ETIDIOH - NEW

  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 Human (avian) influenza A viruses, especially highly pathogenic avian influenza (HPAI) viruses, pose a significant public health threat , and a multivalent vaccine is the primary prophylactic measure to control these viruses. To establish such a vaccine, we generated two multivalent vesicular stomatitis virus (VSV)-based vaccine candidates (V-EtM2e/H505 and V-EtM2e/H522) and characterized their ability to induce protective immune responses. Our results revealed that vaccine immunization in mice induced high humoral immune responses against both the HPAI hemagglutinin (HA) protein and the ectodomain of M2 (M2e) protein . Intriguingly, vaccine-immunized mouse sera exhibited highly efficient neutralizing activity against the corresponding H5 pseudovirus and mediated potent and broad antibody-dependent cellular cytotoxicity (ADCC) activity against M2e derived from human and avian influenza H5, H1, H3, and H7 viruses . Furthermore, both intranasal and intramuscular immunizati...

  Abstract The global spread of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses has recently extended to include diverse mammalian species , raising new concerns about pandemic risk . In 2023, this clade was first detected in Russian marine mammals during a mass mortality event among northern fur seals in the Far East . Genetic analyses revealed the causative viruses to belong to genotype A3 of European origin , which is known to have circulated in wild birds across the Far East since 2022. Notably, these isolates harbor the mammalian-adaptive substitutions PB2-K482R and NP-N319K—mutations previously linked to enhanced virulence in non-H5 avian influenza viruses , but whose impact on A(H5N1) clade 2.3.4.4b viruses remained to be characterized. The heightened virulence of A3 genotype viruses is confirmed by data obtained via a mouse model . However, despite these adaptive changes, ferret transmission models showed no evidence of airborne transmission of the fur seal...

  {Excerpt} Since 1997, more than 1000 cases of highly pathogenic avian influenza A(H5N1) have been reported in humans . During this time, A(H5N1) viruses have evolved into dozens of clades , showing ever-expanding phylogenetic diversification and geographical spread . Over the past 5 years, clade 2.3.4.4b A(H5N1) viruses have exhibited rapid global expansion in migratory birds, with spillover to an increasing range of marine and terrestrial mammalian species . Among these species are dairy cattle , not previously recognised as a permissive host for influenza A viruses (IAV), leading to widespread clade 2.3.4.4b A(H5N1) outbreaks in herds in the USA and sporadic human infections linked with exposure to infected animals since March 2024. While person-to-person transmission has not been detected in the USA, the increased geographical distribution of and susceptibility of mammalian hosts to clade 2.3.4.4b A(H5N1) viruses has brought to the forefront a need to assess the pandemic risk ...

  Summary Background Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans . Cross-species transmission events to mammals, including humans , in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells . Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response. Methods In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1Gull2022, H5N1Polecat2022, and H5N1Bovine2024) in comparison with previously studied 2....

  Highlights •  Epidemiological parameters differ by pathogen and by setting. •  Unsupervised machine learning classifies pathogens into distinct epidemiological archetypes. •  Pathogens can be allocated into defined groups outlining plausible parameter ranges across epidemiologically similar pathogens. Abstract Introduction In the light of the COVID-19 pandemic many countries are trying to widen their pandemic planning from its traditional focus on influenza . However, it is impossible to draw up detailed plans for every pathogen with epidemic potential. We set out to try to simplify this process by reviewing the epidemiology of a range of pathogens with pandemic potential and seeing whether they fall into groups with shared epidemiological traits. Methods We reviewed the epidemiological characteristics of 19 different pathogens with pandemic potential (those on the WHO priority list of pathogens, different strains of influenza and Mpox). We extracted data on key pa...

  Abstract Zoonotic spillover of influenza A viruses into humans has repeatedly triggered pandemics throughout history. Since their emergence in the 1990s, H5N1 influenza viruses have significantly expanded their geographical range and host species , raising global concern about the potential for sustained human-to-human transmission . In this review , we examine the virological characteristics of currently circulating H5N1 strains, key molecular barriers limiting their spread among humans, and critical areas of future research to mitigate the ongoing H5N1 panzootic and prevent future pandemics. Source:  Link:  https://academic.oup.com/immunohorizons/article/9/SI/vlaf062/8381786 ____

  Abstract The unprecedented 2.3.4.4b. A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat. Population immunity is a critical component of influenza pandemic risk assessment . We assessed the pre-existing cross-reactive immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5–88 yrs) in multiple US geographic regions during 2021–2024. Pre-existing neutralizing and hemagglutinin (HA)-head- binding antibodies to A(H5N1) were low , but there were substantial cross-reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1). Antibodies to group 1 HA stalk were also prevalent and increased with age . A(H1N1)pdm09 infection and influenza vaccination did not induce neutralizing antibodies to A(H5N1) viruses but induced significant rise of functional NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies . Moreover, pre-pandemic stockpiled 2.3....

