#ah5n1 — Public Fediverse posts

Establishing #methods to #monitor #H5N1 #influenza virus in dairy #cattle #milk

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.12.04.24318491v1

Abstract
Highly Pathogenic Avian Influenza strain H5N1 has caused a multi-state outbreak among US dairy cattle, spreading across 15 states and infecting hundreds of herds since its onset. We rapidly developed and optimized PCR-based detection assays and sequencing protocols to support H5N1 molecular surveillance. Using 214 retail milk from 20 states for methods development, we found that H5N1 concentrations by digital PCR strongly correlated with qPCR cycle threshold (Ct) values, with dPCR exhibiting greater sensitivity. We also found that metagenomic sequencing after hybrid selection was best for higher concentration samples while amplicon sequencing performs best for lower concentrations. By establishing these methods, we were able to support the creation of a statewide surveillance program to test bulk milk samples monthly from all cattle dairy farms within Massachusetts, which remain negative to date. The methods, workflow, and recommendations described here provide a framework for others aiming to conduct H5N1 surveillance efforts.

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#aH5n1 #abstract #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #dairyProducts #diagnosticTests #foodSafety #h5n1 #health #massachusetts #news #research #USA

Structural Convergence and Water-Mediated Substrate Mimicry Enable Broad #Neuraminidase #Inhibition by #Human #Antibodies

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.27.625426v1?rss=1

Abstract
Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedness and effective countermeasures, including monoclonal antibodies (mAbs). Here, we characterize human mAbs that target the highly conserved catalytic site of viral neuraminidase (NA), termed NCS mAbs, and the molecular basis of their broad specificity. Cross-reactive NA-specific B cells were isolated by using stabilized NA probes of non-circulating subtypes. We found that NCS mAbs recognized multiple NAs of influenza A as well as influenza B NAs and conferred prophylactic protections in mice against H1N1, H5N1, and influenza B viruses. Cryo-electron microscopy structures of two NCS mAbs revealed that they rely on structural mimicry of sialic acid, the substrate of NA, by coordinating not only amino acid side chains but also water molecules, enabling inhibition of NA activity across multiple influenza A and B viruses, including avian influenza H5N1 clade 2.3.4.4b viruses. Our results provide a molecular basis for the broad reactivity and inhibitory activity of NCS mAbs targeting the catalytic site of NA through substrate mimicry.

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#aH1n1 #aH5n1 #abstract #avianInfluenza #AVIANINFLUENZA #birdFlu #h5n1 #health #influenzaB #monoclonalAntibodies #news #research #SEASONALINFLUENZA

#Influenza A(#H5N1) shedding in #air corresponds to #transmissibility in #mammals

Source: Nature Microbiology, https://www.nature.com/articles/s41564-024-01885-6

Abstract
An increase in spillover events of highly pathogenic avian influenza A(H5N1) viruses to mammals suggests selection of viruses that transmit well in mammals. Here we use air-sampling devices to continuously sample infectious influenza viruses expelled by experimentally infected ferrets. The resulting quantitative virus shedding kinetics data resembled ferret-to-ferret transmission studies and indicated that the absence of transmission observed for earlier A(H5N1) viruses was due to a lack of infectious virus shedding in the air, rather than the absence of necessary mammalian adaptation mutations. Whereas infectious human A(H1N1pdm) virus was efficiently shed in the air, infectious 2005 zoonotic and 2024 bovine A(H5N1) viruses were not detected in the air. By contrast, shedding of infectious virus was observed for 1 out of 4 ferrets infected with a 2022 European polecat A(H5N1) virus and a 2024 A(H5N1) virus isolated from a dairy farm worker.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #pathogensAirborneTransmission #research

#Influenza A(#H5N1) shedding in #air corresponds to #transmissibility in #mammals

Source: Nature Microbiology, https://www.nature.com/articles/s41564-024-01885-6

Abstract
An increase in spillover events of highly pathogenic avian influenza A(H5N1) viruses to mammals suggests selection of viruses that transmit well in mammals. Here we use air-sampling devices to continuously sample infectious influenza viruses expelled by experimentally infected ferrets. The resulting quantitative virus shedding kinetics data resembled ferret-to-ferret transmission studies and indicated that the absence of transmission observed for earlier A(H5N1) viruses was due to a lack of infectious virus shedding in the air, rather than the absence of necessary mammalian adaptation mutations. Whereas infectious human A(H1N1pdm) virus was efficiently shed in the air, infectious 2005 zoonotic and 2024 bovine A(H5N1) viruses were not detected in the air. By contrast, shedding of infectious virus was observed for 1 out of 4 ferrets infected with a 2022 European polecat A(H5N1) virus and a 2024 A(H5N1) virus isolated from a dairy farm worker.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #pathogensAirborneTransmission #research

#Influenza A(#H5N1) shedding in #air corresponds to #transmissibility in #mammals

Source: Nature Microbiology, https://www.nature.com/articles/s41564-024-01885-6

Abstract
An increase in spillover events of highly pathogenic avian influenza A(H5N1) viruses to mammals suggests selection of viruses that transmit well in mammals. Here we use air-sampling devices to continuously sample infectious influenza viruses expelled by experimentally infected ferrets. The resulting quantitative virus shedding kinetics data resembled ferret-to-ferret transmission studies and indicated that the absence of transmission observed for earlier A(H5N1) viruses was due to a lack of infectious virus shedding in the air, rather than the absence of necessary mammalian adaptation mutations. Whereas infectious human A(H1N1pdm) virus was efficiently shed in the air, infectious 2005 zoonotic and 2024 bovine A(H5N1) viruses were not detected in the air. By contrast, shedding of infectious virus was observed for 1 out of 4 ferrets infected with a 2022 European polecat A(H5N1) virus and a 2024 A(H5N1) virus isolated from a dairy farm worker.

____

#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #pathogensAirborneTransmission #research

#Influenza A(#H5N1) shedding in #air corresponds to #transmissibility in #mammals

Source: Nature Microbiology, https://www.nature.com/articles/s41564-024-01885-6

Abstract
An increase in spillover events of highly pathogenic avian influenza A(H5N1) viruses to mammals suggests selection of viruses that transmit well in mammals. Here we use air-sampling devices to continuously sample infectious influenza viruses expelled by experimentally infected ferrets. The resulting quantitative virus shedding kinetics data resembled ferret-to-ferret transmission studies and indicated that the absence of transmission observed for earlier A(H5N1) viruses was due to a lack of infectious virus shedding in the air, rather than the absence of necessary mammalian adaptation mutations. Whereas infectious human A(H1N1pdm) virus was efficiently shed in the air, infectious 2005 zoonotic and 2024 bovine A(H5N1) viruses were not detected in the air. By contrast, shedding of infectious virus was observed for 1 out of 4 ferrets infected with a 2022 European polecat A(H5N1) virus and a 2024 A(H5N1) virus isolated from a dairy farm worker.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #pathogensAirborneTransmission #research

Polygenic #Determinants of #H5N1 #Adaptation to Bovine Cells

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.29.626120v1

Abstract
H5N1 avian influenza virus (lineage 2.3.4.4b, B3.13 genotype) has caused, unexpectedly, a large outbreak in dairy cattle in North America. It is critical to ascertain how this virus has specifically adapted to bovine cells and the molecular determinants of this process. Here, we focused on the contribution of the viral internal genomic segments of H5N1 B3.13 to bovine cells adaptation. We generated 45 reassortant viruses harbouring the haemagglutinin and neuraminidase from A/Puerto Rico/8/1934 and internal gene constellations from several influenza A viruses (IAV) or carrying segment swaps between distinct H5N1 strains. The recombinant B3.13 viruses displayed faster replication kinetics in bovine cells compared to other IAV. Importantly, multiple genomic segments of B3.13 viruses contribute to their faster replicative fitness. Further, recombinants with the B3.13 internal genes were less susceptible than ancestral 2.3.4.4b strain to the bovine IFN response. However, bovine (and human) MX1, a key restriction factor for avian IAV, restricted both ancestral 2.3.4.4b and B3.13 recombinant viruses. Interestingly, the latter escape restriction from human BTN3A3. Finally, recombinant B3.13 was virulent in mice unlike the ancestor 2.3.4.4b recombinant virus. Our results highlight the polygenic nature of influenza host range as multiple internal genes of B3.13 contribute to bovine adaptation.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #news #research #viralPathogenesis

#China, #HK: #Exercise “Amazonite” enhances #Government’s #response to #human case of avian #influenza (with photos/video)

Source: Centre for Health Protection, https://www.info.gov.hk/gia/general/202411/27/P2024112700515.htm?fontSize=1

The Centre for Health Protection (CHP) of the Department of Health (DH), in collaboration with relevant government departments, today (November 27) conducted a public health exercise, code-named "Amazonite", to enhance its response capabilities in dealing with a human case of avian influenza infection, and to strengthen the execution and co-ordination abilities of the DH and relevant departments in response to a human case of avian influenza, in order to enhance awareness among stakeholders on the handling of public health emergencies.

