Showing posts with label a/h5n6. Show all posts
Showing posts with label a/h5n6. Show all posts

Monday, May 4, 2026

#Niclosamide Inhibits the #Replication of Highly Pathogenic Avian #Influenza #H5Nx Viruses and Antiviral-Resistant #Mutants

 


Highlights

• Niclosamide blocks the replication of highly pathogenic avian influenza H5 viruses

• Niclosamide is effective against H5 viruses with antiviral-resistant substitutions

• Niclosamide has potential as host-targeting anti-influenza drug


Abstract

The recurrent spillover of highly pathogenic avian influenza (HPAI) H5 viruses into humans represents a major public health concern that is exacerbated by the emergence of drug-resistant viral variants. Host-targeting antiviral approaches, including drug repurposing, offer a promising alternative to conventional virus-directed therapeutics. Here, we evaluated the antiviral activity of niclosamide, an FDA-approved anthelmintic drug, against four HPAI A(H5Nx) viruses, two A(H5N1), one A(H5N6), and one A(H5N8), recently isolated from human cases. Niclosamide inhibited all four viruses in plaque reduction assays with MDCK cells, with low inhibitory concentration 50% (IC50) values (0.68–1.40 μM) and minimal cytotoxicity at effective concentrations. These values were more potent than the IC50 values observed for the RdRp inhibitor favipiravir. Niclosamide treatment plus either baloxavir marboxil or favipiravir resulted in additive or near-additive interactions, as indicated by synergy scores of ±10. Importantly, niclosamide retained antiviral activity against HPAI A(H5Nx) viruses bearing resistance-associated amino acid substitutions (i.e., PA-I38T, baloxavir resistance and PB1-K229R, favipiravir resistance), consistent with its host-directed mechanism of action. Although there are barriers to be overcome such as a narrow therapeutic window, largely attributable to its poor bioavailability and some cytotoxicity, our findings suggest niclosamide has potential as a host-targeting therapeutic option against emerging zoonotic influenza viruses, particularly in settings involving antiviral-resistant escape mutants.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S016635422600080X?via%3Dihub

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Thursday, April 23, 2026

An #NS1-F161L #Substitution Determines #Host-Driven #Virulence Enhancement of #H5N6 Avian #Influenza Virus in #Ducks

 


Abstract

H5 subtype avian influenza virus (AIV) can infect both chickens and ducks, leading to substantial economic losses. Nevertheless, certain strains cause silent infections in ducks. In this study, a goose-origin clade 2.3.4.4h H5N6 AIV was isolated, which caused high mortality in mixed-gender white leghorn chickens but no deaths in mixed-gender mallard ducks. After independent serial in vitro passage in duck embryo fibroblasts (DEFs) and in vivo passage in specific-pathogen-free (SPF) ducks, the DEF-passage 10 (P10) virus induced markedly higher mortality rates and viral loads in SPF ducks compared to the DEF-P1 virus and the original parental virus prior to passage. Similarly, the in vivo-passaged P3 and P4 viruses exhibited significantly higher mortality rates than the P1 virus in SPF ducks, with 100% mortality and markedly increased viral titers in the organs. A whole-genome SNP analysis identified seven high-frequency mutations in the M1, NA and NS1 proteins. The NS1-F161L substitution virus exhibited significantly increased mortality rates, viral loads in multiple tissues, and a robustly induced innate immune response in ducks. Furthermore, dynamic evolutionary variations in the NS1 protein among global H5 avian influenza viruses revealed that the NS1-F161L substitution became dominant in clade 2.3.4.4b viruses in 2021 and subsequent years. Collectively, our findings demonstrate that host-driven adaptation can rapidly increase the pathogenicity of H5N6 AIVs in ducks and identify NS1-F161L as a critical virulence marker. These results offer novel insights relevant to the molecular surveillance, virulence prediction, and risk assessment of circulating H5 AIVs in waterfowl.

Source: 


Link: https://www.mdpi.com/1999-4915/18/5/488

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Wednesday, April 8, 2026

#Genetic and #biological characterization of a #duck-origin clade 2.3.4.4b #H5N6 avian #influenza virus reveals partial #mammalian #adaptation

 


Highlights

• Duck-origin H5N6 virus A/Duck/Jiangsu/628/2022 shares high homology with the human strain A/Yangzhou/125/2022.

• The 628 strain shows mammalian adaptation markers: HA mutations enhance human receptors affinity and NA mutations reduce sensitivity to neuraminidase inhibitors.

• Limited airborne transmission but detectable droplet-mediated spread suggests increased mammalian transmission risk.


Abstract

Clade 2.3.4.4b H5Nx highly pathogenic avian influenza viruses (HPAIVs) have caused extensive outbreaks in poultry worldwide. H5 HPAIVs have caused sporadic but severe human infections in China, representing a persistent zoonotic threat. Here, we identified a duck-origin H5N6 HPAIV (A/Duck/Jiangsu/628/2022) through routine surveillance and assessed its biological characteristics and mammalian pathogenesis. Phylogenetic analysis revealed > 98% nucleotide identity between strain 628 and the concurrent human H5N6 strain A/Yangzhou/125/2022. Molecular characterization identified multiple mammalian adaptation markers: hemagglutinin substitutions (S137A, T160A, T192I) associated with enhanced human receptor binding; neuraminidase mutations (I117T, D198N) linked to reduced neuraminidase inhibitor susceptibility; and polymerase complex changes (PB1-D622G, PA-K142Q) conferring increased mammalian cell replication. In vitro studies demonstrated that 628 virus replicated more efficiently in mammalian than in avian cells and exhibited dual receptor-binding specificity. Mouse pathogenicity assays revealed moderate virulence with progressive lung pathology. Critically, transmission experiments confirmed both direct contact and airborne transmission capabilities of 628 in guinea pigs. These findings demonstrate that circulating H5N6 viruses have acquired partial mammalian adaptation while retaining avian fitness, significantly elevating pandemic potential. Enhanced surveillance of wild bird populations, poultry farms, and live poultry markets is urgently needed to develop effective prevention and control strategies.

