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#H5N1 Avian #Influenza: A Narrative #Review of Scientific Advances and #Global #Policy Challenges

Abstract The H5N1 avian influenza virus continues to evolve into genetically diverse and highly pathogenic clades with increased potential for cross-species transmission . Recent scientific advances have included the development of next-generation vaccine platforms , promising antiviral compounds , and more sensitive diagnostic tools , alongside strengthened surveillance systems in both animals and humans. However, persistent structural challenges hinder global readiness. Vaccine production is heavily concentrated in high-income countries, limiting equitable access during potential pandemics. Economic and logistical barriers complicate the implementation of control strategies such as vaccination, culling, and compensation schemes. Gaps in international coordination , public communication, and standardization of protocols further exacerbate vulnerabilities. Although sustained human-to-human transmission has not been documented, the severity of confirmed infections and the rapid global s...

{A family cluster of cases:} #Mother, #son contract #H5N1 #birdflu in #Cambodia

  PHNOM PENH, June 29 (Xinhua) -- A 46-year-old Cambodian mother and her 16-year-old son have been confirmed positive for H5N1 human avian influenza, bringing the total number of cases to 10 so far this year, the Ministry of Health said in a statement on Sunday. Both victims live in Lbeuk village of Puok district in northwest Siem Reap province. "According to queries, there were sick and dead poultry at the patients' home and their neighbors' homes as well as in the village, and the patients had been in contact with sick and dead chickens and cooked them for food," it added. Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victims in order to prevent an outbreak in the community. Tamiflu (oseltamivir), an antiviral drug to prevent the bird flu from spreading, was also given out to people who had direct contact with the patients, the statement said. So far this year, the ki...

Detection of clade 2.3.4.4b #H5N1 high pathogenicity avian #influenza virus in a #sheep in #UK, 2025

Abstract Clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) continues to pose a significant global threat , affecting wild and domestic avian populations, and mammalian species . In early 2024, H5N1 HPAIV was detected in dairy cattle in the United States of America, where it has continued to circulate, with sporadic detections also reported in other ruminant species . The detection of high viral loads in milk from infected cattle, has resulted in several human infections , underscoring the zoonotic potential of these viruses. In response, several countries have intensified surveillance in non-avian species to evaluate the potential for undetected viral circulation in captive mammals. In Great Britain, bulk milk tank testing of cattle and targeted surveillance of captive mammalian species on an infected premises is undertaken in accordance with the outcome of a rapid risk assessment undertaken to determine the epidemiological links between the poultry and captive mamma...

Phylogenetic and #Mutation #Analysis of #Hemagglutinin Gene from Highly Pathogenic Avian #Influenza Virus #H5 Clade 2.3.4.4b in South #America

Abstract The Highly Pathogenic Avian Influenza Virus (HPAIV) H5 clade 2.3.4.4b has caused severe outbreaks in domestic and wild birds worldwide since its emergence in 2014, and especially since 2020, with outbreaks in Europe and North America . The introduction of the virus into South America was reported for the first time in Colombia in October 2022, followed by outbreaks in other South American countries affecting poultry, wild birds, mammals , and humans . In this study, a phylogenetic and mutation analysis of the hemagglutinin (HA) gene of HPAIV H5N1 2.3.4.4b viruses isolated in South America was performed to analyze its evolution and its transmission and zoonotic potential . The analysis shows an increase in the viral effective population size between April and June 2022, which was followed by multiple outbreaks of HPAIV H5N1 clade 2.3.4.4b in South America . Moreover, the virus variants evolved from a recent common ancestor estimated to have existed in June 2017. The mean rate o...

Highly Pathogenic Avian #Influenza Virus A #H5N1 subclade 2.3.4.4 b isolated from a European grey #seal (Halichoerus grypus) is highly virulent in #ferrets

  Abstract Highly pathogenic avian influenza A viruses subtype H5N1 (HPAIV H5N1), subclade 2.3.4.4b infect multiple avian and mammalian species , posing a potential pandemic risk . Here we describe the outcomes of infection of ferrets with a HPAIV H5N1 virus, isolated from a European grey seal in 2023, compared with an older HPAIV H5N1 (A/Indonesia/05/2005). Overall, infection of ferrets with A/grey seal/Netherlands/302603/2023 caused more rapid mortality than infection of ferrets with A/Indonesia/05/2005. Animals developed severe pneumonia and irreversible hypothermia , associated with high levels of virus replication and histopathological changes in the respiratory tract and peripheral organs. As animal models for severe avian influenza virus infections in humans play a key role in the development of intervention strategies against these infections, these findings highlight the importance of using updated ferret models based on circulating virus strains. Source: Journal of Infect...

Production and Immune Response Against #Pandemic #Influenza Candidate #Vaccines as Preparedness Against the Circulating #H5N1 Influenza Viruses

Abstract Background/Objectives : H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern.  Methods :  The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity.  Results :  Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale ...