The exercise consisted of two parts. The ground movement exercise today was held at the Cheung Sha Wan Temporary Wholesale Poultry Market. Under the exercise simulation, the CHP had received a notification from the Hospital Authority (HA) about a woman with avian influenza A (H5N1) virus infection, and commenced epidemiological investigations immediately. The investigations revealed that the patient was a chicken stallholder at a wet market. The CHP co-ordinated with relevant departments to conduct on-site investigations and risk assessment, and implement control measures at the patient’s residential building, the market where she worked, the wholesale poultry market, and related chicken farms. The ground movement exercise tested the capability of the CHP and relevant departments to carry out investigation and control measures, which included contact tracing and prescription of prophylactic antiviral therapy; chicken, environmental and sewage sampling; culling of chickens and disinfecting environmental. Approximately 30 personnel from four government departments participated in this ground movement exercise, along with over 30 experts from the Mainland, Macao and Singapore health authorities, who were invited to attend as observers.

The expert observers also attended the exercise briefing held at the CHP in the morning before the ground movement exercise, and visited the Lai Wan Market in the afternoon after the ground movement exercise to learn about the design features of new-style poultry stalls in the market.

The first part of the exercise, conducted on November 7, was a table-top exercise in which four relevant government departments and the HA discussed and co-ordinated the response measures required in a simulated scenario when a local human case of avian influenza A (H5N1) was reported in Hong Kong.

“This exercise provided a valuable opportunity for relevant government departments and the HA to test the response capabilities of stakeholders in the handling of a human case of avian influenza. The DH has held 30 similar exercises in the past, simulating the situation with cases such as measles, plague, Middle East Respiratory Syndrome and Ebola virus disease to enhance the community and healthcare personnel’s awareness of possible epidemics, and keep them alert and prepared,” the spokesman for the CHP said.

Avian influenza is caused by influenza A viruses that mainly affect birds and poultry, such as chickens or ducks. Some avian influenza viruses can infect and spread to other animals, such as mammals, as well. Humans mainly become infected with avian influenza virus through direct contact with infected animals or contaminated environments.

“According to the World Health Organization (WHO) and health authorities outside Hong Kong, as of November 2024, more than 900 human cases of avian influenza A (H5N1) have been reported worldwide. So far this year, an increasing number of related cases were reported globally than previous years, with most of them reported from the United States. Locally, avian influenza is one of the statutory notifiable infectious diseases in Hong Kong. Since 1997, a total of 22 human cases of avian influenza A (H5N1) have been recorded in Hong Kong, among which seven had died. The most recent case was recorded in 2012. Although there is no evidence of genetic mutations in the avian influenza A (H5N1) virus that are associated with increased infectivity among people, the WHO has indicated that the global mortality rate of human cases of avian influenza A (H5N1) in the past 20 years has exceeded 50 per cent. We shall stay vigilant and get prepared to prevent and combat the disease,” the spokesman said.

For more information on avian influenza, the public may visit the CHP’s thematic page on avian influenza.

Ends/Wednesday, November 27, 2024
Issued at HKT 19:45

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#aH5n1 #avianInfluenza #AVIANINFLUENZA #birdFlu #china #h5n1 #health #HKPRCSAR #news #pandemicPreparedness #updates

13th #Meeting of #WHO Expert Working #Group on #Surveillance of #Antiviral Susceptibility of #Influenza Viruses for WHO #GISRS

Source: World Health Organization, Weekly Epidemiological Record: https://www.who.int/publications/journals/weekly-epidemiological-record

{Excerpt, edited}

Executive summary

The WHO Expert Working Group on Surveillance of Influenza Antiviral Susceptibility (AVWG) supports the WHO Global Influenza Surveillance and Response System (GISRS) by providing practical guidance for monitoring the antiviral susceptibility of seasonal and emerging influenza viruses The 13th WHO AVWG meeting was held in hybrid format (faceto-face and virtually) on 13–14 June 2024 in Lyon, France.

Update on susceptibility of seasonal influenza viruses to approved antiviral agents

Between May 2023 and May 2024, WHO collaborating centres (CCs) and participating national influenza centres (NICs) reported that seasonal influenza activity in various regions had resumed to levels before the coronavirus disease 2019 (COVID-19) pandemic. Co-circulation of A(H1N1)pdm09, A(H3N2) and influenza B/Victoria lineage viruses was detected in most regions. Overall, influenza A and B viruses with reduced inhibition (RI) or highly reduced inhibition (HRI) to neuraminidase (NA) inhibitors (NAIs) were detected at low frequency. The most frequently identified substitution associated with RI or HRI by NAIs was NA-H275Y in A(H1N1)pdm09 viruses, which was detected at <2%. Double amino acid substitutions (NA-I223V+ NA-S247N) in A(H1N1)pdm09 viruses (referred to as dual mutant viruses) that resulted in RI by oseltamivir were first detected in May 2023 and spread rapidly to several regions of the world.{1,2} Influenza A and B viruses with amino acid substitutions in the polymerase acidic (PA) protein associated with reduced susceptibility to endonuclease inhibitor (baloxavir) were detected at low frequency. The PA-I38X (including I38T, I38N, I38M and I38V) amino acid substitution being the most frequently reported, but the overall detection frequency has remained low (<2%).

Update on susceptibility of zoonotic and animal influenza viruses to approved antiviral agents

From May 2023 to May 2024, clade 2.3.4.4b A(H5N1) highly pathogenic avian influenza (HPAI) viruses continued to be detected in various regions of the world. Since early 2024, there has been an outbreak of clade 2.3.4.4b A(H5N1) genotype B3.13 viruses in dairy cattle in several states in the United States of America, resulting in sporadic zoonotic infections in humans. In addition, human infection with clade 2.3.2.1c A(H5N1) HPAI has been reported in Cambodia and Viet Nam. WHO CCs, participating NICs and WHO H5 reference laboratories reported antiviral susceptibility testing of A(H5N1) HPAI, low pathogenic avian influenza (LPAI) of various subtypes and swine influenza viruses. Of the clade 2.3.4.4b A(H5N1) HPAI viruses, the NA-T438I substitution, which confers RI by zanamivir and peramivir, was detected at <2% frequency. NA-H275Y, NA-N295S and NA-N295S+NA-T438N associated with RI or HRI by NAIs were also detected among A(H5N1) viruses. NA-T438I has been detected in A(H5N1) viruses isolated from dairy cattle. PA-I38T, PA-A37T and PA-I38M, associated with reduced susceptibility to baloxavir, were detected in A(H5N1) viruses. Most A(H5N1) HPAI viruses remain susceptible to M2 ion channel blockers. Among LPAI, NA-H274Y with HRI by oseltamivir was detected in one A(H8N4) isolate. PA-E199G with reduced susceptibility to baloxavir was detected in one A(H9N2) virus. Overall, animal or zoonotic influenza viruses with reduced susceptibility to NAIs or baloxavir were detected at very low frequencies.

Update of protocols and guidance for GISRS laboratories

Genotypic and/or phenotypic assays can be used to monitor the susceptibility of influenza viruses to NAIs and baloxavir. The WHO AVWG routinely reviews and updates information on NA{3,4} and PA{5} amino acid substitutions associated with reduced susceptibility to NAIs and baloxavir, respectively. Reference virus panels that can be used for NAI and baloxavir susceptibility testing are available for GISRS laboratories at the International Reagent Resource.{6} The WHO AVWG will develop an algorithm for NICs to decide on testing strategies (genotypic versus phenotypic) and methods according to their capacity. Guidance on phenotypic assays for NAI susceptibility testing is provided in a WHO guidance document to NICs, which was updated in 2018.{7} A new phenotypic assay has been developed for testing susceptibility to baloxavir.{8} The protocol will be posted on the WHO website. The WHO-AVWG will also update the WHO guidance document to NICs to include the new phenotypic assay for baloxavir susceptibility testing. In addition, the WHO AVWG will work with the Global Initiative on Sharing All Influenza Data{9} to facilitate identification of NA and PA substitutions in submitted sequences.