Source: 


Link: https://www.sciencedirect.com/science/article/abs/pii/S037811352600146X?via%3Dihub

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Friday, February 6, 2026

A case of avian #influenza #H5N6 presented with secondary #infection in #Anhui Province, #China, 2024

 


Abstract

A case of H5N6 avian influenza was reported in Anhui Province, China. The viral titers in the patient's lungs and pharynx decreased rapidly after oseltamivir treatment, yet it still fatal. The whole genome sequencing suggested that it derived from four distinct sources and classified within the 2.3.4.4b clade.

Source: 


Link: https://www.sciencedirect.com/science/article/pii/S1684118226000034?via%3Dihub

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Friday, January 30, 2026

#Portugal - #Influenza A #H5N6 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL]

 


Di Jiyang Chen - Opera propria, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=15507046

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This event was created to allow the recreation of outbreak ob_164520, previously reported as H5N1 subtype.

Subadult unspecified seagull. In the Portuguese Exclusive Economic Zone. 

Source: 


Link: https://wahis.woah.org/#/in-review/7234

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Tuesday, December 9, 2025

#Korea (Rep. of) - #Influenza A #H5N6 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 


A Common Teal in Jeollanam-do Region.

Source: 


Link: https://wahis.woah.org/#/in-review/7034

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Thursday, July 10, 2025

#Transmission Dynamics of Highly Pathogenic Avian #Influenza #H5N1 and #H5N6 Viruses in Wild #Birds, South #Korea, 2023–2024

Abstract

We analyzed 15 cases of highly pathogenic avian influenza (HPAI) clade 2.3.4.4b virus infections detected in wild birds in South Korea during September 2023–March 2024. We isolated and sequenced 8 H5N1 and 7 H5N6 viruses. We investigated spatiotemporal transmission dynamics by using a Bayesian discrete trait phylodynamic model that incorporated geographic and host species information. Our source–sink dynamics support introductions of H5N1 viruses from northern Japan to South Korea and subsequent spread through multiple regions in South Korea. The H5N6 viruses were most likely introduced into southwestern South Korea and spread northeastward. Wild waterfowl, especially wild ducks, played a key role in transmission of both H5N1 and H5N6 viruses. Our data showed multiple introductions and extensive spread of HPAI clade 2.3.4.4b viruses and bidirectional transmission between Japan and South Korea. Our results highlight the value of enhanced active surveillance for monitoring HPAI viruses, which can provide insight into preventing future outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0373_article

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Sunday, July 6, 2025

#Neuraminidase #imprinting and the age-related #risk of zoonotic #influenza

Abstract

Highly pathogenic avian influenza of the H5N1 subtype has shown recent unprecedented expansion in its geographic and host range, increasing the pandemic threat. The younger age of H5N1 versus H7N9 avian influenza in humans has previously been attributed to imprinted pre-immunity to hemagglutinin stalk (HA2) epitopes shared with group 1 (H1N1, H2N2) versus group 2 (H3N2) influenza A subtypes predominating in the human population before versus after 1968, respectively. Here we review the complex immuno-epidemiological interactions underpinning influenza risk assessment and extend the imprinting hypothesis to include a potential role for cross-protective neuraminidase (NA) imprinting. We compare H5N1 distributions and case fatality ratios by age and birth cohort (as proxy for HA2 and/or NA imprinting epoch) not only to H7N9 but also H5N6 and H9N2 avian influenza, representing more varied conditions of zoonotic influenza relatedness to human subtypes of the past century. We show homosubtypic NA imprinting likely further modulates the age-related risk of zoonotic H5N1 and H9N2, with implications for pandemic risk assessment and response.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.03.25330844v1

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Tuesday, June 24, 2025

#Investigation of #human #infection with #H5N6 avian #influenza cases in #Sichuan from 2014-24: a retrospective study

Abstract

Objective

The objective is to examine the epidemiology and clinical features of human cases infected with H5N6 avian influenza in Sichuan Province from 2014 to 2024, and to offer guidance for the prevention and management of human infections with H5N6 avian influenza.

Methods

Epidemiological survey reports of H5N6 avian influenza cases in Sichuan Province from 2014 to 2024 were compiled, and the epidemiological context and characteristics of 16 human cases infected with H5N6 avian influenza in the province were summarized and analyzed using descriptive epidemiological methods.

Results

From 2014, when the initial human case of H5N6 infection was documented in Sichuan Province, to 2024, there have been 16 human cases of H5N6 avian influenza in the region, resulting in 12 fatalities and a case fatality rate of 75%. The instances were predominantly located in the Chengdu Plain, eastern Sichuan, and southern Sichuan.

Conclusion

Human instances of H5N6 avian influenza in Sichuan Province exhibit no discernible periodicity, and entail significant fatality rates. It is essential to enhance the early diagnosis and treatment of avian influenza cases in medical facilities, prioritize farmers with preexisting conditions who have been in contact with deceased poultry, conduct influenza virus testing promptly, and administer antiviral medications at the earliest opportunity. Simultaneously, we must effectively engage in public awareness and education for the populace, manage poultry scientifically, and prevent direct contact with deceased poultries.