#Evolution of #antibody cross-reactivity to #influenza #H5N1 #neuraminidase from an N2-specific germline

Abstract The ongoing spread of highly pathogenic avian influenza H5N1 clade 2.3.4.4b virus in animals and occasional spillover to humans have raised concerns about a potential H5N1 pandemic. Although recent studies have shown that pre-existing human antibodies can recognize H5N1 neuraminidase , there is a lack of molecular understanding of how this cross-reactivity develops. Using a phage display antibody library derived from 245 healthy donors , this study isolates an antibody, known as HB420 , that cross-reacts with the neuraminidases of human H3N2 and avian H5N1 clade 2.3.4.4b viruses and confers protection in vivo. Cryo-EM analysis shows that HB420 targets the neuraminidase active site by mimicking sialic acid binding through a single Asp residue. Additionally, the inferred germline of HB420 is N2-specific but acquires cross-reactivity to H5N1 neuraminidase through somatic hypermutations . Overall, our findings provide insights into how neuraminidase antibody evolves breadth, which...

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (US CDC, June 27 '25)

  {Excerpts} Time Period: June 15, 2025 - June 21, 2025 - H5 Detection :  3 sites ( 0.8% ) - No Detection :  367 sites ( 99.2% ) - No samples in last week :  55 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

#Global #update on susceptibilities of #influenza viruses to #neuraminidase #inhibitors and the cap-dependent endonuclease inhibitor #baloxavir, 2020–2023

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...

#UK {#Wales} - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

{Pembrokeshire, Wales} A backyard flock of 120 laying hens . Increased mortality and other clinical signs consistent with avian influenza (AI) were reported. Samples were collected and tested positive for highly pathogenic avian influenza (HPAI) H5N1. Source: WOAH,  https://wahis.woah.org/#/in-review/6579 ____

Highly Pathogenic Avian #Influenza A(#H5N1) Virus: How Far Are We from a New #Pandemic?

Simple Summary The present commentary deals with the pandemic risk brought about by the highly pathogenic avian influenza (HPAI) A(H5N1) virus . Such a pandemic alarm is justified, among others, by the progressively and rapidly expanding range of virus-susceptible hosts , including humans alongside a significant number of domestic and wild avian and mammalian species , several of which appear to be geographically and phylogenetically distant from each other. Despite its well-established zoonotic potential , no clear-cut evidence of a sustained and efficient HPAI A(H5N1) virus interhuman transmission has thus far been reported. Should this happen in a more or less near future, it could pave the way for a new pandemic. Based upon the above, a “ One Health, One Earth, One Ocean ”-focused, holistic approach would be the necessary prerequisite to deal in an appropriate way with the HPAI A(H5N1) virus-associated zoonotic and pandemic risk. Abstract The focus of this commentary is represented...

#Denmark - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

Credit: Wikipedia. By Bengt Nyman from Vaxholm, Sweden - Larus canus 2203, CC BY 2.0,  https://commons.wikimedia.org/w/index.php?curid=49877446 ___ On the 16th of January 2025, a herring gull was found dead near a wildlife care station. The gull was received at National Reference Laboratory on the 13th of May 2025, and samples from the bird tested positive for HPAI H5N1 on the 20th of June 2025. Source: WOAH,  https://wahis.woah.org/#/in-review/6574 ____

Increased #contact #transmission of contemporary #Human #H5N1 compared to #Bovine and Mountain Lion #H5N1 in a #hamster model

Abstract The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the U.S. poses a significant public health threat. To date, 70 human cases have been confirmed in the United States , including two severe cases and one fatality. While suitable animal models are crucial for predicting the potential pandemic risk of newly emerging pathogens in humans, studies investigating contemporary HPAIV H5N1 transmission dynamics remain limited. Here, we investigated the pathogenicity and transmission efficiency of three recent clade 2.3.4.4b H5N1 viruses isolated from a bovine, mountain lion, and a human case using Syrian hamsters . Intranasal inoculation with 104 TCID50 resulted in productive virus replication in the respiratory tract and shedding for all three isolates. Transmission studies showed limited efficiency via direct contact and airborne routes for all three isolates. Although overall transmission was inefficient , the human H5N1 isolate demonstrated relat...

#Cambodia records 7th #human case of #H5N1 avian #influenza in 2025

  PHNOM PENH, June 24 (Xinhua) -- A 41-year-old woman from northwestern Cambodia's Siem Reap province has been confirmed for H5N1 human avian influenza, raising the number of cases to seven so far this year , the Ministry of Health said in a statement Monday night. "A laboratory result from the National Institute of Public Health showed on June 23 that the woman was positive for H5N1 virus," the statement said. "The patient has the symptoms of fever, cough, and dyspnea , and she is currently in critical condition ," it added. According to queries, there were sick and dead chickens at the patient's home and her neighbor's homes, and the patient had been in contact with sick and dead chickens and cooked them for food five days before she felt ill. Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victim in order to prevent an outbreak in the community. Tamiflu (...