Review of external quality assessment programme (EQAP) panels

EQAP was initiated in 2007, and the antiviral panel was introduced in 2013 (panel 12) as an optional component of EQAP to evaluate the ability of NICs to identify influenza viruses with reduced susceptibility to NAIs. Genotypic testing for baloxavir susceptibility was introduced in 2020 (panel 19) for educational purpose (i.e. not scored). Results for the 2023 Global EQAP panel were reported at the 13th WHO AVWG meeting. A total of 178 laboratories participated in the 2023 EQAP; 46 (25.8%) participated in NAI susceptibility testing and 16 (9.0%) in baloxavir susceptibility testing. The results from the Global EQAP antiviral panel are used by members of the WHO AVWG to assess the training requirements of NICs.

Way forward

Two reports, on global antiviral surveillance in 2020-2023 and in 2023–2024, are being prepared for publication. The next WHO AVWG meeting is scheduled for June 2025.

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{1} Leung RC et al. Global emergence of neuraminidase inhibitor-resistant influenza A(H1N1)pdm09 viruses with I223V and S247N mutations: implications for antiviral resistance monitoring. Lancet Microbe. 2024;5(7):627–8. doi:10.1016/S26665247(24)00037-5.

{2} Patel MC et al. Multicountry spread of influenza A(H1N1)pdm09 viruses with reduced oseltamivir inhibition, May 2023-February 2024. Emerg Infect Dis. 2024;30(7):1410–5. doi:10.3201/eid3007.240480.

{3} Summary of neuraminidase (NA) amino acid substitutions associated with reduced inhibition by neuraminidase inhibitors (NAIs). Geneva: World Health Organization; 2023 (https://www.who.int/publications/m/item/summary-of-neuraminidase-(na)-amino-acid-substitutions-associated-with-reduced-inhibition-by-neuraminidase-inhibitors-(nais).

{4} Summary of neuraminidase (NA) amino acid substitutions associated with reduced inhibition by neuraminidase inhibitors (NAIs) among avian influenza viruses of Group 1 and Group 2 NAs. Geneva: World Health Organization; 2024 (https://www. who.int/publications/m/item/summary-of-neuraminidase-(na)-amino-acid-substitutions-associated-with-reduced-inhibition-by-neuraminidase-inhibitors-(nais)among-avian-influenza-viruses-of-group-1-and-group-2-nas).

{5} Summary of polymerase acidic (PA) protein amino acid substitutions analysed for their effects on baloxavir susceptibility. Geneva: World Health Organization; 2024 (https://www.who.int/publications/m/item/summary-of-polymerase-acidic-(pa)-protein-amino-acid-substitutions-analysed-for-their-effects-on-baloxavirsusceptibility).

{6} See https://www.internationalreagentresource.org.

{7} Practical guidance for national influenza centres establishing or implementing neuraminidase inhibitor susceptibility surveillance. Geneva: World Health Organization; 2024 (https://www.who.int/publications/i/item/practical-guidance-for-national-inf luenza-centres-establishing-or-implementing-neuraminidase-inhibitor-susceptibility-surveillance).

{8} Baloxavir susceptibility assessment using influenza replication inhibition neuraminidase-based assay (IRINA). Atlanta (GA): Centers for Disease Control and Prevention; 2023 (https://cdn.who.int/media/docs/default-source/influenza/avwg/ cdc-phenotypic-lp-492rev01d—baloxavir-susceptibility-assessment-using-irina. pdf?sfvrsn=f24254ac_3).

{9} See https://gisaid.org.

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#aH3n2 #aH5n1 #aH9n2 #amantadine #antivirals #AVIANINFLUENZA #baloxavir #birdFlu #drugsResistance #h1n1pdm09 #h5n1 #health #influenza #oseltamivir #science #SEASONALINFLUENZA #updates #WHO #zanamivir

Single-dose avian #influenza A(#H5N1) Clade 2.3.4.4b #hemagglutinin-Matrix-M nanoparticle #vaccine induces neutralizing responses in nonhuman #primates

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.21.624712v1?rss=1

Abstract
With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals, there is an associated increase in the risk of human-to-human transmission. In this study, we characterize recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine. Purified recombinant A/AW/SC/2021 HA trimers upon formulation with Matrix-M™ adjuvant, saponin-cholesterol-phospholipid icosahedral particles, non-covalently anchored to the vertices of the Matrix-M forming A(H5N1) HA–Matrix-M nanoparticles (H5-MNPs). In naive mice, two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induced robust antibody- and cell-mediated immune responses, including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine, a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induced geometric mean serum A(H5N1) clade 2.3.4.4b pseudovirus neutralizing titers of 1:1160 and 1:54, respectively; above the generally accepted seroconverting neutralizing titer of 1:40. Immunization with H5-MNP vaccine induced antibody responses against conserved epitopes in the A(H5N1) HA stem, vestigial esterase subdomain, and receptor binding site. This novel A(H5N1) H5-MNP IN and IM vaccine was immunogenic in rodents and NHPs as a potential A(H5N1) pandemic single-dose vaccine.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #h5n1 #health #news #pandemicPreparedness #research #vaccines

#Chicken ANP32A-independent #replication of highly pathogenic avian #influenza viruses potentially leads to #mammalian #adaptation-related amino acid substitutions in viral #PB2 and #PA proteins

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01840-24?af=R

ABSTRACT
Acidic nuclear phosphoprotein 32 family member A (ANP32A) is an important host factor that supports the efficient replication of avian influenza viruses (AIVs). To develop an antiviral strategy against Gs/Gd-lineage H5 highly pathogenic avian influenza (HPAI) viruses in chickens, we established chicken ANP32-knockout (chANP32A-KO) DF-1 cells and evaluated their antiviral efficacy through in vitro validation. The replication of all HPAI viruses tested in chANP32A-KO cells was significantly lower compared to that of wild-type DF-1 cells. However, when HPAI strains A/mountain hawk-eagle/Kumamoto/1/2007 (H5N1; MHE) and A/chicken/Aichi/2/2011 (H5N1; H5Aichi) were passed in chANP32A-KO cells, mutant viruses were generated, which exhibited comparable replication levels in both chANP32A-KO and wild-type DF-1 cells. Sequence analysis revealed that mammalian-adaptive amino acid mutations PB2_D256G and PA_T97I were present in the MHE mutant virus, and the PB2_E627K mutation was identified in the H5Aichi mutant virus. These mutations have also been reported to enhance the polymerase activity of AIVs in mammalian cells; however, the minigenome assay in the present study showed that the polymerase activity of mutant viruses in chANP32A-KO cells was not restored to levels comparable to those in wild-type DF-1 cells. These findings suggest that ANP32A-independent viral replication may induce amino acid substitutions associated with mammalian adaptation in AIVs. They also imply that the high efficiency of viral replication mediated by these amino acid mutations may not result from enhanced polymerase activity but rather involve other undefined mechanisms.

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#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #biology #birdFlu #health #research #science

Sustained #vaccine #exposure elicits more rapid, consistent, and broad #humoral immune responses to multivalent #influenza #vaccines

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.04.28.591370v2

Abstract
With the ever-present threat of pandemics, it is imperative we develop vaccine technologies eliciting broad and durable immunity to high-risk pathogens. Yet, current annual influenza vaccines, for example, fail to provide robust immunity against the 3-4 homologous strains they contain, let alone heterologous strains. Herein, we demonstrate that sustained delivery of multivalent influenza vaccines from an injectable polymer-nanoparticle (PNP) hydrogel technology induces more rapid, consistent, and potent humoral immune responses against multiple homologous viruses, as well as potent responses against heterologous viruses and potential pandemic subtypes H5N1, H7N9 and H9N2. Further, admixing PNP hydrogels with commercial influenza vaccines results in stronger hemagglutination inhibition against both heterologous and homologous viruses. We show this enhanced potency and breadth arises from higher affinity antibodies targeting both the hemagglutinin stem and head. Overall, this simple and effective sustained delivery platform for multivalent annual influenza vaccines generates durable, potent, and remarkably broad immunity to influenza.