Source: Frontiers in Public Health, https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1603158/full

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Tuesday, May 6, 2025

Unique Phenomenon of #H5 Highly Pathogenic Avian #Influenza Virus in #China: Co-circulation of Clade 2.3.4.4b #H5N1 and #H5N6 results in diversity of H5 Virus

Abstract

Recently, Clade 2.3.4.4b H5N1 virus has been widely prevalent globally. Although no outbreaks of Avian Influenza have occurred in poultry in China recently, Clade 2.3.4.4b H5 virus can still be isolated from wild birds, live poultry markets and environment, indicating the ongoing co-circulation of H5N1 and H5N6 viruses. In this study, phylogenetic analysis of global Clade 2.3.4.4b viruses and 20 laboratory-isolated H5 strains revealed that Chinese H5N1 and H5N6 viruses since 2021 cluster into two distinct groups, G-I and G-II. Bayesian phylodynamic analysis reveals that G-I H5N6 virus has become an endemic virus in China. In contrast, G-II H5N1 virus, with South China as its main epicentre, has been disseminated in China and its surrounding countries, with its transmission more reliant on the connections of wild birds and waterfowl. Reassortment analysis indicates that since 2023, Clade 2.3.4.4b H5 viruses isolated in China have formed seven genotypes. The genome of H5 viruses has undergone changes compared to those previously prevalent in China. Animal experiments have shown that prevalent H5 viruses exhibit significant lethality in chickens. Additionally, certain H5 viruses have shown the capability of systemic replication in mice. It is noted that H5N6 viruses with HA genes derived from H5N1 viruses demonstrate stronger virulence and pathogenicity in chickens and mice compared to G-I H5N6 viruses. Our study indicates that the co-circulation of H5N1 and H5N6 viruses in China has increased the diversity of H5 viruses, making continuous surveillance of H5 viruses essential.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2502005

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Friday, May 2, 2025

#Ecology and #environment predict spatially stratified #risk of #H5 highly pathogenic avian #influenza clade 2.3.4.4b in wild #birds across #Europe

Abstract

Highly pathogenic avian influenza (HPAI) represents a threat to animal and human health, with the ongoing H5N1 outbreak within the H5 2.3.4.4b clade being the largest on record. However, it remains unclear what factors have contributed to its intercontinental spread. We use Bayesian additive regression trees, a machine learning method designed for probabilistic modelling of complex nonlinear phenomena, to construct species distribution models (SDMs) for HPAI clade 2.3.4.4b presence. We identify factors driving geospatial patterns of infection and project risk distributions across Europe. Our models are time-stratified to capture both seasonal changes in risk and shifts in epidemiology associated with the succession of H5N6/H5N8 by H5N1 within the clade. While previous studies aimed to model HPAI presence from physical geography, we explicitly consider wild bird ecology by including estimates of bird species richness, abundance of specific taxa, and "abundance indices" describing total abundance of birds with high-risk behavioural traits. Our projections of HPAI clade 2.3.4.4b indicate a shift in persistent, year-round risk towards cold, low-lying regions of northwest Europe associated with H5N1. Methodologically, we demonstrate that while most variation in risk can be explained by climate and physical geography, adding host ecology is a valuable refinement to SDMs of HPAI.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.07.17.603912v2

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Wednesday, April 23, 2025

Mathematical #modelling of in vitro #replication dynamics for multiple highly pathogenic avian #influenza clade 2.3.4.4 viruses in #chicken and #duck cells

Abstract

The introduction and subsequent detection of highly pathogenic avian influenza (HPAI) in poultry is influenced by the virus replication fitness, transmission fitness, and virulence in poultry. These viral fitness parameters are important for implementing surveillance and control measures for poultry. This study investigates the potential application of an avian in vitro model using primary chicken embryo (CEF) and duck embryo fibroblasts (DEF) to identify the viral fitness for a reference panel of eight dominant HPAI clade 2.3.4.4 virus genotypes: four H5N1 viruses isolated between 2021 and 2024, as well as three H5N8 and one H5N6 virus isolated between 2014 and 2020. Infectious virus titre and cytopathogenicity were measured in the primary cell cultures over time and these data were analysed using a mathematical model which delineates cell populations into susceptible, latent, infectious, and dead compartments. In addition to obtaining traditional virological parameters such as peak virus replication and the time to 50% cell death, eight new parameters, key among those, the infecting time (tinf), generation time (tgen) and basic reproduction number (R0), were estimated using the mathematical model. Collectively, these parameters contribute to virus characterization, enhancing the resolution for comparing genetically similar viruses. This approach can allow for the evaluation of virus virulence, replication fitness, and, ideally, transmissibility fitness across different hosts. This study underscores the potential of integrating avian in vitro models with mathematical modeling and builds towards rapid risk assessments of novel HPAI viruses.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.22.649950v1

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Thursday, April 10, 2025

Avian #influenza A(#H5N6) virus detected during live-poultry #market #surveillance linked to a #human #infection in #Changsha, #China, from 2020 to 2023

Abstract

In November 2022, we reported a fatal case of human infection caused by a highly pathogenic avian influenza A(H5N6) virus bearing a clade 2.3.4.4b HA gene in Changsha City. We investigated the transmission route and distribution of the H5N6 virus in the largest live-poultry market (LPM), which is linked to the human infection. A total of 1357 samples from the LPM were collected for avian influenza A virus detection from 2020 to 2023. The proportion of LPM samples positive for H5 subtype avian influenza virus was 14.30% (194/1357). Sequences of H5N6 (n = 10) and H5N1 (n = 4) avian influenza viruses were obtained from the LPM samples using next-generation sequencing. The complete genome sequence of the H5N6 virus from the human infection case, A/Changsha/1/2022(EPI_ISL_16466440), was determined and analyzed. The PB1 and PB2 segments shared 99.65% and 99.23% sequence identity with A/duck/Hunan/S40199/2021(H5N6) and A/Whooper swan/Sanmenxia/H615/2020(H5N8), respectively. The other segments showed the highest sequence similarity to strain A/Guangdong/1/2021(H5N6), which was isolated in Guangzhou. L89V and I292V substitutions in the PB2 protein were predicted from the A/Changsha/1/2022 genome sequence. Phylogenetic analysis based on the HA gene showed that A/Changsha/1/2022 and other H5 subtype isolates obtained from the LPM grouped together in the 2.3.4.4b branch. Bayesian evolutionary analysis of the HA gene showed that clade 2.3.4.4b of the H5N6 virus is likely to have been prevalent in Hunan Province around October 2021. In conclusion, we confirmed that the clade 2.3.4.4b HA gene of A/Changsha/1/2022 virus recombined with those of local strains. These results demonstrate the importance of continuous surveillance of H5N6 influenza viruses.

