Sunday, February 9, 2025

Limited #transmission of avian #influenza viruses, #avulaviruses, #coronaviruses and #Chlamydia sp. at the interface between wild #birds and a free-range duck #farm

Abstract

Recent outbreaks of highly pathogenic avian influenza in Europe have raised questions regarding the epidemiological role of commensal wild birds on free-range poultry farms. This study aimed to assess the prevalence of avian influenza viruses (AIV), avulaviruses, coronaviruses and Chlamydia sp. in commensal wild birds on a free-range duck farm in southwestern France and to evaluate possible transmission events at the wild‒domestic interface. From 2019 through 2021, a longitudinal study was conducted on wild birds, domestic ducks and their shared environment on farms. Commensal wild birds were captured and sampled for blood and swabs, and fresh feces from cattle egrets visiting the farm were collected. In parallel, domestic ducks were sampled, and environmental samples were collected. The presence of the four pathogens was tested by q(RT-)PCR, and the immunity of wild birds to AIV and Newcastle disease virus (NDV) was tested by ELISA. Wild birds were found to shed AIV and Chlamydia only, with a low prevalence (< 3%). The seroprevalence rates were less than 10% for AIV and less than 4.5% for NDV. No significant temporal trend was identified. Ducks and their environment frequently test simultaneously positive for the same pathogens (19 to 44% of flocks), mostly during fall‒winter. In addition to unrelated temporal patterns, the identification of pathogens in wild birds seemed unrelated to that in domestic ducks. These results suggest a low transmissibility of the avian pathogens tested in our study at the wild‒domestic interface and highlight the limited contribution of commensal wild birds in comparison with free-range poultry to the global microbiological pressure on the environment.

Source: Veterinary Research, https://veterinaryresearch.biomedcentral.com/articles/10.1186/s13567-025-01466-3

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#Pathology of #Influenza A (#H5N1) #infection in #pinnipeds reveals novel tissue #tropism and vertical #transmission.

Abstract

In 2023, an unprecedented outbreak of highly pathogenic avian influenza (HPAI) H5N1 resulted in the death of thousands of pinnipeds along the Argentinean coast, raising concerns about its ecological and epidemiological impact. Here, we present clinical, pathological, and molecular findings associated with HPAI H5N1 infection in pinnipeds from Chubut, Argentina. Necropsies were conducted on three South American Sea Lions (SASLs) (Otaria flavescens) and one Southern Elephant Seal (SES) (Mirounga leonina), followed by histopathological, immunohistochemical and RT-sqPCR analyses. Neurological clinical signs were observed in two SASLs, with one also exhibiting respiratory distress. Neuropathological findings included lymphoneutrophilic meningoencephalomyelitis and choroiditis, neuronal necrosis, gliosis, hemorrhages, and perivascular cuffing. Viral antigen was localized in neurons, glial cells, choroid plexus epithelial cells, ependymal cells, and the neuropil. Systemic manifestations included HPAI-related necrotizing myocarditis in the elephant seal and placental necrosis in a sea lion, with fetal tissues testing positive for HPAIV. Pulmonary lesions were minimal, limited to bronchial glands in one individual. RT-sqPCR confirmed HPAI H5 in all tested animals. Our findings highlight the neurotropism of HPAI H5N1 in pinnipeds, and expand the known systemic effects of the virus, revealing new tissue tropism and vertical transmission.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.07.636856v1

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{#USA, #Nevada} The Occurrence of Another Highly Pathogenic Avian #Influenza (HPAI) #Spillover from Wild #Birds into Dairy #Cattle

Background  

In March 2024, the USDA confirmed the first case of highly pathogenic avian influenza (HPAI) spreading between dairy cattle herds in the United States. 

This followed reports from dairy producers of an unusual illness in their lactating cows over the preceding 2-3 months. 

Virus whole genome sequencing and modeling performed by USDA suggested a single spillover of HPAI H5N1, clade 2.3.4.4b, genotype B3.13 from wild birds into dairy cattle likely occurred between October 2023 and January 2024 (1). 

Since then, federal, state, and industry partners have collaborated to address the HPAI threat in dairy cattle, resulting in two federal orders and the implementation of the National Milk Testing Strategy (NMTS). 

States began enrolling in the NMTS in December 2024, in which they are continuing to conduct or now implementing state-wide bulk tank surveillance and/or milk processing plant silo monitoring. 

Nevada was among the first to participate in the National Silo Monitoring Program, which includes testing milk samples from processing plant silos for HPAI. 

This sampling scheme coincides with the FDA's existing regulatory program, which requires all raw milk Grade A silos to be sampled four times within 6 months. 

The Detection In Nevada, 3 of 11 silo samples collected on January 6 and 7, 2025 tested positive for HPAI via polymerase chain reaction (PCR) at the National Veterinary Services Laboratories (NVSL) on January 10. 

The state was notified, triggering an investigation to trace the source, as up to  12 dairies (in the same geographic region) could have contributed milk to the affected silos. 

On January 17, regulatory officials collected on-farm bulk milk samples from suspected dairy farms and submitted them to the Washington Animal Disease Diagnostic Laboratory (WADDL), a member of the National Animal Health Laboratory Network (NAHLN). 

HPAI was confirmed via PCR at NVSL on Friday, January 24, in samples from two of those dairies. 

NVSL completed whole genome sequencing on January 31 and identified HPAI H5N1, clade 2.3.4.4b, genotype D1.1 in samples from four different bulk tanks from one herd. 