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#aH5n1 #aH7n9 #aH9n2 #abstract #avianInfluenza #COVID19 #health #influenza #influenzaA #news #research #vaccine #vaccines

Enhanced #encephalitic #tropism of #bovine #H5N1 compared to the #Vietnam #H5N1 isolate in #mice

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.19.624162v1

Abstract
In recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection with either HPAI H5N1 isolate was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Bov342-challenged animals exhibited clinical signs consistent with central nervous system (CNS) infection, and infectious virus was detected in brain tissue. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism, with Bov342 resulting in respiratory disease as well as increased neurotropism and inflammation in the brain and nasal turbinates compared to VN1203, which predominantly induces respiratory disease.

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#research #abstract #avianInfluenza #aH5n1 #animalModels #neuroinvasion #animalHealth #health #news #birdFlu #h5n1 #AVIANINFLUENZA #dairyCow

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, Nov. 16 ’24)

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   Modulating apoptosis as a novel therapeutic strategy against Respiratory Syncytial Virus infection: insights from Rotenone.
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#aH5n1 #abstract #antivirals #covid #COVID19 #health #influenzaA #news #research #SEASONALINFLUENZA #vaccine

Interim #Guidance for #Employers to Reduce #Exposure to Novel #Influenza A (Such as #H5N1 #Birdflu) for People Working with or Exposed to Animals

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/worker-protection-ppe.html

{Summary}

This updated interim guidance identifies work tasks that may pose an increased risk of worker exposure to novel influenza A viruses associated with disease in humans and provides recommended controls for each level. Specific recommendations for these work tasks may be updated as CDC learns more during this evolving situation.

(…)

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#aH5n1 #avianInfluenza #occupationalHealth #updates #USCDC #USA

Source: WOAH, https://wahis.woah.org/#/in-review/6008

An intensive surveillance system is in place for avian influenza virus including screening at Mai Po Nature Reserve (Reserve) in Hong Kong. Among the environmental samples collected by the University of Hong Kong on 6 November 2024, a sample of wild bird fecal dropping has been confirmed to be positive for H5N1. The organization managing the reserve has stepped up cleaning and disinfection of visitor facilities. The government is closely monitoring the situation of the birds in the reserve. There are no poultry farm within 3 km of the reserve. The government has closely monitored the situation of the local poultry farms and wholesale market. Poultry farmers, pet bird shop owners and licensed holders of pet poultry and racing pigeons are reminded from time to time to ensure that proper precaution against avian influenza have been implemented.

____

https://etidioh.wordpress.com/2024/11/12/hk-influenza-a-h5n1-viruses-of-high-pathogenicity-inf-with-non-poultry-including-wild-birds-2017-immediate-notification/

#aH5n1 #avianInfluenza #HKPRCSAR #updates #wildBirds #WOAH

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/employer-provided-ppe.html

{Excerpt}

Summary

Personal protective equipment (PPE) is needed in some cases to reduce the risk of exposures, especially for workers in direct contact with animals or their secretions. Employers should provide appropriate PPE at no cost as well as training on its proper use. Employers should consider implementing controls to reduce the risk of heat related illness and injuries for workers wearing PPE in hot environments.

(…)

____

https://etidioh.wordpress.com/2024/11/08/information-for-employers-providing-ppe-to-reduce-exposure-to-novel-influenza-a/

#aH5n1 #avianInfluenza #human #occupationalHealth #PPE #updates #USCDC #USA

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/worker-protection-ppe.html

{Excerpt}

Human infections with novel influenza A viruses (such as H5N1 Bird Flu) can happen when enough virus gets into a person's eyes, nose, or mouth, or is inhaled. This can happen when virus is in the air (in droplets, small aerosol particles, or possibly dust) and deposits on the mucus membranes of the mouth, eyes, or nose. It can also happen when a person breathes the virus in, or possibly when a person touches something contaminated by viruses and then touches their mouth, eyes, or nose. Employers should take steps to reduce workers' exposure to novel influenza A viruses from sick animals or contaminated environments. Workers may be exposed when working with animals confirmed or potentially infected with novel influenza A viruses. They may also be exposed when working with materials, including raw milk, that are confirmed or potentially contaminated with novel influenza A viruses.

(…)

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https://etidioh.wordpress.com/2024/11/08/interim-guidance-for-employers-to-reduce-exposure-to-novel-influenza-a-such-as-h5n1-birdflu-for-people-working-with-or-exposed-to-animals/

#aH5n1 #avianInfluenza #birdFlu #flu #health #human #influenza #news #occupationalHealth #PPE #updates #USCDC #USA

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/farm-workers.html

{Excerpt}

Summary

H5N1 bird flu is a virus that has been found in cows. It can also be found in poultry and other animals. People who work with infected animals or their byproducts (for example, raw milk), such as dairy and poultry workers, might get sick from the virus. Your employer should develop a workplace health and safety plan and share it with you. This page was updated to include details about worker exposure levels and using appropriate personal protective equipment safely for each exposure level.

(…)

_____

https://etidioh.wordpress.com/2024/11/08/information-for-workers-exposed-to-h5n1-birdflu/

#aH5n1 #avianInfluenza #human #occupationalHealth #PPE #updates #USCDC #USA

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html

{Excerpt}

Summary

The purpose of this guidance is to outline CDC's recommendations for preventing exposures to highly pathogenic avian influenza (HPAI) A(H5N1) viruses, infection prevention and control measures including the use of personal protective equipment, testing, antiviral treatment, patient investigations, monitoring of exposed persons (including persons exposed to sick or dead wild and domesticated animals and livestock with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) virus), and antiviral chemoprophylaxis of exposed persons. These recommendations are based on available information and will be updated as needed when new information becomes available.

(…)

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https://etidioh.wordpress.com/2024/11/08/highly-pathogenic-avian-influenza-ah5n1-virus-interim-recommendations-for-prevention-monitoring-and-public-health-investigations/

#aH5n1 #antivirals #avianInfluenza #human #oseltamivir #postExposureProphylaxis #PPE #updates #USCDC #USA

Source: Hong Kong PRC SAR, https://www.info.gov.hk/gia/general/202411/08/P2024110800663.htm

{Excerpt}

The Agriculture, Fisheries and Conservation Department (AFCD) was notified today (November 8) by the University of Hong Kong (HKU) that an environmental sample taken from the Mai Po Nature Reserve (MPNR) tested positive for H5N1 subtype highly pathogenic avian influenza virus.

In collaboration with the AFCD, a research team of the School of Public Health, HKU, collects samples from the MPNR regularly for avian influenza surveillance. One of the environmental samples collected on November 6 has been confirmed to be positive for H5N1 virus.

An AFCD spokesman said the World Wide Fund for Nature Hong Kong, the managing organisation of the MPNR, has stepped up cleansing and disinfection of tourist facilities including bird hides and floating boardwalk. Disinfectant carpet has been placed at the entrance of the MPNR for visitors to disinfect the soles of their shoes. In addition, the AFCD is closely monitoring the situation of the birds in the MPNR and has put up notices to remind visitors to pay attention to personal hygiene.

There are no chicken farms within three kilometres of where the sample has been collected. The AFCD has strengthened avian influenza surveillance and been closely monitoring the situation of the local poultry farms and wholesale market. Poultry farmers, pet bird shop owners, and licence holders of bird exhibitions are reminded from time to time to ensure that proper precautions against avian influenza have been implemented.

“People should avoid contact with wild birds and live poultry as well as their droppings. They should clean their hands thoroughly after coming into contact with them. The public can call 1823 for the AFCD’s follow-up if they come across birds suspected to be sick or dead, including the carcasses of wild birds and poultry,” the spokesman said.

(…)

_____

https://etidioh.wordpress.com/2024/11/08/hk-environmental-sample-from-mai-po-nature-reserve-tests-positive-for-h5n1-virus/

#aH5n1 #avianInfluenza #AVIANINFLUENZA #birdFlu #environmentalContamination #h5n1 #health #HKPRCSAR #news #updates

Source: US Centers for Disease Control and Prevention, edited, https://www.cdc.gov/media/releases/2024/t1107-mmwr-telebriefing.html

Please Note: This transcript is not edited and may contain errors.

