A newly emergent N1 #neuraminidase associated with clade 2.3.4.4b highly pathogenic avian #influenza #H5 viruses in North #America

 

Abstract

We investigated the evolutionary history of the newly emergent neuraminidase (am4N1) associated with the D1.1 and D1.2 genotypes of highly pathogenic avian influenza A(H5N1) viruses in North America. Phylogenetic inference places am4N1 in a sister clade to Eurasian avian, swine, and human A(H1N1)pdm09 viruses and distinct from 1918, pre-2009 human seasonal, and classical swine A(H1N1) lineages. Am4N1 descends from diverse avian N1 genes endemic to the Americas. Phylodynamic analysis indicates a monophyletic am4N1 lineage with numerous introductions of viruses carrying the am4N1 gene likely originating from western Canada into the United States during emergence of the D1.1 and D1.2 genotypes. The lineage has diversified and accumulated deletions in the stalk domain. Despite amino acid divergence, structural modeling shows conserved neuraminidase architecture in the globular head. Given its distinct ancestry and amino acid sequence, further studies are needed to assess cross-reactivity of antibodies from prior human A(H1N1)pdm09 infections.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study did not receive any external funding.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.03.09.26347929v1

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Loss of α2,3-linked #sialoside in the receptor-binding site of a #H5N1 #influenza hemagglutinin identified in a #human patient

 

Abstract

In November 2024, an adolescent female in British Columbia was hospitalized presenting with severe symptoms including respiratory failure due to infection with a novel H5N1 subtype influenza strain (BC24). Using cryogenic electron microscopy (cryo-EM), we show here that the N169 α2,3-linked auto-glycan that is found in the sialic acid binding site of previously studied H5 hemagglutinin (HA) proteins is absent in purified BC24 HA protein, suggesting greatly reduced affinity for α2,3-linked sialosides. Glycan microarray analysis shows that the BC24 HA protein displays reduced or no binding not just to most α2,3-linked sialosides, but also to α2,6-linked sialosides. Full-length BC24 HA expressed in A549 lung alveolar carcinoma cells drives membrane fusion, albeit at significantly lower levels than previous H5 HA proteins, and post-infection sera from the patient display strong binding to BC24 HA and HA proteins from other influenza subtypes. The high virulence of the BC24 strain despite weak receptor binding reveals further complexity in the factors that result in severe disease caused by avian influenza.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Canada Biomedical Research Fund

Canada Excellence Research Chairs, https://ror.org/02tvrwm90

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.01.19.700419v1

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#Management of #critical illness in an #adolescent caused by highly pathogenic avian #influenza #H5N1 virus infection in #BC, #Canada

 

Summary

Highly pathogenic avian influenza A(H5N1) viruses have been circulating among wild birds and are enzootic in poultry in some areas of the world with spillover to a wide range of terrestrial and marine mammals. Since 1997, sporadic animal to human, primarily poultry to human, transmission of highly pathogenic avian influenza A(H5N1) viruses has been reported in 25 countries. More recently there have been locally acquired infections in the Americas due to the 2.3.4.4b clade of the virus. Most of the recently detected human infections in the USA have been relatively mild but there have been cases of critical illness reported in several countries. In this Grand Round we present the first locally acquired highly pathogenic avian influenza A(H5N1) virus infection in Canada, which was in a 13-year-old female, who developed severe disease requiring prolonged critical care. She was infected with a clade 2.3.4.4b, genotype D1.1 virus and developed evidence of cytokine storm and received several modalities of care including combination antiviral therapy, renal replacement therapy, therapeutic plasma exchange, and invasive mechanical ventilation support with veno-venous extracorporeal life support. She recovered and was discharged home without requirement for additional support. This Grand Round describes important clinical and management considerations for critically ill patients infected with highly pathogenic avian influenza A(H5N1) virus.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00773-X/abstract?rss=yes

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#Macrolide #Resistance and P1 Cytadhesin Genotyping of #Mycoplasma pneumoniae during #Outbreak, #Canada, 2024–2025

 

Abstract

We investigated macrolide resistance and P1 genotypes of Mycoplasma pneumoniae during the 2024–2025 outbreak in Hamilton, Ontario, Canada. Macrolide resistance remained stable at ≈10%–20%, but significant shifts in P1 genotype distribution and resistance rates in P1 types occurred, indicating notable changes in M. pneumoniae molecular epidemiology in Ontario since 2011–2012.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/31/12/25-0872_article

