analyses revealed an overall reduction in ferret ...

  New human cases {1,2}:  -- From 2 July to 25 August 2025 , based on reporting date, the detection of influenza A( H5N1 ) in five humans and influenza A(H9N2) in two humans were reported officially.   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}  Risk assessment {5}:  - Sustained human to human transmission has not been reported from these events.  - Based on information available at the time of this risk assessment update , the overall public health risk from currently known influenza A viruses detected at the human-animal interface has not changed and remains low .  - The occurrence of sus...

  09/09/2025 -  Foz do Iguaçu, Brazil  In an unprecedented response to the rapid global spread of high pathogenicity avian influenza (HPAI), stakeholders and experts from across the poultry sector, public health, science, and policy spheres have convened in Brazil in a landmark meeting .  This first-ever global multisectoral dialogue aims to forge coordinated defense against the escalating threat to animal and human health and agricultural livelihoods. Avian influenza, commonly known as bird flu , is a highly contagious viral disease that primarily infects birds. The virus belongs to the Type A influenza family, which is known for its ability to mutate and change rapidly. Since 2020, HPAI has expanded rapidly across continents , devastating poultry flocks , impacting biodiversity , trade and food security , and raising concerns over its potential to spark a human pandemic . The currently circulating avian influenza panzootic is now widespread, and represents one of t...

  Highlights •  The H5N1 influenza virus-like particle vaccines are prepared through baculovirus expression vector system. • In vitro assessments have confirmed that this VLP vaccine has the correct conformation and functional activity. • This VLP vaccine induces robust humoral and cellular immune responses in mice , and provides complete protection against infection with the matched strain. Abstract Avian influenza virus infections pose a potential pandemic threat . The currently licensed vaccines have inherent limitations, emphasizing the urgent need for improved influenza vaccines. Here, we developed a novel hemagglutinin (HA) virus-like particle (VLP) vaccine candidate through the baculovirus expression vector system (BEVS). The engineered VLPs incorporate HA from H5N1 and matrix 1 (M1) protein from H1N1 . Comprehensive characterization revealed that purified HA VLPs exhibited morphological fidelity to native influenza virions while maintaining key viral biological propert...

  Abstract Highly Pathogenic Avian Influenza (HPAI) is a prominent candidate for a future human pandemic arising from a zoonotic spillover event . Its best-known subtype is H5N1 , with South- or South-East Asia a likely location for an initial outbreak. Such an outbreak would be initiated through a primary event of bird-to-human infection, followed by sustained human-to-human transmission . Early interventions require the extraction, integration and interpretation of epidemiological information from the limited and noisy case data available at outbreak onset. We studied the implications of a potential zoonotic spillover of H5N1 influenza into humans . Our simulations used BharatSim , an agent-based model framework designed primarily for the population of India , but which can be tuned easily for others. We considered a synthetic population representing primary contacts in an outbreak site with infected birds. These primary contacts transfer infections to secondary ( household) cont...

  Abstract Background   The ongoing H5N1 panzootic in mammals has amplified zoonotic pathways to facilitate human infection . Characterising key epidemiological parameters for H5N1 is critical should it become widespread.  Aim   To identify and estimate critical epidemiological parameters for H5N1 from past and current outbreaks, and to compare their characteristics with human influenza subtypes and the 2003 Netherlands H7N7 outbreak.  Methods   We searched PubMed, Embase, and Cochrane Library for systematic reviews reporting parameter estimates from primary data or meta-analyses. To address gaps, we searched PubMed and Google Scholar for studies of any design providing relevant estimates. We estimated the basic reproduction number for the recent outbreak in the United States (US) and the 2003 Netherlands H7N7 outbreak. In addition we estimated the serial interval for H5N1 using data from previous household clusters in Indonesia. We also applied a branching...

Abstract The continuous evolution and widespread dissemination of highly pathogenic avian influenza (HPAI) H5N1 viruses , particularly clade 2.3.4.4b, pose critical challenges to global pandemic preparedness . In this study, we assessed a low-dose inactivated split virus vaccine derived from clade 2.3.4.4b H5N1, formulated with an Alum/CpG adjuvant , using a preclinical mouse model . This vaccine induced potent humoral and cellular immune responses , generating high titers of cross-reactive antibodies targeting both hemagglutinin (HA) and neuraminidase (NA) glycoproteins across homologous and heterologous H5 clades. The Alum/CpG adjuvant enabled significant antigen dose-sparing while promoting a balanced Th1/Th2 immune profile . Functional analyses demonstrated strong virus neutralization , neuraminidase inhibition, and potent antibody-dependent cellular cytotoxicity activity . Additionally, the vaccine elicited robust antigen-specific CD4+ and CD8+ T cell responses and effectively con...

  ABSTRACT The mammary gland is an essential organ for milk production, providing essential immune and nutritional support to offspring and supplying dairy products for human consumption. In both humans and animals , the lactating mammary gland is susceptible to bacterial and viral infections , which can lead to mastitis and, in some cases, vertical transmission to offspring , with potential adverse effects on infant health. However, until recently, the role of respiratory viruses in mammary gland infection has been relatively understudied, particularly their ability to infect mammary epithelial cells and transmit through lactation. The recent emergence of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in dairy cattle has demonstrated the virus’s capacity to replicate in the mammary gland, cause mastitis, and produce high viral loads in milk . This raises significant concerns about the potential for zoonotic transmission to humans and other animals in contact with infected d...