Operator – 00:00

Welcome and thank you for standing by. At this time, all participants are in a listen only mode until the question and answer session of today's conference. At that time, you may press star one on your phone to ask a question. I would like to inform all parties that today's conference is being recorded. If you have any objections, you may disconnect at this time, I would now like to turn the conference over to Benjamin Haynes, thank you, maybe again.

Moderator – 00:23

Thank you Courtney, and thank you all for joining us today as we release a new MMWR and updated CDC guidance on the H5N1 bird flu outbreaks. We're joined today by Dr. Demetre C. Daskalakis, Director of the National Center for Immunization and Respiratory Diseases and CDC Principal Deputy Director, Dr. Nirav Shah, I'd like to remind everybody that this briefing is embargoed until 1pm Eastern, when our MMWR goes live on the CDC website. I'll now turn the call over to Dr Daskalakis.

Dr. Demetre C. Daskalakis – 00:58

Thank you and good morning everyone. I will first provide an update on H5 cases in the United States. Then we'll share some findings that are being published in an MMWR later today. 

So first, the situation overview. 

To date, there have been 46 human cases of H5 in the US, in 2024 25 cases were due to the ongoing outbreak in dairy cows. 20, which of which are 21, of which are in California. 20 cases are due to poultry depopulation, including the 11 recent cases from Washington State. Additionally, there is one case in Missouri with no known animal or animal product exposure. 

CDC continues to assess the risk to the general population is low. 

Efforts to protect people with exposure to animals or animal products affected by H5 continues to be a key focus of our public health activities. I'd like to now share the results of an important study focused on workers that will be published in the Morbidity and Mortality Weekly Report later today, or MMWR. 

So this is the Michigan Colorado dairy worker survey, CDC, coordinated with state health departments in Michigan and Colorado to conduct an anonymized serosurvey among dairy workers exposed to dairy cows infected with H5N1 influenza A. So as a reminder, a serosurvey is a collection and testing of blood from a defined population. 

In this case, dairy farm workers to estimate the prevalence of antibodies against an infectious pathogen, in this case, H5N1, as an indicator of possible exposure prevalence or immunity. 

The purpose of the serosurvey was to expand our understanding of the extent of infections among exposed dairy farm worker workers, how these infections related to symptoms experienced by participants, and what activities or actions were associated with infection. 

Blood samples were collected from June to August 2024 from 115 people who worked on dairy farms in Michigan and Colorado with cows that were confirmed positive for H5 virus. 

35 of the people included in this serosurvey had results previously reported earlier this summer, and as a reminder, there were dairy farm workers from Michigan and all tested negative for H5N1 antibodies. 

80 additional people were recruited in Michigan and Colorado to increase the sample size of the serosurvey and provide more robust results. 

Samples were collected 15 to 90 days after H5N1 virus was identified in cows on the farm. Along with getting their blood drawn, individuals were interviewed to learn more about what they did on the farm, what protective measures they took, and whether they had been sick since cows on their farms had been diagnosed with H5N1 or quarantine. 

All samples were tested for antibodies against the H5N1 virus isolated from the first human case this year in Texas. And we also tested samples against a seasonal H1N1, virus as a positive control. 

So on to the results, eight of the 115 samples, that's 7% were seropositive against HPAI, or highly pathogenic avian influenza. The 2.3.4.4b A clade that we see circulating among dairy cows using two different antibody tests to be considered antibody or seropositive, both tests had to be positive using accepted criteria. 

Another lab protocol was also performed to remove seasonal influenza antibodies and to rule out that the positive H5N1 tests were due to cross reactivity related to these commonly circulated viruses. 

On to the specific results, 8 of the 115 people tested positive for H5N1 antibodies using this protocol of the seropositive individuals, four remembered having symptoms, mostly conjunctivitis. The other four did not among these four people, illnesses began prior to or shortly after identification of infected herds, more details of who was who had positive results. All eight were Spanish speakers. All eight reported milking cows or cleaning the milking parlor, supporting these as higher risk activities, none wore respiratory protection, and less than half were eye protection, highlighting the need for better tools to support worker protection. Only one person reported they worked with infected cows, despite the fact that they were working with cows on farms with known infection. 

One important limitation to the survey data is that the interviews were conducted on an average 49 days after the first exposure to infected cows with some workers interviewed up to 90 days after their first exposure. That makes recall of minor symptoms potentially difficult. 

Nevertheless, these data help us better understand the potential for infection with mild or no symptoms, as well as highlighting interventions that may help workers reduce their risk of exposure and infection with H5N1.

I’ll now hand the mic over to Dr. Shah, who will go into more details about actions that CDC is taking to further mitigate risk to people who work with animals and animal products potentially affected by H5N1 Dr Shah.

Dr. Nirav Shah – 06:05

Thank you, Dr Daskalakis, and good morning everyone. This is Nirav Shah from CDC, and I'm going to be discussing the steps that CDC is taking in light of the serology results that Dr Daskalakis just outlined. The purpose of these actions is to keep workers safe, to limit the transmission of H5N1 to humans and reduce the possibility of the virus changing right now. 

There are two principal ways that people in the United States are being infected with H5N1 via exposure to infected poultry during culling events, and via exposure to infected dairy cows during the milking process. What we are announcing today is an intensification of recommendations to focus on the highest exposure tasks in poultry and dairy operations, ultimately to reduce the risk of infection. 

We're doing so in three areas. 

Number one, expanding our recommendation for who should be tested for H5N1. 

Number two, a new recommendation for use of Tamiflu for exposed, asymptomatic workers. 

And then number three, focusing our PPE guidance for workers based on their risk of exposure coupled with additional training activities. 

So let's start with testing the serology data that Dr Daskalakis outlined show that there may be individuals who were infected with H5 but who do not recall having symptoms. That means that we in public health need to cast a wider net in terms of who is offered a test so that we can identify, treat and isolate those individuals. Now, previously, as part of an outbreak investigation, we focused on workers who were exposed and who had symptoms. 

Going forward, CDC is expanding our testing recommendation to include workers who were exposed and who do not have symptoms, particularly those workers who were exposed without having worn proper PPE. Again, we're expanding our recommendation to include workers who were exposed and who do not have symptoms, particularly those who were not wearing appropriate PPE. 

The purpose of this expansion, informed by the new serology data, is to actively identify exposed workers with H5, even if their symptoms are so mild as to be unnoticeable, so that those two that those workers too, can be offered treatment and isolation. This active case finding reduces the likelihood that a mild infection could turn into a severe infection, or that the infection spreads to anyone else. 

Simply put, the less room we give this virus to run, the fewer chances it has to cause harm or to change. And the best way to limit the virus's room to run is to test, identify, treat and isolate as many cases as possible in humans and as quickly as possible. 

Second, let's turn to our new recommendation for medication for exposed asymptomatic workers. A key part of our strategy is to offer treatment with Tamiflu to workers who were exposed and who show symptoms that are consistent with H5N1 infection, but in light of the data that Dr Daskalakis outlined, which showed again, the existence of individuals with mild or even no symptoms that they can remember, CDC now recommends offering Tamiflu to asymptomatic workers who had a high risk exposure to H5N1 animals without having worn adequate PPE. 

Again, we are expanding the scope of who CDC recommends Tamiflu for to include now workers who are asymptomatic, who had a high risk exposure to an H5N1 infected animal without having worn adequate PPE. 

So what's at high risk exposure? Well, that could include an unprotected splash in the face with raw cow milk or on the poultry setting, something that might have happened during a depopulation or culling event where the individual was not wearing appropriate PPE. 

Just as with our expanded testing recommendation, more widespread use of Tamiflu achieves several goals. Chief among them is to protect workers. It reduces the likelihood of an asymptomatic case being symptomatic because they're receiving Tamiflu, and thus, it lowers the risk and the chances of onward transmission to close contacts, and then the third thing is our focus on PPE guidance to farms and workers based on their risk level. 

CDC continues to focus on primary prevention strategies like PPE for workers with potential occupational exposures to animals or to animal products that are infected by H5 in light of the serology data. CDC is updating our PPE recommendations for workers based on their risk of workplace exposure going forward. 