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#Zoonotic and #Avian #Pathogen Detections in Fecal and Sediment #Samples - A Low-risk, High-throughput One Health Approach to #Surveillance

 

Abstract

Many pathogens, both those with human spillover potential as well as avian-specific viruses, are maintained in wild bird populations. While much surveillance for influenza A viruses (IAVs) is performed annually, surveillance for other pathogens is limited. Sampling of wild birds is often time-consuming, labour-intensive, involves physically handling wild birds, often limited in sample size, and involves handling of potentially infected birds, posing an increased risk of direct exposure for personnel. Given this, additional methods for surveillance are needed. Longitudinal, bi-weekly fecal and sediment sampling was performed at various sites in southern Manitoba, Canada, particularly focused in Winnipeg from May - October 2025. Sites were chosen based on the suitability of the area for waterfowl habitat, the presence of waterfowl in the area, as well as sites in proximity to reported outbreaks of H5N1 influenza virus. Fecal and sediment samples were collected and screened for the presence of influenza A virus (IAV), Newcastle disease virus (NDV), avian reovirus (ARV), and avian poxvirus (APXV). In total, 782 combined fecal and sediment samples were collected. Of the 714 fecal samples, 34 tested positive for IAV (4.8% prevalence). None of the IAV-positive fecal samples tested positive for H5 RNA. Of the 68 sediments tested, 15 tested positive for IAV (22.1% prevalence), four of which further tested positive for H5 RNA. NDV positivity was low, with only four positive fecal samples (0.56% prevalence) that were all collected on the same day. ARV positivity was also low, with five positive sediment samples (7.4% prevalence in sediment samples). Of the 782 total samples collected, of 559 samples that have been tested for APXV to date, all have tested negative. This work expands upon previous work showing the utility of environmental sampling for a variety of avian and zoonotic pathogens using a One Health approach that is both high-throughput and low-risk.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Canadian Institutes of Health Research, Tier 2 Canada Research Chair, 950 231498

Natural Sciences and Engineering Research Council, RGPIN-2018-06036

Source: 

Link: https://www.biorxiv.org/content/10.64898/2025.12.19.694637v1

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Serological #Evidence of Highly Pathogenic Avian #Influenza #H5N1 in Invasive Wild #Pigs in Western #Canada

 

Abstract

Influenza A virus (IAV) can infect a wide range of hosts, including wild and domestic pigs. Swine play an important role in influenza evolution and epidemiology due to their ability to get infected with both avian and human influenza viruses, potentially leading to reassorted virus variants. Interactions at the wild-domestic swine interface have been documented on multiple occasions, raising concern about pathogen transmission and the emergence of novel influenza strains. This study investigates the occurrence and subtypes of IAV infecting invasive wild pigs in Alberta, Canada. A total of 267 wild pigs were captured between 2021–2024. Exposure to IAV was initially detected by cELISA, with further confirmation of exposure to the H5Nx virus by hemagglutination inhibition (HI) and virus neutralization (VN) assays. Although no IAV genetic material was detected by qPCR, the seropositive samples by cELISA (4.17%; 5/120) coincided with the 2022–2024 highly pathogenic avian influenza virus (HPAI) H5N1 epizootic in Alberta, which involved outbreaks in wild species and domestic birds. These findings, combined with the epidemiological context, suggest interspecies transmission of HPAI H5N1 clade 2.3.4.4b to wild pigs. These results highlight the potential role of wild pigs as a new host in Canada and emphasize the need for continued surveillance of IAV in wild pig populations to assess the risk of spillover events at the wildlife, livestock, and human interfaces.

Source: 

Link: https://onlinelibrary.wiley.com/doi/10.1155/tbed/2720469

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Cross-reactive #neuraminidase inhibition #antibodies against #H5N1 by consecutive #influenza A imprinting cohorts of the past century: population-based serosurvey, British Columbia, #Canada

 

Abstract

Background: 

Avian influenza of the H5N1 subtype shares substantial relatedness in its neuraminidase (NA) surface protein with human influenza A H1N1 viruses of the past century. Understanding variation in pre-existing anti-N1 antibodies against H5N1 is critical to pandemic risk assessment and preparedness. 