Source: Archives of Virology, https://link.springer.com/article/10.1007/s00705-025-06280-y

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Friday, March 28, 2025

#Genetic and #antigenic characteristics of #zoonotic #influenza A viruses and development of candidate #vaccine viruses for #pandemic preparedness {WHO, March 28 '25}

February 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 1 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 characteristics of recent zoonotic influenza viruses and  related viruses circulating in animals1 that are relevant to CVV updates.  Institutions interested in receiving these CVVs should contact WHO at gisrs-whohq@who.int or the institutions listed in announcements published on the WHO website.{2}


Influenza A(H5) 

Since their emergence in 1997, high pathogenicity avian influenza (HPAI) A(H5)  viruses of the A/goose/Guangdong/1/96 haemagglutinin (HA) lineage  have become enzootic in many countries, have infected wild birds  and continue to cause outbreaks in poultry and sporadic human and  other mammalian infections across a wide geographic area. In the United  States of America (USA), an outbreak of HPAI A(H5N1) in dairy cattle has been  reported since March 2024 with 2 additional introductions from wild birds  detected in February 2025. A(H5) HA gene segments have paired with a  variety of neuraminidase (NA) subtypes (N1, N2, N3, N4, N5, N6, N8 or N9).  These viruses have diversified genetically and antigenically, leading to the need  for multiple CVVs. This summary provides updates on the characterization of  A/goose/Guangdong/1/96-lineage A(H5) viruses and the status of the  development of influenza A(H5) CVVs. 


Influenza A(H5) activity from 24 September 2024  to 24 February 2025 

Since 2003, 16 A(H5), 7 A(H5N8), 93 A(H5N6) and 956 A(H5N1) human  infections or detections have been reported. Since 24 September 2024, 60  human infections with A/goose/Guangdong/1/96-lineage viruses have been  reported to WHO. A/goose/Guangdong/1/96-lineage A(H5) viruses have been  detected in both domestic and wild birds with spillover to mammals in many  countries, and sustained circulation in dairy cattle in the USA (...). The  nomenclature for phylogenetic relationships among the HA genes of  A/goose/Guangdong/1/96-lineage A(H5) viruses is defined in consultation with  representatives of WHO, the Food and Agriculture Organization of the United  Nations (FAO), the World Organisation for Animal Health (WOAH) and academic  institutions.{3} There has been a recent update to this nomenclature to reflect  the genetic diversification of the A(H5) viruses, particularly clade 2.3.2.1c, to add  2.3.2.1d, e, f, and g.{4} Where relevant, updated clade nomenclatures have been  adopted in this report. 