CDC PPE recommendations will prioritize what PPE a farm worker should wear based on our data indicating which farm tasks present the highest risk for H5N1, exposure and infection, for example, culling operations or working in the milking parlor with sick or infected animals, simply put, the higher risk activities will call for more PPE use. 

CDC has developed additional resources to support training workers on PPE use and to explain its role in preventing H5N1 from animals infecting humans. 

CDC will continue to evaluate this situation and will update our guidance as needed. To close, what we've discussed today is an example of CDC using data to drive action. We will continue working with trusted partners to reach farm workers and their employers to communicate these prevention strategies as widely as possible. And then finally, before we open it up to questions, we will, we anticipate publishing a spotlight today that contains these updated recommendations. With that, we'll turn it over back to our team for questions.

Moderator 12:34

Thank you. Dr. Shah. We are now ready to open up for questions.

Operator – 12:39

Thank you. We will now begin the question and answer session. If you would like to ask a question, please press star one. If you need to withdraw your question, press star two. Again to ask a question, please press star one. Our first question comes from Brenda Goodman from CNN.

Brenda Goodman – CNN – 12:58

Thank you so much for taking my question and congratulations on these studies, because I know you had some significant headwinds to get them done. I have a question about the eight workers, are they counted as cases now? Or will they be counted as cases in the human case count? And then I was curious. You gave an update at the beginning. Dr Daskalakis about how many human cases of H5 were associated with poultry depopulations this year. Why do you think we're so many seeing so many more human infections with poultry depopulation because we've had age five in poultry before, and I think we only had one case prior this year.

Dr. Demetre C. Daskalakis – 13:38

Great. Thank you for those questions. So on the first question, these retrospective serologies are not going to be reported as cases, so they are really looking retrospectively, helping us learn, but they're not going to be called cases. On the second question, I think there are a lot of reasons why we could potentially be seeing more human disease related to or human infections related to the culling operations. 

One is there's more H5, so that's probably one of the most important. Like both in wild birds as well as in poultry, we're seeing a significant increase, and the more the sort of H5 community viral load is high in animals, the more likely it is that humans will be exposed. 

I think the second is also that we, I think, have raised a lot of attention to carefully screening individuals with H5 exposure for even mild symptoms. So there could be that as well. 

In terms of other characteristics of the virus, we are not seeing any changes with the virus that would indicate ease of transmission. But given sort of our current environment, the sort of increasing experience with age five and one really creating strategies to better protect workers based on this data is, I think, the right thing to do at this time.

Operator – 15:00

Our next question comes from Megan Molteni from STAT

Megan Molteni from STAT – 15:06

Thanks for taking my question. I was wondering if you could clarify something that you said about only one of the persons who tested positive for antibodies reporting having worked with known infected cows, and it sounded like you were saying that that meant there was a need for more additional education. But could it also be that these animals that they're working with are asymptomatic, and so, you know, they're going through the milking parlors and they're not getting separated out into quarantine? Can you talk a bit about what we know about asymptomatic disease in the animal.

Dr. Demetre C. Daskalakis – 15:41

Great. Thank you. So. So I think that you put the nail on the head that this is really about about education and also self-assessment of risk, which I think is an important piece of both why one would wear post, why one would wear appropriate PPE as well as pursue post exposure prophylaxis. So these were farms with known infected cows, and so it was really about the fact that they didn't have the awareness that they had any sick cows that they were working with, even though they were in environments where sick cows were known. So it really speaks to the importance of more on farm training around H5 as well as ways to protect from H5

Megan Molteni from STAT – 16:22

Okay, thank you. Can you also just, very quickly, are there any more serology studies planned in other states, like thinking about California, given the number of herds we see there now.

Dr. Demetre C. Daskalakis – 16:33

Thank you for that question. So we are currently working, and I think we've, we've put this up on one of our prior spotlights on a serology study, a serosurvey, that is that was conducted it physically in Ohio, because there was a large convention of bovine practitioners, and so we about 150 of them provided blood samples as well as survey data. And we will update on those once they become available.

Operator – 17:04

Our next question comes from Josh Nathan-Kazis from Barrons.

Josh Nathan-Kazis from Barrons – 17:08

Sorry. Thank you so much. Two quick questions. One, I wonder if you could have some context. I mean, how unexpected is it that there would be asymptomatic HVAC cases? That's something that's been seen before elsewhere. How much of a surprise of the finding and separately I saw in the MMWR says that 40% of the workers reported feeling ill while H5 was on their farm, although only a fraction of those actually had serological evidence of infection. I wonder, if you just talk about what might be going on there and why so many of the workers said they felt sick, even if their blood tests didn't say they were sick.

Dr. Demetre C. Daskalakis – 17:46

Thank you. So on the first question, I think that the only way to sort of take out surprises by doing the studies, which is why it's important that we have that information. 

But I think given the mildness of the symptoms that many people are presenting with, it's not a surprise that some people wouldn't recall symptoms up to 90 days after their exposure. 

So again, though not surprising, it actually is approximately in line with other serosurveys that have been conducted that focused on, on, again, this specific clade of H5N1, so a study that happened in workers, 2223 showed about 4.6% were seropositive, and about 14% as you recall from a pre print that UT Galveston Galveston put out in early 2024 also showed asymptomatic individuals with infection. 

So again, not surprising, but in line with some of the other data. 

Now, question two, not every respiratory symptom is related to H5N1. And so we've actually seen in other environments that there is several other viruses that could explain respiratory symptoms. 

So in this circumstance, though there was not serology done for other respiratory symptoms, that likelihood is that the illnesses that they that they experienced, were not caused by H5N1 based on our testing criteria. Over,

Dr. Nirav Shah – 19:13

Hey Josh, this is Nirav. One other point you noted, or you framed some of these results as asymptomatic, the structure of the survey itself doesn't demonstrate whether these individuals were asymptomatic or whether they just couldn't remember having had symptoms. 

And so the most we can say is that they can't remember having had symptoms. Some of them may have had mild symptoms that, again, were unmemorable. Some of them may have been indeed asymptomatic. The data that we have does not allow us to determine which of those it was, and so for that reason, we're not characterizing these as asymptomatic. All we can say is that they don't recall having had symptoms.

Operator – 19:55

Our next question comes from Erica Edwards.

Erica Edwards – 20:00

Hey, thanks so much. I appreciate the opportunity. And a couple questions. One is about the severity of H5N1 illness in people. I mean, obviously previous estimates from other areas of the world have quoted mortality rate of at least 50% I'm curious what you're learning about from studying the H5N1 infections here in the US that I think would be quite mild. What's different here? And then, if I also could ask, could you talk about any work that's being done to develop rapid tests, H5N1? Thank you.

Dr. Demetre C. Daskalakis – 20:32

Thanks for that question. So on, the severity, again, what we've been seeing in the United States is extremely mild symptoms. 

So again, ranging from moderate to mild conjunctivitis, and some people also experiencing mild respiratory symptoms, and also some with constitutional symptoms, like there have been some folks with beavers. 

So, you know, I think that there are a couple of hypotheses, which is all that we can really provide as to why there's a difference in severity. 

One, you know though, though H, all, H, 5n, ones are not built the same. So these are actually potentially different genotypes. So we know that there's sort of different clades and genotypes circulating. 

So what we have in the US at this point has only caused mild illness. 

Also, there could be issues related to the populations that are exposed to the virus, as well as to the magnitude of the exposure. So again, all hypotheses. So we don't have a very clear answer, but from the perspective of what we're seeing in the US, everything has been mild.

Dr. Nirav Shah – 21:40

And then this is Nirav on your latter question around rapid tests. So CDC has been working very closely with our colleagues at NIH particularly their rad X program, to evaluate some of the rapid diagnostic tests that are already available on the market, to determine whether those tests are capable of detecting H5 These are tests that can already detect influenza A, influenza B, sometimes even COVID in general. 

But the question is, can they detect H5 the current circulating version of H5 as part of their overall diagnostic approach? And CDC has been collaborating with our NIH colleagues to try to understand the utility of those tests. We don't have a timeline on when those data will be available, but I know that work is underway right now. 

Separately, we've been working with diagnostics companies to determine what types of additional rapid tests might be useful in the marketplace to try to move or shorten the duration between becoming symptomatic or exposed and then being able to have access to testing. Clearly rapid test still an important niche there, so we're very much in favor of them. We've just got to make sure that they are capable of serving that purpose.