{Summary} Context   Over five years since the detection of the first COVID-19 cases , SARS-CoV-2 continues to circulate globally, causing acute illness, hospitalization, and death , alongside prolonged negative impacts on individuals, health systems , and economies , including post-COVID-19 condition (PCC or Long COVID).  While global population-level immunity has increased significantly through both infection and vaccination, the virus continues to evolve, challenging control efforts and underscoring the need for long-term, sustainable disease management .  Confirming earlier warnings from MERS-CoV and SARS-CoV-1 , SARS-CoV-2 has demonstrated the pandemic potential of coronaviruses , which remain one of the most consequential infectious disease threats of our time .  Purpose of the strategic plan   This plan sets out WHO’s strategic framework to support Member States in the sustained, integrated, evidence-based management of coronavirus disease threats , includ...

  Abstract The global spread of highly pathogenic avian influenza A(H5N1) viruses poses a serious pandemic threat . While sustained human-to-human transmission has not occurred, widespread circulation in birds , increased detection in mammals , and occasional human spillovers underscore the need for safe and effective vaccines . We evaluated an H5 mRNA vaccine candidate in ferrets using recent clade 2.3.4.4b A(H5N1) human isolates. Vaccination elicited strong neutralizing antibodies , conferred robust protection against lethal challenge , and significantly reduced viral titers . In a direct contact transmission model , mRNA vaccination decreased virus shedding in inoculated ferrets and reduced onward transmission ; it also protected vaccinated contact ferrets from infection following exposure to virus-shedding, unvaccinated ferrets. Additionally, sera from vaccinated animals cross-neutralized clade 2.3.2.1e human viruses to varying degrees, depending on the strain. These findings d...

  Abstract Highly pathogenic avian influenza (HPAI) H5 viruses have recently been documented in mammals including humans , posing a major threat to global public health . To prevent a potential H5 pandemic , it is critical to elucidate the antigenic evolutionary pattern and identify key drivers underlying its evolution . In this work, we construct a comprehensive antigenic map of H5 influenza viruses spanning their evolutionary history and classified three antigenic clusters with no cross-neutralization . The first corresponds to ancestral clades, the second to 2.3.4.4* clades being predominant since 2010, and the third to 2.3.4.4 h clade. Despite the gradually increasing genetic distances from ancestral to 2.3.4.4* to 2.3.4.4 h, their antigenic evolution does not follow the same progressive pattern: the antigenic distance between 2.3.4.4 h and ancestral is smaller than that between 2.3.4.4* and ancestral . This divergence is associated with two distinct mutation patterns at six ke...

  Abstract Understanding the geographic spread of emerging respiratory viruses is critical for pandemic preparedness , yet the early spatiotemporal dynamics of the 2009 H1N1 pandemic influenza and SARS-CoV-2 in the United States (US) remain unclear . While mobility and genomic data have revealed important aspects of pandemic spatial spread, several key questions remain: Did the two pandemics follow similar spatial transmission routes? How rapidly did they spread across the US? What role did stochastic processes play in early spatial transmission? To address these questions, we integrated high-resolution disease data with a robust, data-efficient inference framework combining air travel, commuting flows, and pathogen superspreading potentials to reconstruct their spatial spread across US metropolitan areas . The two pandemics exhibited distinct transmission pathways across locations; however, both pandemics established local circulation in most metropolitan areas within weeks , driv...

  Abstract Influenza A virus (IAV) has a wide range of avian and mammalian hosts, leading to disease outbreaks and increasing the risk of panzootics and pandemics . Subtype H5N1 of clade 2.3.4.4b is causing the current high pathogenicity avian influenza (HPAI) panzootic . Environmental changes are fuelling the spread of HPAI H5N1 in wildlife worldwide, with occasional spillover events from seabirds to cetaceans . Sampling difficulties and limited tests available for diagnosis are a challenge to cetacean virology research . Understanding the risk of HPAI outbreaks in cetaceans requires a comprehensive examination of events of IAV infection. Documented cases relate to IAV subtypes H1N3, H13N2, H13N9, and H5N1 and have been reported in cetaceans sampled in the Pacific, Atlantic, and Arctic Oceans . The number of H5N1 IAV isolated from cetaceans is increasing and affects six host species of the families Delphinidae and Phocoenidae of the suborder Odontoceti . The analysis of 40 molecul...