Genetic and antigenic characteristics  of influenza A(H5) viruses 

Sixty new human infections or detections with  A/goose/Guangdong/1/96-lineage viruses were reported. Most infected individuals had recent exposure to  birds or dairy cattle. One fatal human infection with a clade 2.3.2.1e A(H5N1)  virus was identified in Cambodia in this period. The HA of the virus recovered  from this individual, A/Cambodia/KSH250004/2025, had 2 amino acid  substitutions relative to the A/Cambodia/ SVH240441/2024 CVV and antigenic  data are pending. One human A(H5) infection from Viet Nam was detected;  no genetic or antigenic data were available for this case. One A(H5N1) virus  detection was reported in the United Kingdom of Great Britain  and Northern Ireland in an individual with recent exposure to infected commercial  poultry. This virus was confirmed as belonging to clade 2.3.4.4b and was  genetically and antigenically similar to existing clade 2.3.4.4b CVVs. One case of  clade 2.3.4.4b virus infection was detected in Canada in a severely ill  individual that ultimately recovered. Although a source of exposure was not  identified, the virus was genetically related to other clade 2.3.4.4b viruses  detected in wild birds and poultry in the region. The HA of the virus had 4 amino  acid substitutions relative to the  A/Astrakhan/3212/2020 CVV. Antigenic analysis  showed the virus reacted well to post-infection ferret antisera raised against the  A/Astrakhan/3212/2020,  A/American Wigeon/South Carolina/22-000345-001/2021, A/chicken/Ghana/AVL-763_21VIR7050-39/2021 and  A/Ezo red  fox/Hokkaido/1/2022 CVVs (Table 2). Fifty-six clade 2.3.4.4b A(H5) human  infections were identified in the USA. All but 2 cases reported exposure to dairy  cattle or poultry in backyard or commercial settings, and most reported mild  illness. One case where underlying comorbidities were present was hospitalized  with pneumonia but recovered. A second case, with prolonged, unprotected  exposure to infected birds in a backyard setting developed severe respiratory  disease leading to a fatal outcome. The HAs of viruses detected in human cases in  the USA and Canada were genetically similar to viruses detected in either dairy  cattle or birds (...) and had between 1 and 6 amino acid substitutions  relative to existing clade 2.3.4.4b CVVs. Most of the viruses tested antigenically  reacted well with ferret antisera raised to the clade 2.3.4.4b CVVs (...). A(H5)  viruses from birds and non-human mammals belonged to the following clades:  Clade 2.3.2.1a viruses were detected in poultry in Bangladesh and in wild birds  and poultry in India. Detections in captive tigers, a captive leopard, and domestic cats were also reported in India. The circulation of clade 2.3.2.1a  viruses in these countries has continued despite the introduction of clade 2.3.4.4b  viruses. The viruses from Bangladesh had HAs genetically similar to those of  viruses detected previously and reacted well with post-infection ferret antisera  raised against the A/duck/Bangladesh/19097/2013 CVV. The HA of viruses  detected in India were genetically related to A/Victoria/149/2024, a virus isolated  from a traveller returning to Australia from India{5} (...). No antigenic data are  available for the viruses collected in India; however, many of the HA amino acid  substitutions they contained were shared  with A/Victoria/149/2024, which  reacted poorly with post-infection ferret antisera raised against available CVVs  (...). Clade 2.3.2.1e viruses were detected in poultry in Cambodia, Lao People’s  Democratic Republic, and Viet Nam and in captive tigers and a captive leopard in  Viet Nam. The HAs of these viruses were similar to viruses detected in previous  periods in the region. Viruses from Lao People’s Democratic Republic and Viet Nam  were characterized antigenically. The viruses from Lao People’s Democratic  Republic reacted well with post-infection ferret antisera raised against  A/Vietnam/KhanhHoaRV1-005/2024, a A/Cambodia/SVH240441/2024-like virus  that is under development as a CVV. The viruses from Viet Nam reacted better  with post-infection ferret antisera raised against the  A/duck/Vietnam/NCVD1584/2012 CVV. Clade 2.3.2.1g HA sequences from  viruses circulating in multiple islands of the Republic of Indonesia in the previous  reporting period were analysed. Currently, there is no CVV proposed for  this clade. These viruses accumulated many amino acid substitutions when  compared to the sequences of CVVs of closely related clades previously classified  as clade 2.3.2.1c (...). No antigenic data were available from recently detected  viruses and will require further monitoring. Clade 2.3.4.4b viruses were  detected in birds in many countries, areas and territories in Africa, Antarctica, Asia, Europe, North America and South America. A(H5N1) viruses have  continued to circulate in birds in most regions; A(H5N6) viruses have been  detected in Eastern Asia; A(H5N5) viruses have been detected in Europe and North America; and A(H5N9) viruses were detected in poultry in the USA.  Infections in wild and captive mammals have continued to be reported, as well as  the ongoing outbreak in dairy cattle with subsequent spread to poultry, peri- domestic birds, and mammals in the USA. During this period, 2 additional  spillovers from wild birds to dairy cattle were reported in the USA. Since March  2024, the ongoing dairy cattle outbreak has spread to over 970 herds in 17  states. The majority of HAs from the characterized 2.3.4.4b viruses had less than  10 amino acid substitutions compared to the 2.3.4.4b CVVs, and most tested  viruses from dairy cattle reacted well to at least 1 of the post-infection ferret  antisera raised against the 2.3.4.4b CVVs. Ongoing circulation of virus in wild  birds in North America resulted in numerous outbreaks in commercial and  backyard poultry in the USA and Canada. Viruses tested reacted well with post- infection ferret antisera raised against at least 1 of the 2.3.4.4b CVVs (Table 2).  A(H5N6) and A(H5N1) viruses identified in China had only 3-7 HA amino  acid substitutions compared to 2.3.4.4b CVVs. Most viruses tested reacted well  with post-infection ferret antisera raised to viruses related to the current CVVs,  albeit with some A(H5N6) viruses showing reduced reactivity. Viruses detected in  wild birds and/or poultry in multiple countries in Europe and Asia reacted well with  post-infection ferret antisera raised to at least 1 of the available CVVs.  Several viruses identified in poultry in Egypt showed reduced reactivity to post- infection antisera raised to CVVs and require further monitoring. Clade 2.3.4.4h A(H5N6) viruses were detected in poultry in Fujian and Guangdong provinces of China. Detections of 2.3.4.4h viruses have been infrequent over recent years  but have been noted in the last 2 reporting periods, including 2 human infections  reported in 2024. The A(H5N6) viruses had accumulated up to 14 HA amino acid  substitutions relative to available CVVs and reacted poorly to post-infection ferret  antiserum raised against a surrogate of the A/Guangdong/18SF020/2018 CVV.  Similarly, 1 of the 2 human cases detected in 2024 reacted poorly to post- infection ferret antiserum raised against the A/Guangdong/18SF020/2018 CVV, the other reacted well, likely due to a single HA amino acid substitution (...). 


Influenza A(H5) candidate vaccine viruses 

Based on current genetic, antigenic and epidemiologic data, new CVVs that are antigenically like A/Victoria/149/2024 (clade 2.3.2.1a) and A/Fujian/2/2024  (clade 2.3.4.4h) are proposed. The available and pending A(H5) CVVs are listed in  Table 5. 


Influenza A(H9N2) 

Influenza A(H9N2) viruses are enzootic in poultry in many parts of Africa, Asia and the Middle East with the majority of viruses belonging to either the B  or G HA lineage.{6} Since the late 1990s, when the first human infection was  identified, sporadic detections of A(H9N2) viruses in humans and pigs have been  reported, with associated mild disease in most human cases and no evidence for  sustained human-to-human transmission. 


Influenza A(H9N2) activity from 24 September 2024 to 24 February 2025 

Sixteen A(H9N2) human infections have been identified in China, 1 of which  had an illness onset date in the previous reporting period. Twelve of the infections  were in individuals under the aged <10 years and all infected individuals  recovered. 


Genetic and antigenic characteristics of influenza A(H9N2) viruses 

The HAs of the 11 human viruses that were sequenced belonged to the B4.7  clade. Ten of these viruses had HAs that clustered phylogenetically, having  at most 10 amino acid substitutions relative to A/Anhui-Tianjiaan/11086/2022,  from which a CVV is being developed. The other virus had a genetically distinct HA  that was more similar to the A/Anhui-Lujiang/39/2018 CVV with 12 amino  acid substitutions relative to this CVV. All of the human viruses tested antigenically  reacted well to post-infection ferret antisera raised to A/Anhui-Tianjiaan/11086/2022 or A/Anhui-Lujiang/39/2018. A(H9N2) viruses from birds  belonged to the following clades: Clade B4.5 viruses were detected in Republic of  Indonesia, although from samples collected in the previous period, and from Viet  Nam. The HAs of the viruses from Republic of Indonesia had at least 19 amino  acid substitutions compared to available CVVs. No viruses were available for  antigenic characterization. The viruses from Viet Nam, despite having  accumulated over 20 HA amino acid substitutions, reacted well to post-infection  ferret antiserum raised against the A/chicken/Hong Kong/G9/1997 CVV. Clade  B4.7 viruses continued to predominate in poultry in China, and similar viruses  were detected in poultry in Cambodia, Lao People’s Democratic Republic, and Viet  Nam. Viruses from this clade continued to diversify genetically but reacted well  with post-infection ferret antiserum raised against the A/Anhui-Lujiang/39/2018- like CVV. Clade G5.6 viruses were detected in poultry in Egypt. Despite the  accumulation of up to 24 HA amino acid substitutions relative to the  A/Oman/2747/2019 CVV, post-infection ferret antiserum raised against this CVV  reacted well with the viruses from Egypt. Clade G5.7 viruses were detected in  Bangladesh and in a sample from India collected in the previous reporting period.  The HAs of recent viruses fell into phylogenetically distinct clusters differentiated  by country. The recent viruses from Bangladesh reacted well with post-infection  ferret antisera raised against the A/Oman/2747/2019 and  A/Bangladesh/0994/2011 CVVs. The virus from India was not available for  characterisation. 