Methods: 

We used anonymized, residual sera collected equally from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey in British Columbia, Canada. We assessed NA inhibition antibody titres by enzyme-linked lectin assay against H5N1 (N=575), H1N1pdm09 (N=250) and H3N2 (N=205). We compared anti-NA titres by birth (imprinting) cohorts defined in relation to historic N1 and/or N2 exposure opportunities. 

Results: 

Among participants with median age 32 (IQR: 15-62) years, 404 (70%) had cross-reactive anti-N1 titre ≥10 against H5N1, with 260 (45%), 182 (32%) and 98 (17%), having titres ≥40, ≥80 and ≥160, respectively. H5N1 titres were consistently lower but strongly associated with H1N1pdm09 (r=0.86; 95%CI:0.82-0.89). Geometric mean titres against H1N1pdm09 and H5N1 peaked among young adults born 1997-2003 (427.9, 100.8), declining to lows among young children born 2015-2023 (20.7, 6.8) and middle-aged adults born 1957-1967 (25.1, 10.7), increasing to similar secondary peak among older adults born pre-1947 (387.3, 81.0). 

Conclusions: 

A substantial proportion of the population has pre-existing, cross-reactive anti-N1 antibodies against H5N1. We interpret variation by age and imprinting cohorts within a unifying hypothesis, emphasizing the role of historic influenza pandemics in expanding and refining the immune repertoire through heightened attack rates and shifts in immunological hierarchies. Our findings have implications for H5N1 and other zoonotic influenza risk assessment.

Competing Interest Statement

DMS is Principal Investigator on grants received to her institution from the Public Health Agency of Canada, Pacific Public Health Foundation, Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research for unrelated work. As the Provincial Health Officer with authority under the emergency provisions of the Public Health Act, BH authorized the provision and analysis of the anonymized sera used in this study; the study was separately reviewed and approved by the UBC Clinical Research Ethics Board and Health Canada-Public Health Agency of Canada Research Ethics Board. No other competing interests were declared.

Funding Statement

This work was supported by the Public Health Agency of Canada (Grant number: 2021-HQ-00067), received by the Institution of DMS. The views expressed herein do not necessarily represent the views of the Public Health Agency of Canada.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.19.25336209v1

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Intensive #transmission in wild, migratory #birds drove rapid geographic #dissemination and repeated #spillovers of #H5N1 into agriculture in North #America

Abstract

Since late 2021, a panzootic of highly pathogenic H5N1 avian influenza virus has driven significant morbidity and mortality in wild birds, domestic poultry, and mammals. In North America, infections in novel avian and mammalian species suggest the potential for changing ecology and establishment of new animal reservoirs. Outbreaks among domestic birds have persisted despite aggressive culling, necessitating a re-examination of how these outbreaks were sparked and maintained. To recover how these viruses were introduced and disseminated in North America, we analyzed 1,818 Hemagglutinin (HA) gene sequences sampled from North American wild birds, domestic birds and mammals from November 2021-September 2023 using Bayesian phylodynamic approaches. Using HA, we infer that the North American panzootic was driven by ~8 independent introductions into North America via the Atlantic and Pacific Flyways, followed by rapid dissemination westward via wild, migratory birds. Transmission was primarily driven by Anseriformes, shorebirds, and Galliformes, while species such as songbirds, raptors, and owls mostly acted as dead-end hosts. Unlike the epizootic of 2015, outbreaks in domestic birds were driven by ~46-113 independent introductions from wild birds, with some onward transmission. Backyard birds were infected ~10 days earlier on average than birds in commercial poultry production settings, suggesting that they could act as early warning signals for transmission upticks in a given area. Our findings support wild birds as an emerging reservoir for HPAI transmission in North America and suggest continuous surveillance of wild Anseriformes and shorebirds as crucial for outbreak inference. Future prevention of agricultural outbreaks may require investment in strategies that reduce transmission at the wild bird/agriculture interface, and investigation of backyard birds as putative early warning signs.

Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.16.628739v2

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A #Genome #Sequence Variant #Monitoring Program for Seasonal #Influenza #H3N2 & #RSV using #Wastewater-Based #Surveillance in #Ontario, Canada

Abstract

Seasonal respiratory viruses, such as the Influenza A virus and the respiratory syncytial virus, are responsible for over a billion infections worldwide each year resulting in a substantial burden on health care systems. Surveillance of these viruses, including their prevalence in communities and their evolution, are essential for informing public health decisions and recommending vaccine formulations and schedules. Typically, these viruses are monitored using clinical samples from patients seeking medical attention. Recently, wastewater-based surveillance (WBS) has been leveraged to understand transmission dynamics and genome evolution of SARS-CoV-2 and seasonal respiratory viruses. To further the utility of WBS we developed and implemented novel tiled-amplicon sequencing assays to identify and track Influenza A virus H3N2 and respiratory syncytial virus A circulating in Southern Ontario, Canada. We also developed virus specific deconvolution tools to estimate the abundance of mixed lineages in wastewater. These assays were able to accurately determine which lineages were circulating in wastewater with high sensitivity and specificity. If implemented in regular surveillance programs, they could be used to inform real-time public health decisions and determine potential disease surge with impact on emergency room visits and hospitalization, as well as track which emerging strains will become predominant in the future and determine which strains should be the focus of seasonal vaccines.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Integrated Network for the Surveillance of Pathogens (INSPIRE), CBRF2-2023-00008

Ministry of the Environment, Conservation and Parks, https://ror.org/01q2d8e83, 2021-02-1-1564736554

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.29.667219v1

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Spatiotemporal #reconstruction of the North #American #H5N1 #outbreak reveals successive #lineage #replacements by descendant reassortants

Abstract

The November 2021 introduction of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b into North America triggered a devastating outbreak, affecting more than 180 million domestic birds and spreading to more than 80 wildlife species across Canada and the US. From this outbreak, we have sequenced 2955 complete A(H5N1) viral genomes from samples collected in Canada and, in conjunction with previously published data, performed multifaceted phylodynamic analyses. These analyses reveal extensive diversification of A(H5N1) viruses via reassortment with low-pathogenic avian influenza viruses. We find evidence of repeated ancestral strain replacement by direct descendants, indicative of compounding viral fitness increases. Spatiotemporal modeling identified critical geographic areas facilitating transcontinental spread and demonstrated genotype-specific host dynamics, offering essential data for ongoing control and prevention strategies.

Source: Science Advances, https://www.science.org/doi/10.1126/sciadv.adu4909

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Highly Pathogenic Avian #Influenza A(#H5N1) in Wild #Birds and a #Human, British Columbia, #Canada, 2024

Abstract

We characterized highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b genotype D1.1 in wild birds and a human in British Columbia, Canada, during 2024. D1.1, the predominant genotype circulating in fall 2024, is a reassortment between Eurasian A3 lineage viruses, introduced to North America in 2022, and North American lineage viruses.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/6/24-1862_article

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#Measles – Region of the #Americas (#WHO D.O.N., April 28 '25)

{Excerpt}

Situation at a glance

As of 18 April 2025, a total of 2318 measles cases, including three deaths, have been confirmed in six countries in the WHO Region of the Americas, an 11-fold increase compared to the same period in 2024. 

The majority of cases have occurred among people between 1 to 29 years, who are either unvaccinated or have an unknown vaccination status. 

Additionally, most cases are imported or linked to importation. 

Measles is a highly contagious, airborne viral disease that can lead to severe complications and death. 

Although it is preventable with two doses of the vaccine, over 22 million children worldwide did not receive their first dose of the vaccine in 2023. This has contributed to a global rise in measles cases in 2024, which heightens the risk of imported infections, particularly from unvaccinated travellers arriving from areas where the virus is actively circulating. 

WHO is working closely with countries in the WHO Region of the Americas to prevent the spread and reintroduction of measles. 

The regional risk is currently assessed as high, while the global risk remains moderate.

Description of the situation

From 1 January to 18 April 2025, a total of 2318 measles cases, including three deaths, were confirmed in the WHO Region of the Americas, an 11-fold increase compared to the 205 cases of measles reported in the same period in 2024. 

The cases have been reported from six countries: 

- Argentina (n= 21 cases), 

- Belize (n= 2 cases), 

- Brazil (n= 5 cases), 

- Canada (n=1069 cases), 

- Mexico (n= 421 cases including one death), and 

- the United States of America (n=800 cases, including two deaths).