  Abstract Most emerging human infectious diseases are derived from animals , and monitoring such zoonoses is imperative to help prevent future outbreaks . In this Forum , we discuss the knowledge gaps in our current understanding of viral ecology, global disparities in virus discovery , and the applications of artificial intelligence in infectious disease monitoring. Source: Cell Host & Microbe,  https://www.cell.com/cell-host-microbe/abstract/S1931-3128(25)00429-9?rss=yes ____

  Summary -- What is already known about this topic? - The H3N8 avian influenza virus (AIV) demonstrates considerable capacity for interspecies transmission and has been documented in multiple mammalian hosts , including equine and canine species. During 2022–2023, three laboratory-confirmed human infections with H3N8 were reported in China, heightening public health concerns about the zoonotic spillover potential of H3 subtype AIVs. -- What is added by this report? - This study reports the isolation of a genetically reassorted, low-pathogenicity H3N8 avian influenza virus (AIV) from an islet in Niukouyu Wetland Park, Beijing Municipality — the first detection of this viral strain in a wild environment within the city. Throat swabs collected from park staff tested negative for influenza viruses. Phylogenetic analysis demonstrated that the viral hemagglutinin gene originated from the Eurasian lineage, while the neuraminidase gene was derived from the North American lineage . Althoug...

  Abstract Influenza pandemics arise when novel influenza virus subtypes emerge in populations with little or no pre-existing immunity . The recent expansion of H5N1 virus circulation in mammals — including documented spread in cattle and sporadic human infections — coupled with the emergence of mutations associated with enhanced pandemic potential , underscores the persistent threat of novel influenza strains. Pandemic preparedness critically depends on developing effective vaccines capable of providing broad protection across diverse viral strains. While vaccination remains the most effective strategy for preventing influenza and its complications, pandemic vaccine development faces substantial challenges . These include the rapid mutation rates characteristic of influenza viruses, driven by error-prone RNA replication, broad host range, environmental selection pressures, and frequent genetic recombination. Such factors complicate predictions of which strain will trigger the next...

  Abstract Infectious diseases are often observed to have different epidemiology in different countries , which arises due to various factors including those that are ecological, socioeconomic, and healthcare-related . Such variability can sometimes be best captured through looking at groups of countries that are similar within-group but variable between-group. In this study we use statistical learning methods to generate data-driven disease-centric groupings of countries rather than those developed for administrative or political reasons by e.g. the WHO, World Bank, and the United Nations. In particular, we apply hierarchical clustering to group countries based on shared disease-relevant characteristics for zoonotic H5N1 influenza . Using statistical methods such as classification and regression trees (CART)-based imputation and dynamic tree cutting, the analysis accounts for missing data and identifies epidemiologically (rather than politically or economically) meaningful cluster...

  September 2025   The development of influenza candidate vaccine viruses (CVVs), coordinated by WHO, remains an essential component of the overall global strategy for influenza pandemic preparedness . Selection and development of CVVs are the first steps towards timely vaccine production and do not imply a recommendation for initiating manufacture . National authorities may consider the use of one or more of these CVVs for pilot lot vaccine production , clinical trials and other pandemic preparedness purposes based on their assessment of public health risk and need.  Zoonotic influenza viruses continue to be identified and evolve both antigenically and genetically, leading to the need for additional CVVs for pandemic preparedness purposes.  Changes in the antigenic and genetic characteristics of these viruses relative to existing CVVs and their potential risks to public health justify the need to develop new CVVs. This document summarizes the antigenic and genetic c...

  Abstract The SARS outbreak and influenza A(H5N1) infections (2003–2004) prompted WHO to establish a global influenza antiviral stockpile , enabling rapid distribution to 72 countries during the 2009 A(H1N1) pandemic. To improve access in low- and middle-income countries, WHO added antivirals to the WHO Model List of Essential Medicines and included them in the Prequalification Programme . The 2011 Pandemic Influenza Preparedness Framework refined strategies for equitable access and rapid response. Lessons from COVID-19 led to a new WHO-led mechanism—the Interim Medical Countermeasures Network (i-MCM-net)— which supports integrated supply chains, real-time data sharing, research and development, and equitable access. WHO continues to emphasise equity and global solidarity , highlighting the need for accessible, effective, and affordable antivirals alongside vaccines to protect vulnerable populations and mitigate the impact of future pandemics. Source: Journal of Infectious Disease...