ABSTRACT The 2.3.4.4b clade highly pathogenic avian influenza H5N1 infected diverse non-human mammalian species , gained mammal-to-mammal transmission potential , and caused sporadic human infections . However, whether non-human mammals enable the human adaptation of 2.3.4.4b H5N1 to establish human infections is unclear. Gain-of-function research restrictions may hinder the assessment of 2.3.4.4b H5N1 human adaptations. Here, we tracked the evolution of 2.3.4.4b H5N1 that infected non-human mammals and evaluated their ability to gain human adaptations. The non-human mammal 2.3.4.4b H5N1 partly acquired classical human-adapting mutations , which are identical to the residues of H1N1pdm09 and seasonal human H3N2 viruses, while showing a few species-specific adaptations that might be potential barriers for successful human infections. The polymerase complex proteins , PA and PB2, acquired human adaptations in non-human mammals, with fox-infected viruses showing more positive selection in...

Abstract The study aimed to assess the impact of the COVID-19 pandemic on breast cancer diagnosis, tumor characteristics, and staging in an Eastern-European country . This retrospective study included 11,635 breast cancer patients and clients presenting between March 2019 and March 2022. Patients were categorized into pre-pandemic, pandemic, and post-pandemic groups . Data included age, sex, pathology, tumor characteristics (histologic type, grade, ER/PR/HER2 status), and TNM staging . Statistical analysis compared these parameters across the three-time intervals. During the pandemic, breast cancer diagnosis decreased significantly compared to the pre-pandemic period (9.1% vs. 13.17%, p < 0.001) but increased post-pandemic (11%, p = 0.013). Invasive ductal carcinoma of non-special type (IDC-NST) was predominant in all three-time periods. Aggressive tumors (Nottingham grade 3, ER negative) increased during the pandemic and post-pandemic times . Molecular subtypes showed variations ac...

  Abstract Importance :  Highly pathogenic avian influenza (HPAI) A H5N1 has been recognized for nearly three decades as a threat to avian species and as a virus with pandemic potential if spillover into human populations occurs. Recently the virus has evolved capacity to infect many mammalian species , including dairy cattle , increasing the risk for human exposure and the pandemic threat. Sialic acids (SA) serve as binding sites for influenza viruses. The distribution of SA determines infectivity of specific influenza viruses across species and tissue tropism . Hemagglutinin (HA) of human and swine adapted influenza viruses bind primarily to SA with α2,6-galactose linkages and avian influenza viruses preferentially bind to SA with α2,3-galactose linkages . Recently, the bovine udder was found to contain SA with α2,3 linkages which allow the H5N1 virus to bind to bovine udder epithelium and to infect milk. The distribution of SA receptors in the human mammary gland is unknown...

ABSTRACT Seasonal influenza causes 290,000–650,000 deaths annually, with vaccination efficacy ranging from 10 to 60%. The emergence of drug-resistant and highly pathogenic avian influenza viruses underscores the urgent need for novel protective strategies . Epidemiological observations have long suggested that certain vaccines, such as Bacillus Calmette-Guérin (BCG), can provide protection against diverse pathogens (S. Biering-Sørensen, P. Aaby, N. Lund, et al., Clin Infect Dis 65:1183–1190, 2017, https://doi.org/10.1093/cid/cix525 ; M.-L. Garly, C. L. Martins, C. Balé, et al., Vaccine 21:2782–2790, 2003, https://doi.org/10.1016/s0264-410x(03)00181-6 ; C. A. G. Timmermann, S. Biering‐Sørensen, P. Aaby, et al., Trop Med Int Health 20:1733–1744, 2015, https://doi.org/10.1111/tmi.12614 ). While the cellular and molecular mechanisms underlying such protection remain incompletely understood, emerging research offers critical insights into innate immune system modulation (B. Cirovic, L. C. J...

Abstract Transmission of highly pathogenic avian influenza from H5 clade 2.3.4.4b has expanded in recent years to infect large populations of birds and mammals , heightening the risk of a human pandemic . Influenza viruses adapted to transmission in birds and some other animals tend to have a less stable hemagglutinin (HA) than seasonal influenza viruses , enabling membrane fusion at comparatively high pH levels. Here, we combine five mutations within H5 HA that dramatically increase its melting temperature and promote stable closure of the HA trimer . Structural analysis by cryo-electron microscopy revealed that the stabilizing mutations create several new hydrophobic interactions , while maintaining local HA structure. We found that vaccinating mice with stabilized H5 HA immunogens resulted in higher hemagglutination inhibition and neutralization titers than non-stabilized comparators. Epitope mapping of vaccine-elicited polyclonal antibody responses using negative stain electron mic...

Abstract Highly Pathogenic Avian Influenza (HPAI) viruses, particularly H5N1 and H7N9, have long been considered potential pandemic threats , despite the absence of sustained human-to-human transmission. However, recent outbreaks in previously unaffected regions , such as Antarctica, suggest we may be shifting from theoretical risk to a more imminent threat . These viruses are no longer limited to avian populations. Their increasing appearance in mammals , including dairy cattle and domestic animals , raises the likelihood of viral reassortment and mutations that could trigger a human pandemic. If such a scenario unfolds, the world may face a crisis marked by high transmissibility and lethality, without effective vaccines readily available. Unlike the COVID-19 pandemic, when vaccines were rapidly developed despite inequities in access, the current influenza vaccine production model , largely reliant on slow, egg-based technologies, is insufficient for a fast-moving outbreak. While newe...

  Key points   -- At the present time , based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5) viruses to be low , while the risk of infection for occupationally or frequently exposed (e.g., with backyard poultry) persons is low to moderate depending on the risk mitigation and hygiene measures in place and the local avian influenza epidemiological situation.  -- Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level , at the present time, is considered minor . The assessment could change if and when additional epidemiological or virological information becomes available.  -- This risk assessment from FAO, WHO and WOAH updates the assessment ...