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON565

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#Neuraminidase #reassortment and #oseltamivir #resistance in clade 2.3.4.4b A(#H5N1) viruses circulating among #Canadian #poultry, 2024

Abstract

We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada. Isolates from 8 farms reveal a mutation in the neuraminidase protein (H275Y) that is exceptionally rare among clade 2.3.4.4b viruses (present in 0.045% of publicly available clade 2.3.4.4b isolates). NA-H275Y is a well-known marker of resistance to the neuraminidase inhibitor oseltamivir. We demonstrate that this substitution maintains its resistance phenotype on the genetic background of H5N1 clade 2.3.4.4b viruses.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2469643

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#Canada - High pathogenicity avian #influenza #H5N5 viruses (#poultry) (Inf. with) - Immediate notification

On January 24, 2025, the Canadian Food Inspection Agency (CFIA) was notified of mortality in a non-commercial backyard layer poultry farm in Newfoundland and Labrador. The CFIA National Centre for Foreign Animal Disease has confirmed on February 12, 2025 that the virus was H5N5. The HA of the H5 virus from the samples belongs to Eurasian Gs/GD lineage HPAI H5N1 (2.3.4.4b) with cleavage site motif of “PLREKRRKR/GLF”, compatible with HPAI viruses. The sample contained AI virus similar to European like - H5N5 (2023) viruses which came to Canada via the Atlantic flyway. The viruses contained wholly Eurasian H5N5 genome segments. The CFIA has immediately quarantined the IP and is implementing strict movement controls and a stamping out policy. Primary control zone (PCZ) has been put in place around the IP. Surveillance is ongoing in the affected areas. WOAH data on poultry and non-poultry can be visualized and extracted on the AI dashboard in domestic birds available at https://cahss.ca/cahss-networks/poultry-new (select poultry categories to show data related to HPAI poultry events 4294, 5229, 6003, and 6267). Wildlife surveillance as well as the Canadian Notifiable Avian Influenza Surveillance System (CanNAISS) activities for poultry are ongoing in Canada.

Source: WOAH, https://wahis.woah.org/#/in-review/6267

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No #Evidence of Anti - #influenza #Nucleoprotein #Antibodies in Retail #Milk from Across #Canada (April to July 2024)

Abstract

Following reports of HPAI H5N1 infections of dairy cattle in the United States (US) in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies, as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the US has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.01.31.25321461v1

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Phylogeographic Characterizations of Recent (2015–2023) #Senecavirus A Isolates from #Canada

Abstract

Senecavirus A (SVA) continues to cause vesicular lesions in swine in Canada and many regions worldwide. Since the vesicular lesions caused by SVA are similar to those caused by foot and mouth disease virus, swine vesicular disease virus and vesicular stomatitis virus, a foreign animal disease investigation must be initiated to rule out these diseases. SVA isolates from pigs displaying vesicular lesions in Canada from 2015 to 2023 were sequenced, and phylogeographic analysis was performed using the complete genome sequences. The results infer that SVA has spread between the United States and Canada several times. In addition, the results suggest that SVA spreads from different regions. SVA spread was inferred from Canada into Thailand, India and Mexico and inferred from the United States to Brazil, Columbia, Chile and China with ten separate introductions. Furthermore, recombination was observed in SVA genomes from Canada, the United States and China.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/141

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#Critical #Illness in an #Adolescent with #Influenza A(#H5N1) Virus #Infection

To the Editor:

Highly pathogenic avian influenza A(H5N1) viruses are circulating among wild birds and poultry in British Columbia, Canada.1 These viruses are also recognized to cause illness in humans. Here, we report a case of critical illness caused by influenza A(H5N1) virus infection in British Columbia.