Influenza A(H9N2) candidate vaccine viruses 

Based on the available antigenic, genetic and epidemiologic data, no new  CVVs are proposed. The available and pending A(H9N2) CVVs are listed in Table  6. 


Influenza A(H10) 

A(H10) viruses are frequently detected in birds in many regions of the world  and are considered endemic in poultry in China, with rare human infections  reported. Prior to this reporting period, 3 A(H10N3), 1 A(H10N5), 4 A(H10N7) and  3 A(H10N8) human infections were detected in China and A(H10N7) viruses  were detected in individuals with conjunctivitis or mild upper respiratory tract  symptoms in Australia (n=2) and Egypt (n=2). 


Influenza A(H10) activity from  24 September 2024  to 24 February 2025 

An A(H10N3) virus infection was identified in China in an adult with severe  illness who recovered. Antigenic and genetic characteristics  of influenza A(H10N3)  viruses The HA of the human virus was similar to those of the  A(H10N3) viruses previously detected in humans in China, but distinct from that  of a previously identified A(H10N5) human virus in China, in 2024. The internal  gene segments of the A(H10N3) virus were most similar to those of A(H9N2)  viruses circulating in chickens in China and its HA had 13 amino acid substitutions  compared to A/Jiangsu/428/2021, from which a CVV has been proposed. Antigenic data are pending. A(H10N7) viruses have been identified in poultry in Cambodia. The HAs of these viruses were most closely related to sequences of  A(H10) viruses detected in wild birds in East Asia, Southeast Asia and North  America and related to A(H10N3) viruses detected in humans in China. However,  the internal genes of the A(H10N7) viruses detected in Cambodia were unrelated  to the internal genes of the A(H10N3) viruses from humans in China. 


Influenza  A(H10N3) candidate vaccine viruses 

Based on the available genetic and epidemiologic data, no new CVVs are proposed. The pending A(H10N3) CVV is listed in Table 7. 


Influenza A(H1)v{7} 

Influenza A(H1) viruses are enzootic in swine populations in most regions  of the world. The genetic and antigenic characteristics of the viruses circulating in  different regions are diverse. Viruses isolated from human infections with swine  influenza A(H1) viruses are designated as A(H1) variant ((H1)v) viruses and have  been previously detected in the Americas, Asia and Europe. 


Influenza A(H1)v  activity from 24 September 2024  to 24 February 2025 

Multiple clades of A(H1) viruses were detected in swine populations globally  with 1 A(H1N1)v virus infection detected in China and 1 A(H1N2)v virus infection  detected in the USA (...). Genetic and antigenic characteristics of influenza A(H1)v  viruses The virus from the A(H1N2)v case detected in the USA belonged  to clade 1B.2.1 which is known to circulate in swine in the USA. The virus from the  case detected in China was a clade 1C.2.3 virus. Antigenic analysis of the  viruses from these cases were not performed because viruses could not be  recovered from the samples. Influenza A(H1)v candidate vaccine viruses Based on  the available antigenic, genetic and epidemiologic data, no new A(H1)v CVVs  are proposed. The available and pending A(H1)v CVVs are listed in Table 9.


Influenza A(H3N2)v 

Influenza A(H3N2) viruses with diverse genetic and antigenic characteristics are enzootic in swine populations in most regions of the world.  Human infections with influenza A(H3N2)v viruses originating from swine have  been previously documented in Asia, Australia, Europe and the Americas.  


Influenza A(H3N2)v activity from 24 September 2024 to 24 February 2025

A(H3N2) viruses were detected in swine in Canada and the USA (...). No  cases of infection with A(H3N2) v viruses were detected in this reporting period. 


Acknowledgements 

Acknowledgement goes to the WHO Global Influenza Surveillance and Response System (GISRS) which provides the mechanism for detection and monitoring of zoonotic influenza viruses. We thank the National Influenza Centres (NICs) of GISRS who contributed information, clinical specimens and viruses, and associated data; WHO collaborating centres of GISRS for their in-depth characterization and analysis of viruses and preparation of CVVs; and the U.S. Centers for Disease Control and Prevention, the U.S. Food and Drug Administration/Center for Biologics Evaluation and Research, WHO Essential Regulatory Laboratories of GISRS and WHO H5 Reference Laboratories for their complementary analyses and preparation of CVVs. We acknowledge the WOAH/FAO Network of Expertise on Animal Influenza (OFFLU) laboratories for their in-depth characterization and comprehensive analysis of viruses and other national institutions for contributing information and viruses. We also acknowledge the GISAID Global Data Science Initiative for the EpiFluTM database, and other sequence databases which were used to share gene sequences and associated information. 

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{1} For information relevant to other notifiable influenza virus infections in animals refer to https://wahis.woah.org/#/home 

{2} See https://www.who.int/teams/global-influenza-programme/vaccines/who-recommendations/zoonotic-influenza-viruses-and-candidate-vaccine-viruses 3 See https://onlinelibrary.wiley.com/doi/10.1111/irv.12324 4 See https://pubmed.ncbi.nlm.nih.gov/39829835/ 

{5} See No. 43, 2024, pp.–621-640.