Dr. Demetre C. Daskalakis – 22:48

Just one other thing to add is CDC will also be working with with a couple of states, to do a testing pilot where we're actually assessing a near point of care, or point of care test against lab based testing for H5, so that will also help elucidate some point of care strategies or or self-testing that may help in the future.

Operator – 23:15

Our next question comes from Washington Post.

Washington Post – 23:21

Hi. Thanks for taking this call. Two questions. One, you mentioned one of the justifications for these precautionary measures being preventing onward spread, but we've also been hearing there's no evidence of human to human transmission. So does this new data create any concerns that some of these dairy workers may have been spreading the virus among each other, and then the second one is now that we have an incoming administration that's promised mass deportations. Are you worried about about a cooperation with these, investing with these investigate public health investigations in the future? Would you get the same kind of cooperation that you did with with workers, if there's a potential, if there's mass deportations looming, great

Dr. Nirav Shah – 24:07

This is Nirav as to the former question, I'm glad you raised that for avoidance of doubt and for clarity, there is nothing that we've seen in the new serology data that gives rise to a concern about person to person transmission. So to your point that you made about, why are we going this extra step with additional testing and Tamiflu to further in that regard? And the answer is to drive that risk down as low as possible. This is fundamentally a respiratory virus, and although we have not seen changes to the virus that would suggest the capacity for it to spread from person to person. 

We want to keep that risk as low as where it is right now, one of the best ways to do that is to identify individuals who have been exposed through greater testing and provide them with Tamiflu to drive down the levels of virus in their body, which, again. Helps us keep that low risk as low as possible. As to your latter question, we're not commenting on anything related to transition or an incoming administration. We're focused today on the serology data and the CDC actions therein. Thanks,

Moderator – 25:15

Cortney. We have time for two more questions, please.

Operator – 25:19

Our next question comes from Youri Benadjalud from ABC News.

Youri Benadjalud from ABC News – 25:22

Thanks for taking my question. This data seems to support that there are a lot of cases that are potentially being undercounted, and there's only 46 confirmed by the CDC so far. How many cases in across forums, in the US, do you think that could actually be out there? And then I'll have a follow up, please.

Dr. Nirav Shah – 25:43

Thanks Yuri. Our data suggests that there in any outbreak situation, we know that there are individuals who may have been exposed, may have been infected, who are not part of the count. This is what serology data helps us get a better retrospective understanding of we still need more data to better characterize that so we can't speculate today on how many unidentified cases that there might be. We've always known that that's a possibility. What these data really help us understand is that some of those workers may have had such mild symptoms, such that they may not recall having been ill, and thus we need to identify those individuals and make sure they've got medication, as I said, in connection with the prior question, to drive their risk of getting ill as far as possible down, as well as to reduce the likelihood of spread. But better characterizing right now, how much of the iceberg is above the water versus below the water. It's not something we have enough data on quite yet.

Operator – 26:43

Our last question was from Kai Kuperschmid from Himes Magazine.

Kai Kuperschmid from Himes Magazine – 26:51

Thanks for taking my question. So I wanted to ask a little bit about the timeline. Here you said the the samples were taken, I think June to August. It's November now, and just in general, I mean, it's taken a long time to get this kind of data. I know a lot of people have been waiting for it. Can you describe a little bit why it took this long, and what the hurdles are to do this, also to do it in other places, possibly. Thanks guys.

Dr. Demetre C. Daskalakis – 27:14

So I think a lot of the timeline is really around just sort of the standard procedures for serology for H5. So the first is again, we had to sort of gather the specimens. They had to come to CDC. And then the subsequent pieces are that these 115 specimens had to be run in our BSL, three labs that, as increasing data emerged, the cross reactivity with seasonal flu became something that we needed to be addressing in the testing. We then had to develop additional protocols to do the adsorption for seasonal flu, then run the absorption and then rerun the tests again. So this was released, really at a good time and a good timeline, given the complexity of non-routine laboratory testing that was needed to be able to characterize these individuals. Thanks for your question.

Moderator – 28:10

I’d like to thank you all for joining us today. If we did not get to your question, or if you have follow up questions, please feel free to call the main CDC press office at 404-639-3286 or you can email [email protected] Thank you for joining us, and this will conclude our call.

That concludes today’s conference. Thank you for participating. You may disconnect at this time.

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https://etidioh.wordpress.com/2024/11/08/transcript-for-mmwr-telebriefing-evidence-of-recent-h5-birdflu-infections-among-dairy-workers-and-cdc-guidance-updates/

#aH5n1 #antivirals #avianInfluenza #AVIANINFLUENZA #birdFlu #h5n1 #health #human #news #oseltamivir #PPE #serology #updates #USCDC #USA

Source: US Centers for Disease Control and Prevention, MMWR Morbidity and Mortality Weekly Report, https://www.cdc.gov/mmwr/volumes/73/wr/mm7344a3.htm?s_cid=mm7344a3_e&ACSTrackingID=USCDC_921-DM140166&ACSTrackingLabel=This%20Week%20in%20MMWR%3A%20Vol.%2073%2C%20November%207%2C%202024&deliveryName=USCDC_921-DM140166

Summary

What is already known about this topic?

Infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected sporadically in dairy farm workers in the United States since April 2024. Public health response efforts include active monitoring of workers exposed to HPAI A(H5) virus for illness.

What is added by this report?

Health officials conducted surveys and serologic testing to identify recent HPAI A(H5) infections among dairy workers in two states. Serologic testing indicated that 7% of participating dairy workers had evidence of recent infection with HPAI A(H5) virus.

What are the implications for public health practice?

The findings support the need for active monitoring of exposed workers and testing to detect and treat HPAI A(H5) infections, including those in persons with very mild symptoms. These efforts should be coupled with farmworker education about infection risks and prevention measures.

Abstract
Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June–August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers. In both states, a convenience sample of persons who work in dairies was interviewed, and blood specimens were collected. Among 115 persons, eight (7%; 95% CI = 3.6%–13.1%) had serologic evidence of recent infection with A(H5) virus; all reported milking cows or cleaning the milking parlor. Among persons with serologic evidence of infection, four recalled being ill around the time cows were ill; symptoms began before or within a few days of A(H5) virus detections among cows. This finding supports the need to identify and implement strategies to prevent transmission among dairy cattle to reduce worker exposures and for education and outreach to dairy workers concerning prevention, symptoms, and where to seek medical care if the workers develop symptoms. Timely identification of infected herds can support rapid initiation of monitoring, testing, and treatment for human illness, including mild illness, among exposed dairy workers.

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https://etidioh.wordpress.com/2024/11/07/serologic-evidence-of-recent-infection-with-highly-pathogenic-avian-influenza-ah5-virus-among-dairy-workers-michigan-and-colorado-june-august-2024-7-of-workers-were-posi/

#aH5n1 #abstract #avianInfluenza #AVIANINFLUENZA #birdFlu #colorado #dairyCow #h5n1 #health #human #michigan #news #occupationalHealth #research #serology #USCDC #USA

Source: US Centers for Disease Control and Prevention, MMWR Morbidity and Mortality Weekly Report, https://www.cdc.gov/mmwr/volumes/73/wr/mm7344a2.htm?s_cid=mm7344a2_e&ACSTrackingID=USCDC_921-DM140166&ACSTrackingLabel=This%20Week%20in%20MMWR%3A%20Vol.%2073%2C%20November%207%2C%202024&deliveryName=USCDC_921-DM140166

Summary:

What is already known about this topic?

Use of personal protective equipment (PPE) by farmworkers can protect them when they are working with highly pathogenic avian influenza A(H5N1)–infected cows.

What is added by this report?

Dairy farmworkers in Colorado who were interviewed about PPE use during work activities with ill cows reported 28% higher use of PPE after detection of A(H5N1) virus on the farm than before detection, including a 40% increase in reported use of eye protection during milking. Reported use of respirators and other masks was low.

What are the implications for public health practice?

Establishing strong relationships between public health agencies and agricultural organizations to communicate public health risk and protective practices on U.S. farms after detection of A(H5N1) in cows, and early distribution of PPE before A(H5N1) virus detection, might increase PPE use once an A(H5N1) outbreak is identified.