Counting Cases, Conserving #Species: Addressing Highly Pathogenic Avian #Influenza in #Wildlife

Abstract Highly pathogenic avian influenza (HPAI) has become a critical threat to wildlife, shifting from a seasonal epizootic to a persistent, year-round panzootic with global consequences . Here, we summarize the origin, evolutionary mechanisms, and expanding host range of the current H5N1 virus (clade 2.3.4.4b) and assess its impact on wildlife . Over the past five years, HPAI has caused the deaths of millions of wild birds , causing dramatic population declines in several seabird species . However, comprehensive quantitative mortality data remain scarce, as existing records are often anecdotal, focus on localized mass die-offs, and thus represent only a fraction of the true magnitude of mortality. This gap in data limits the ability to predict outbreak dynamics and mitigate long-term consequences. Using the Northwestern European Sandwich Tern (Thalasseus sandvicensis) population as a case study, we demonstrate the value of integrating mortality data with ecological, serological and...

Efficacy of #baloxavir marboxil against #bovine #H5N1 virus in mice

Abstract Since the first detection of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b) in U.S. dairy cattle in early 2024, the virus has spread rapidly, posing a major public health concern as the number of human cases continues to rise. Although human-to-human transmission has not been confirmed, experimental data suggest that the bovine H5N1 virus can transmit via respiratory droplets in ferrets , highlighting its pandemic potential . With no vaccines currently available, antiviral drugs remain the only treatment option. Here, we investigate the efficacy of the polymerase inhibitor baloxavir marboxil (BXM) against this virus in mice. We find that early treatment post-infection is effective, but delayed treatment significantly reduces BXM efficacy and increases the risk of BXM resistance, underscoring the importance of timely BXM administration for effective treatment. Source: Nature Communications,  https://www.nature.com/articles/s41467-025-60791-5 ____

Highly pathogenic avian #influenza A (#H5N1) virus outbreaks in South #America in 2022–2024: a comprehensive review of an ongoing #panzootic

Highlights •  Outbreaks of H5N1 clade 2.3.4.4b in South America have challenged animal and public health. •  Outbreaks across South America affect poultry industry and wild species. •  Surveillance strategies with One Health approach for avian flu is needed Abstract The outbreaks of highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b in South America , which began in 2022, have had significant repercussions across the continent and have led to significant challenges in animal and public health . This review explores the virus's transmission across South America, highlighting the spread of this panzootic through migratory birds and its severe impact on the poultry industry and various wild species , including mammals . The underreporting of influenza cases in poultry underscores the need for enhanced national regulations and strategies to promote reporting within the productive sector. Additionally, the review emphasizes the necessity for active case finding and geno...

Man in #Cambodia dies of #H5N1 avian #influenza #H5N1

  PHNOM PENH, June 21 (Xinhua) -- A 52-year-old man from southeastern Cambodia's Svay Rieng province had died of H5N1 human avian influenza , becoming the fifth human death from the virus so far this year , the Ministry of Health said in a press statement on Saturday. "A laboratory result from the National Institute of Public Health showed on June 20 that the man was positive for H5N1 virus ," the statement said. Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victim in order to prevent an outbreak in the community, it added. Tamiflu (oseltamivir), an antiviral drug to prevent the bird flu from spreading, was also given out to people who had direct contact with the patient, the statement said. The Southeast Asian country recorded a total of six human cases of H5N1 so far this year, with five deaths. Source: Xinhua,  https://english.news.cn/asiapacific/20250621/e94aafa92dbc446...

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (CDC, June 20 '25)

  {Excerpt} Time Period: June 01, 2025 - June 07, 2025 - H5 Detection :  4 sites ( 1.1% ) - No Detection :  370 sites ( 98.9% ) - No samples in last week :  73 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

#Inactivation of #Influenza A Viruses (#H1N1, #H5N1) During #Grana-Type Raw #Milk #Cheesemaking: Implications for Foodborne #Transmission Risk

Abstract Background :  The detection of H5N1 highly pathogenic avian influenza virus (HPAIV) in lactating dairy cattle in the United States , with high viral titers in raw milk, has raised concerns about potential zoonotic transmission through the consumption of unpasteurized milk and raw-milk dairy products. While inactivation studies exist for pasteurized milk, data on virus persistence during the manufacture of raw-milk cheeses remain scarce .  Aim :  To evaluate the survival and inactivation of avian influenza viruses (AIV), including both low pathogenic (LPAIV, H1N1) and highly pathogenic (HPAIV, H5N1) strains, during the production and ripening of Grana-type hard cheeses made from raw bovine milk.  Methods :  Experimental cheesemaking was conducted using raw milk artificially contaminated with A-Duck-Italy-281904-2-06 (H1N1; 10 7,75 EID50 per mL) or A-Duck-Italy-326224-2-22 (H5N1 clade 2.3.4.4b; 10 6,75 EID50 per mL). Cheeses were produced in accordance wi...