{6} See https://wwwnc.cdc.gov/eid/article/30/8/23-1176_article 

{7} Standardization of terminology for the influenza virus variants infecting humans: Update https://cdn.who.int/media/docs/default-source/influenza/global-influenza-surveillance-and-response-system/nomenclature/standardization_of_terminology_influenza_virus_variants_update.pdf?sfvrsn=d201f1d5_6

Source: World Health Organization, https://iris.who.int/bitstream/handle/10665/380900/WER10013-14-eng-fre.pdf

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Tuesday, January 28, 2025

Avian #influenza #risk of #upsurge and regional spread through increased #poultry #trade before and during #Lunar New Year #festivities in #Asia

FAO calls for increased vigilance and preparedness for avian influenza (AI) during the traditional New Year festivities that will take place across Asia on the week of 27 January 2025.

In the past year, outbreaks of AI have continued to be reported in domestic poultry, wild birds and mammals in Asia. Several AI virus subtypes including H5N1, H5N2, H5N3, H5N5, H5N6, H5N8, H7N3, H7N6, H7N8, H7N9, H10N5, and H3N2 are currently well-established in both wild and domestic bird populations in the region. In addition, subtype H5N1 subclade 2.3.4.4b continues to circulate in both wild and domestic birds worldwide.

Highly pathogenic avian influenza (HPAI) can lead to heavy losses for the poultry industry, in particular to the livelihoods of vulnerable small-scale producers. Poultry trade and related activities play a key role in AI spread and amplification in domestic bird populations, including the trade of infected live poultry and their products, handling or slaughtering infected poultry, and limited biosecurity along the poultry value chain. Before and during New Year festivities, the risk is further exacerbated by high demand for poultry meat and products, triggering increased and intensified poultry trade and movements as well as visits to live poultry markets.

In addition, a rise in mammalian species infected with HPAI has been recorded globally including outbreaks in farmed mink in Europe, marine mammals in the Americas, cats in the Republic of Korea, and more recently in red foxes and raccoon dogs in Japan, and in captive wild felids in Viet Nam. Notably in 2024, HPAI H5N1 has been found in raw milk of dairy cows – the animals experienced clinical signs including decreased milk production, thickened colostrum-like milk, reduced food intake, lethargy, fever, loose manure and dehydration.

Importantly, AI virus subtypes have demonstrated their zoonotic potential, i.e. the ability to transmit between birds and humans. During 2024, in the Region of Asia and the Pacific, human cases of influenza A(H5N1) were detected in Australia, Cambodia, and Viet Nam. HPAI A(H5N6) was also reported in China. Other subtypes have also been associated with zoonotic transmission in Asia in the past year, including influenza, A(H3N8), and A(H9N2).

Most of these cases reported exposure through close contact with infected live poultry. While human infections with AI viruses remain sporadic events and do not currently spread easily from person to person, they warrant attention since symptoms observed in humans range from asymptomatic to severe and can be fatal.


INCREASED AVIAN INFLUENZA RISK

There is an increased risk of AI spread in Asia due to intensified in-country travel around Lunar New Year (January-February 2025), specifically considering the following:

-- millions of people are expected to travel for the New Year (starting late January 2025);

-- vast majority of traffic will be within countries of the Asian region, but also to and from Asia;

-- poultry trade is increasing to serve the high demand for poultry meat and other products consumed during these festivities;

-- travel and trade increase the risk of spreading AI, since the virus can be transmitted via contact with infected animals as well as contaminated clothing, vehicles and other equipment.


RECOMMENDED ACTIONS

In light of the elevated risk, FAO is calling on all Chief Veterinary Officers (CVOs) in Asia to increase AI prevention and preparedness activities to reduce the likelihood of poultry outbreaks and subsequent impacts on livelihoods, economies, and human infections.

Specifically, FAO recommends countries to:

-- Enhance controls at national borders and along traffic routes based on risk analyses to minimize the risk of introduction of potentially infected live poultry and poultry products.

-- Promote improved biosecurity measures along the value chain, including at farms, live bird markets, slaughter points, etc. to limit further spread of the disease and mitigate the risk of human exposure.

-- Implement measures for early detection, timely reporting and rapid containment of infection, as delays can lead to rapid spread. In addition, the adoption of policies that encourage disease reporting, such as providing adequate compensation following animal culling, can help mitigate these threats.

-- On infected premises (e.g. farms or live bird markets including associated vehicles), conduct appropriate cleaning and disinfection and take action on carcasses, slurry and faecal waste to ensure they do not pose a risk for further transmission and spread of virus. Where possible, use the period immediately following the Lunar New Year festivities for short closures of live bird markets for decontamination after all birds have been sold and processed.

-- Upon detection of outbreaks, timely alert neighbouring countries as well as international organizations, including the World Organisation for Animal Health (WOAH). This includes rapid sharing of virus sequences with relevant partners to ensure appropriate actions are taken by countries in the region (e.g. ensuring the use of adapted vaccines in countries that implement vaccination programmes against AI). The OFFLU Avian Influenza Vaccine Matching (AIM) for poultry vaccines is available for guidance.

-- Implement surveillance schemes that support the detection of HPAI viruses in both domestic and wild birds. Provide mechanisms for reporting sick or dead birds (hotlines, collection points) and raise awareness about the importance of reporting. Farmers, hunters, or rangers should be encouraged to report to veterinary authorities once they see unusual clinical signs in birds including: sudden increase in mortalities; swelling of the head, eyelids, comb, wattles, and hocks; purple discoloration of the wattles, comb, and legs; gasping for air (difficulty breathing); coughing, sneezing, and/or nasal discharge (runny nose); stumbling or falling; or ruffled feathers or neurological disease in water birds.

-- Expand surveillance to relevant mammals, for better early detection of HPAI viruses, and to understand their role in the epidemiology, spread and transmission of avian influenza, including in dairy cattle. FAO Recommendations for the surveillance of influenza A(H5N1) in cattle and A list of mammalian species affected by H5Nx are available for guidance.