On November 4, 2024, a 13-year-old girl with a history of mild asthma and an elevated body-mass index (the weight in kilograms divided by the square of the height in meters) of greater than 35 presented to an emergency department in British Columbia with a 2-day history of conjunctivitis in both eyes and a 1-day history of fever. She was discharged home without treatment, but cough, vomiting, and diarrhea then developed, and she returned to the emergency department on November 7 in respiratory distress with hemodynamic instability. On November 8, she was transferred, while receiving bilevel positive airway pressure, to the pediatric intensive care unit at British Columbia Children’s Hospital with respiratory failure, pneumonia in the left lower lobe, acute kidney injury, thrombocytopenia, and leukopenia (...). A nasopharyngeal swab obtained at admission was positive for influenza A but negative for A(H1) and A(H3) by the BioFire Respiratory Panel 2.1 assay (BioFire Diagnostics). Reflex testing of the specimen with the Xpert Xpress CoV-2/Flu/RSV plus assay (Cepheid) revealed an influenza A cycle threshold (Ct) value of 27.1. This finding indicates a relatively high viral load for which subtyping would be expected; the lack of subtype identification suggested infection with a novel influenza A virus. Oseltamivir treatment was started on November 8 (Table S2), and the use of eye protection, N95 respirators, and other precautions against droplet, contact, and airborne transmission were implemented.

A reverse-transcriptase–polymerase-chain-reaction (RT-PCR) test specific for influenza A(H5)2 was positive on the day of admission. The patient had signs of respiratory deterioration — chest radiographs were consistent with progression to acute respiratory distress syndrome (...) — which prompted tracheal intubation and initiation of venovenous extracorporeal membrane oxygenation (ECMO) on November 9. Continuous renal replacement therapy was initiated on November 10. Combination antiviral treatment with amantadine (initiated on November 9) and baloxavir (initiated on November 11) was added to ongoing treatment with oseltamivir. Bacterial cultures of blood (samples obtained at admission) and endotracheal aspirate (obtained after intubation) yielded no growth.

Because of concern for cytokine-mediated hemodynamic instability, plasma exchange was performed daily from November 14 through November 16. Serial influenza A–specific RT-PCR tests showed increasing Ct values, which suggested a decline in the viral RNA load in serum and a decline in viral RNA in upper- and lower-respiratory specimens shortly after the initiation of antiviral treatment, with the first negative RT-PCR result for serum obtained on November 16 (...). It is notable that lower-respiratory specimens consistently yielded lower Ct values than upper-respiratory specimens, a finding that suggested higher viral levels in the lower-respiratory tract (...).

Influenza A(H5N1) virus was cultured from respiratory specimens obtained between November 8 and November 12 but not from subsequent respiratory specimens or from any serum specimens (...). No evidence of reduced susceptibility to any of the three antiviral agents used in treatment was observed in serial respiratory specimens by either genomic analysis or phenotypic testing with the NA-Star influenza neuraminidase inhibitor resistance detection kit (ThermoFisher Scientific) (...). The patient’s respiratory status improved, ECMO was discontinued on November 22, and the patient’s trachea was extubated on November 28.

The viral genome sequence obtained from a tracheal-aspirate specimen collected on November 9 (8 days after the onset of symptoms) was reconstructed as described previously.3 The virus was typed as clade 2.3.4.4b, genotype D1.1,4 most closely related to viruses detected in wild birds in British Columbia around the same time (...). Markers of adaptation to humans were detected in the tracheal-aspirate specimen collected on November 9: the E627K mutation was detected (52% allele frequency) in the polymerase basic 2 (PB2) gene product, and analysis of the H5 hemagglutinin (HA) gene yielded ambiguous calls in the codons for amino acid residues E186 (E190 according to H3 mature HA numbering) — 28% allele frequency for E186D — and Q222 (Q226 according to H3 mature HA numbering) — 35% allele frequency for Q222H. The mutations in the H5 HA gene have previously been shown to increase binding to α2-6–linked sialic acids, which act as receptors that facilitate viral entry into cells in the human respiratory tract and enable viral replication.5

Highly pathogenic avian influenza A(H5N1) virus infection acquired in North America can cause severe human illness. Evidence for changes to HA that may increase binding to human airway receptors is worrisome.

Agatha N. Jassem, Ph.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Ashley Roberts, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada; John Tyson, Ph.D., James E.A. Zlosnik, Ph.D., Shannon L. Russell, Ph.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Jessica M. Caleta, M.Sc., Public Health Agency of Canada, Winnipeg, MB, Canada; Eric J. Eckbo, M.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Ruimin Gao, Ph.D., Taeyo Chestley, Ph.D., Public Health Agency of Canada, Winnipeg, MB, Canada; Jennifer Grant, M.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Timothy M. Uyeki, M.D., M.P.H., Centers for Disease Control and Prevention, Atlanta, GA; Natalie A. Prystajecky, Ph.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Chelsea G. Himsworth, D.V.M., Ph.D., British Columbia Ministry of Agriculture and Food, Abbotsford, BC, Canada; Elspeth MacBain, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada; Charlene Ranadheera, Ph.D., Public Health Agency of Canada, Winnipeg, MB, Canada; Lynne Li, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada; Linda M.N. Hoang, M.D., British Columbia Centre for Disease Control, Vancouver, BC, Canada; Nathalie Bastien, Ph.D., Public Health Agency of Canada, Winnipeg, MB, Canada; David M. Goldfarb, M.D., British Columbia Children’s Hospital, Vancouver, BC, Canada.