Abstract
The risk for transmission of highly pathogenic avian influenza A(H5N1) virus from dairy cows to humans is currently low; however, personal protective equipment (PPE) use during work activities on dairy farms has not been well described. PPE use can protect farmworkers when they are working with highly pathogenic avian influenza A(H5N1)–infected cows. The Colorado Department of Public Health and Environment (CDPHE) and the Colorado Department of Agriculture (CDA) offered PPE to all Colorado farms before or during an A(H5N1) outbreak in cows in 2024. CDPHE surveyed 83 dairy workers from three farms with a confirmed bovine A(H5N1) outbreak. Frequently reported farm worker activities included milking cows or working in the milking parlor (51%), cleaning cow manure (49%), and transporting cows (46%). Frequently reported PPE items available to workers before A(H5N1) outbreaks included gloves (88%), eye protection (e.g., safety glasses or goggles) (76%), rubber boots or boot covers (71%), and head covers (69%). N95 respirator use was low among workers who were exposed to ill cows after detection of A(H5N1) virus (26%). PPE use while working with ill cows increased a mean of 28% after detection of A(H5N1) virus on surveyed farms; use of eye protection while milking cows increased the most (40%). Public health PPE distribution, education, and collaboration with CDA might have increased PPE use on dairy farms with A(H5N1) virus–infected cows and mitigated risk for farmworkers acquiring A(H5N1) virus.

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https://etidioh.wordpress.com/2024/11/07/ppe-use-by-dairy-farmworkers-exposed-to-cows-infected-with-highly-pathogenic-avian-influenza-ah5n1-viruses-colorado-2024/

#aH5n1 #abstract #avianInfluenza #AVIANINFLUENZA #birdFlu #colorado #dairyCow #h5n1 #health #news #occupationalHealth #PPE #research #USCDC #USA

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.01.621606v1?rss=1

Abstract
The ongoing outbreak of highly pathogenic avian influenza (HPAI) H5N1 of the clade 2.3.4.4b in dairy cows has led to numerous questions including how the virus transmits amongst cattle given the limited respiratory infection. One hypothesis is that the virus is spreading through fomites from udder to udder. In these studies, we demonstrate that intraductal inoculation of H5N1 but not H1N1 influenza virus results in infection in mice. This model will be useful to our understanding of the impact of influenza virus on the mammary gland, the potential as a new route of transmission, and can be used to assess if antiviral treatments prevent infections in the mammary gland.

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https://etidioh.wordpress.com/2024/11/03/intraductal-infection-with-h5n1-clade-2-3-4-4b-influenza-virus/

#aH5n1 #abstract #animalModels #avianInfluenza #dairyCow #research

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/spotlights/ah5n1-ferret-study-results.html

{Excerpt}

What to know
The results of CDC's first study looking at the effects on ferrets of an avian influenza A(H5N1) virus from a human case in Texas have been published in Nature. CDC first shared preliminary findings from this study, which were instrumental in informing early risk assessments related to this outbreak, in June 2024. Ferrets are used as a model to assess the disease and spread characteristics of specific influenza (flu) viruses in people. The initial study was subsequently replicated to confirm the findings, and this publication summarizes all the findings from the ferret experiments using the isolate from the case human case in Texas. Results of subsequent similar studies using different viruses from the same outbreak have differed.

(…)

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https://etidioh.wordpress.com/2024/11/01/us-cdc-reports-additional-avian-influenza-ah5n1-ferret-study-results/

#aH5n1 #animalModels #avianInfluenza #ferrets #human #research #USCDC #USA

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.10.29.620905v1

Abstract
The host range of HPAIV H5N1 was recently expanded to include ruminants, particularly dairy cattle in the United States. Shortly after, human H5N1 infection was reported in a dairy worker in Texas following exposure to infected cattle. Herein, we rescued the cattle-origin influenza A/bovine/Texas/24-029328-02/2024(H5N1, rHPbTX) and A/Texas/37/2024(H5N1, rHPhTX) viruses, identified in dairy cattle and human, respectively, and their low pathogenic forms, rLPbTX and rLPhTX, with monobasic HA cleavage sites. Intriguingly, rHPhTX replicated more efficiently than rHPbTX in mammalian and avian cells. Still, variations in the PA and NA proteins did not affect their antiviral susceptibility to PA and NA inhibitors. Compared to rHPbTX and rLPbTX, the rHPhTX and rLPhTX exhibited higher pathogenicity and efficient replication in infected C57BL/6J mice. The lungs of rHPhTX-infected mice produced higher inflammatory cytokines/chemokines than rHPbTX-infected mice. Our results highlight potential risk of HPAIV H5N1 virus adaptation in human and/or dairy cattle during the current multistate/multispecies outbreak.

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https://etidioh.wordpress.com/2024/10/30/replication-kinetics-pathogenicity-and-virus-induced-cellular-responses-of-cattle-origin-influenza-ah5n1-isolates-from-texas-united-states/

#aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #dairyCow #h5n1 #health #human #news #research

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.10.23.619695v1

Abstract
The most recent outbreak of highly pathogenic avian H5 influenza (HPAI) virus in cattle is now widespread across the U.S. with spillover events happening to other mammals, including humans. Several human cases have been reported with clinical signs ranging from conjunctivitis to respiratory illness. However, most of those infected report mild to moderate symptoms, while previously reported HPAI H5Nx infections in humans have had mortality rates upwards of 50%. We recently reported that mice with pre-existing immunity to A/Puerto Rico/08/1934 H1N1 virus were protected from lethal challenge from highly pathogenic clade 2.3.4.4b H5N1 influenza virus. Here, we demonstrate that mice infected with the 2009 pandemic H1N1 virus strain A/California/04/2009 (Cal09) or vaccinated with a live-attenuated influenza vaccine (LAIV) were moderately-to-highly protected against a lethal A/bovine/Ohio/2024 H5N1 virus challenge. We also observed that ferrets with mixed pre-existing immunity, either from LAIV vaccination and/or from Cal09 infection, showed protection against a HPAI H5N1 clade 2.3.4.4b virus isolated from a cat. Notably, this protection occurred independently of any detectable hemagglutination inhibition titers (HAIs) against the H5N1 virus. To explore factors that may contribute to protection, we conducted detailed T cell epitope mapping using previously published sequences from H1N1 strains. This analysis revealed a high conservation of amino acid sequences within the internal proteins of our bovine HPAI H5N1 virus strain. These data highlight the necessity to explore additional factors that contribute to protection against HPAI H5N1 viruses, such as memory T cell responses, in addition to HA-inhibition or neutralizing antibodies.

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https://etidioh.wordpress.com/2024/10/24/immune-history-modifies-disease-severity-to-hpai-h5n1-clade-2-3-4-4b-viral-challenge/

#aH1n1 #aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #ferrets #h1n1pdm09 #h5n1 #health #immuneSystem #news #research

RT @ECDC_Outbreaks: Our weekly bulletin on active #PublicHealth threats is out now!

This issue focuses on:
- #COVID19,
- #strepA
- #influenza & #influenza #AH5N1
- #MERS
- #Mpox
- #poliomyelitis
- #Marburg virus disease
- Earthquakes in Türkiye & Syria.

Read: https://www.ecdc.europa.eu/en/publications-data/communicable-disease-threats-report-week-9-27-february-5-march-2023

🐦🔗: https://n.respublicae.eu/ECDC_EU/status/1631720184632229888

Enorme la crisis sanitaria que enfrenta México ante la #InfluenzaAviar #AH5N1 que ya se extiende por 10 estados del país.

Ante la irresponsabilidad del gobierno federal, Francisco Javier Trujillo renuncia al #SENASICA después de 25 años de impecable trayectoria.

Lamentable.

Enorme la crisis sanitaria que enfrenta México ante la #InfluenzaAviar #AH5N1 que ya se extiende por 10 estados del país.

Ante la irresponsabilidad del gobierno federal, Francisco Javier Trujillo renuncia al #SENASICA después de 25 años de impecable trayectoria.

Lamentable.

Enorme la crisis sanitaria que enfrenta México ante la #InfluenzaAviar #AH5N1 que ya se extiende por 10 estados del país.

Ante la irresponsabilidad del gobierno federal, Francisco Javier Trujillo renuncia al #SENASICA después de 25 años de impecable trayectoria.

Lamentable.