-- Ensure laboratories have adequate capacities to diagnose circulating H5Nx HPAI viruses and deploy point-of-need rapid tests as appropriate.

-- Implement targeted sampling of animals with a higher likelihood of detecting the virus. Targeting sick or freshly dead birds as well as sampling their environment will increase the probability of detecting AI viruses.

-- Shift to active surveillance, differential diagnosis, and increased virological screening. Active surveillance in key hotspots of the poultry value chain such as live bird markets allows for early detection of AI virus incursion/amplification.

-- Collaborate closely with forestry/environment sector and wetland, or bird reserve management authorities in contact with wild bird populations to foster information-sharing and joint AI surveillance and prevention activities well ahead of the potential introduction or spread of the virus.

-- Facilitate early reporting and response by consulting closely with the private sector (i.e. producers, traders and related businesses). Preparing and sharing communication materials prior to AI virus introduction will help minimize misunderstandings and rumours.

-- Reinforce awareness campaigns. High level of awareness should be maintained among poultry keepers, the general population, traders, market workers, hunters, and any other relevant stakeholder about AI, precautionary and personal protection measures as well as reporting and collection mechanisms for sick or dead birds.

-- Action against wild birds, particularly indiscriminate hunting or disturbances of habitat, should not be undertaken. Guidance is available to respond to HPAI in wild birds.


WHAT FAO IS DOING

-- Tracking disease rumours in Asia and the Pacific and sharing relevant information with stakeholders in the region on a bi-weekly basis. Please see FAO ECTAD event-based surveillance in Asia and the Pacific bi-weekly update for more information.

-- Conducting consultations with AI experts in Asia and the Pacific to identify innovative approaches to respond to emerging AI threats. Published consultation reports are available at this link.

-- Conducting public health assessments jointly with Tripartite partners (FAO/WHO/WOAH) of recent influenza A(H5) virus events in animals and people.

-- Monitoring and assessing the evolving disease situation. To share updates on your country's situation, please contact FAO at FAO-GLEWS@fao.org.

-- Liaising with FAO/WOAH Reference Laboratories and partner organizations to assess virus characteristics and provide laboratory protocols for detection.

-- Raising awareness about important epidemiological and virological findings and their implications.

-- Providing recommendations for affected countries and those at risk addressing preparedness, prevention and disease control.

-- Providing support for risk assessment and mapping to identify hot spots for risk mitigation and the implementation of risk-based surveillance.

-- Offering support in the provision of diagnostic reagents and personal protective equipment, provided certain conditions are met (contact: EMPRES-Lab-Unit@fao.org).

-- Offering assistance to national authorities for shipment of samples as well as virus sub-typing and sequencing, provided certain conditions are met (contact: EMPRES-Shipping-Service@fao.org).

Source: Food and Agriculture Organization, https://www.fao.org/animal-health/situation-updates/global-aiv-with-zoonotic-potential#alert

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Friday, January 24, 2025

Characterization of novel highly pathogenic avian #influenza A(#H5N6) clade 2.3.4.4b virus in wild #birds, East #China, 2024

{Excerpt}

Dear Editor,

The highly pathogenic avian influenza viruses (HPAIVs) are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health. Wild birds have been recognized as the primary reservoirs for influenza A virus, and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus (Lycett et al., 2019). Since it was first discovered in 1959, the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds, poultry and sporadic human and other mammalian infections (Lycett et al., 2019). Due to the reassortant events of diverse strains facilitated by migratory waterfowl, the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase (NA) gene from other low pathogenicity avian influenza viruses (LPAIVs) emerged in 2014 and gradually became the dominant sub-clade (Lee et al., 2017). The genetic diversity of clade 2.3.4.4 of H5Nx hemagglutinin (HA) has further evolved into eight subclades (2.3.4.4a to 2.3.4.4h) according to a unified nomenclature (Graziosi et al., 2024). H5N6 of clades 2.3.4.4d-h were predominantly identified in China from 2014 to early 2020 until the occurrence of a novel H5N6 derived the clade 2.3.4.4b HA gene of H5N8 in December 2020 (Gu et al., 2022). Subsequently, the preponderant clade of the H5N6 subtype HPAIV in China switched into 2.3.4.4b. Recently, novel H5N6 HPAIVs containing HA gene from clade 2.3.4.4b H5N1 virus entered R. O. Korea, with disease outbreaks in poultry and wild bird mortality events (Cho et al., 2024; Heo et al., 2024).

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000021?via%3Dihub

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Friday, December 20, 2024

#Phylogenetic and #Pathogenic #Analysis of #H5N1 and #H5N6 High Pathogenicity Avian #Influenza Virus Isolated from #Poultry Farms (Layer and Broiler Chickens) in #Japan in the 2023/2024 Season

Abstract

During the 2023–2024 winter, 11 high pathogenicity avian influenza (HPAI) outbreaks caused by clade 2.3.4.4b H5N1 and H5N6 HPAI viruses were confirmed in Japanese domestic poultry among 10 prefectures (n = 10 and 1, respectively). In this study, we aimed to genetically and pathologically characterize these viruses. Phylogenetic analysis revealed that H5N1 viruses were classified into the G2d-0 genotype, whereas the H5N6 virus was a novel genotype in Japan, designated as G2c-12. The G2c-12 virus shared PB2, PB1, PA, HA, and M genes with previous G2c viruses, but had NP and NS genes originating from avian influenza viruses in wild birds abroad. The N6 NA gene was derived from an H5N6 HPAI virus that was different from the viruses responsible for the outbreaks in Japan in 2016–2017 and 2017–2018. Experimental infections in chickens infected with H5N1(G2d-0) and H5N6(G2c-12) HPAI viruses showed no significant differences in the 50% chicken lethal dose, mean death time, or virus shedding from the trachea and cloaca, or in the histopathological findings. Different genotypes of the viruses worldwide, their introduction into the country, and their stable lethality in chickens may have triggered the four consecutive seasons of HPAI outbreaks in Japan.

Source: Viruses, https://www.mdpi.com/1999-4915/16/12/1956

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