Source: New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMc2415890

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Recurring #incursions and #dissemination of novel #Eurasian-origin #H5Nx avian #influenza viruses in Atlantic #Canada

Abstract

Wild birds are important hosts of influenza A viruses (IAVs) and play an important role in their ecology. The emergence of the A/goose/Guangdong/1/1996 H5N1 (Gs/GD) lineage marked a shift in IAV ecology, leading to recurrent outbreaks and mortality in wild birds from 2002 onwards. This lineage has evolved and diversified over time, with a recent important derivative being the 2.3.4.4b sub-lineage, which has caused significant mortality events in wild bird populations. An H5N1 clade 2.3.4.4b virus was transmitted into North America from Eurasia in 2021, with the first detection being in Newfoundland and Labrador in Atlantic Canada, and this virus and its reassortants then spread broadly throughout North America and beyond. Following the first 2021 detection, there have been three additional known incursions of Eurasian-origin strains into Atlantic Canada, a second H5N1 strain in 2022 and two H5N5 strains in 2023. In this study, we document a fifth incursion in Atlantic Canada that occurred in 2023 by another H5N5 strain. This strain spread throughout Atlantic Canada and into Quebec, infecting numerous species of wild birds and mammals. Genomic analysis revealed mammalian-adaptive mutations in some of the detected viruses (PB2-E627K and PB2-D701N) and mutations in the hemagglutinin (HA) and neuraminidase (NA) genes that are associated with enhanced viral fitness and avian transmission capabilities. Our findings indicate that this virus is continuing to circulate in wildlife, and confirms Atlantic Canada is an important North American entry point for Eurasian IAVs. Continued surveillance and genomic analysis of IAVs detected in the region is crucial to monitor the evolution of these viruses and assess potential risks to wildlife and public health.

Source: Virus Evolution, https://academic.oup.com/ve/article/10/1/veae111/7926332

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Intensive #transmission in wild, migratory #birds drove rapid geographic #dissemination and repeated #spillovers of #H5N1 into #agriculture in North #America

Abstract

Since late 2021, a panzootic of highly pathogenic H5N1 avian influenza virus has driven significant morbidity and mortality in wild birds, domestic poultry, and mammals. In North America, infections in novel avian and mammalian species suggest the potential for changing ecology and establishment of new animal reservoirs. Outbreaks among domestic birds have persisted despite aggressive culling, necessitating a re-examination of how these outbreaks were sparked and maintained. To recover how these viruses were introduced and disseminated in North America, we analyzed 1,818 Hemagglutinin (HA) gene sequences sampled from North American wild birds, domestic birds and mammals from November 2021-September 2023 using Bayesian phylodynamic approaches. Using HA, we infer that the North American panzootic was driven by ~8 independent introductions into North America via the Atlantic and Pacific Flyways, followed by rapid dissemination westward via wild, migratory birds. Transmission was primarily driven by Anseriformes, shorebirds, and Galliformes, while species such as songbirds, raptors, and owls mostly acted as dead-end hosts. Unlike the epizootic of 2015, outbreaks in domestic birds were driven by ~46-113 independent introductions from wild birds, with some onward transmission. Backyard birds were infected ~10 days earlier on average than birds in commercial poultry production settings, suggesting that they could act as early warning signals for transmission upticks in a given area. Our findings support wild birds as an emerging reservoir for HPAI transmission in North America and suggest continuous surveillance of wild Anseriformes and shorebirds as crucial for outbreak inference. Future prevention of agricultural outbreaks may require investment in strategies that reduce transmission at the wild bird/agriculture interface, and investigation of backyard birds as putative early warning signs.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.16.628739v1

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