A second herd also showed a partial sequence consistent with D1.1. 

Clinical signs were not observed in the cattle prior to the detection, but have been reported since, and the affected dairy producers reported large wild bird die-offs near the dairies. 

While genotype D1.1 has been the dominant strain circulating in migratory wild birds across all four North American flyways during the winter of 2024-2025, these Nevada cases represent the f irst detection of a genotype other than B3.13 in U.S. dairy cattle and the second known spillover from wild birds into lactating dairy cattle. 


Virus Epidemiology and Origin 

Since late 2021, six separate introductions of Eurasian HPAI H5N1 clade 2.3.4.4b have been documented into the migratory wild birds in the North American flyways (genotypes A1 through A6). 

Genotype D1.1 is a reassortant of A3. Genotype A3 first appeared in the Pacific flyway in April of 2022 with detections only in the Pacific flyway until the fall of 2024. 

Since this fall, genotype A3 has been sporadically reported in migratory wild birds across all four flyways through wild bird surveillance, making up 3.3% of the overall detections to date. 

Genotype D1.1 retains four genes from the original A3 genotype; hemagglutinin (HA), polymerase basic 1 (PB1), matrix (M) and nonstructural (NS), with other genes originating from other North American lineage viruses found in migratory wild birds. 

This genotype was first detected in September 2024 and has quickly expanded to all North American flyways. 

D1.1 is the current predominant genotype in migratory wild birds, making up 6.07% of the total detections since 2022 despite f irst occurring late 2024. 

The D1.1 viruses identified in dairy cattle in Nevada were found to be closely related to other D1.1 viruses recently detected in migratory wild birds across multiple North American Flyways. 

Analysis of the hemagglutinin gene of the Nevada dairy cattle viruses did not identify changes predicted to impact infectivity or adaptation to mammalian hosts

However, a change of PB2 D701N commonly associated with mammalian adaptation of HPAI virus was identified in viruses sequenced from four separate dairy cattle. 

To date, this change has not been observed in D1.1 viruses found in wild birds or poultry and is not found in B3.13 genotype viruses detected in dairy cattle. 

PB2 D701N has previously been associated with mammalian adaptation because it improves RNA polymerase activity and replication efficiency in mammalian cells and has the potential to impact pathogenesis in infected mammals (2,3,4,5,6). 

The change has previously been identified in human cases of HPAI H5 but with no evidence of onward transmission among humans (7,8). 

No other changes associated with mammalian adaptation were identified in the sequences. 

Of note, these D1.1 viruses sequenced from dairy cattle do not contain the PB2 631L marker that appeared to be fixed in dairy cattle B3.13 sequences. 

Following the existing public sharing process, NVSL immediately provided the D1.1 sequence information the Centers for Disease Control and Prevention and will post sequence files to the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) within 7 days of analysis, adding metadata as sequences are interpreted and quality checked in light of epidemiological information.   


Summary 

This detection indicates that this HPAI virus, genotype D1.1, is the second spillover event from migratory wild birds to dairy cattle following the B3.13 event in late 2023/early 2024. 

Investigations are ongoing to fully characterize this event. The Nevada Department of Agriculture acted quickly, by first rapidly enrolling in the NMTS to initiate active surveillance, and then to identify and quarantine the affected dairies before cattle movements could further transmit this virus beyond the local area. 

This is the first instance where sampling of milk at processing plants rather than individually or directly on farm has detected a high consequence disease, demonstrating silo monitoring as an efficient method to monitor HPAI in the National dairy herd.  


1. Nguyen T, Hutter C, Markin A, Thomas M, Lantz K, Killian M, Janzen GM, Vijendran S, Wagle S, Inderski B, Magstadt DR, Li G, Diel DG, Frye EA, Dimitrov SM, Swinford A, Thompson AC, Snevik KR, Suarez DL, Spackman E, Lakin S, Ahola SC, Johnson SR, Baker A, Robbe-Austerman S, Torchetti M, Anderson TK. 2024. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle. bioRxiv 2024.05.01.591751; doi: https://doi.org/10.1101/2024.05.01.591751 

2. Li Z, Chen H, Jiao P, Deng G, Tian G, Li Y, Hoffmann E, Webster RG, Matsuoka Y, Yu K. 2005. Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. The Journal of Virology 79:12058-12064. 

3. Gabriel G, Abram M, Keiner B, Wagner R, Klenk HD, Stech J. 2007. Differential polymerase activity in avian and mammalian cells determines host range of influenza virus. J Virol 81:9601-4. 

4. Steel J, Lowen AC, Mubareka S, Palese P. 2009. Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog 5:e1000252. 

5. Gao Y, Zhang Y, Shinya K, Deng G, Jiang Y, Li Z, Guan Y, Tian G, Li Y, Shi J, Liu L, Zeng X, Bu Z, Xia X, Kawaoka Y, Chen H. 2009. Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoSPathog 5:e1000709. 

6. Zhou B, Pearce MB, Li Y, Wang J, Mason RJ, Tumpey TM, Wentworth DE. 2013. Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus. PLoS ONE 8:e67616. 

7. Le QM, Ito M, Muramoto Y, Hoang PV, Vuong CD, Sakai-Tagawa Y, Kiso M, Ozawa M, Takano R, Kawaoka Y. 2010. Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam. J Gen Virol 91:2485-90.  

8. Zhu W, Li X, Dong J, Bo H, Liu J, Yang J, Zhang Y, Wei H, Huang W, Zhao X, Chen T, Yang J, Li Z, Zeng X, Li C, Tang J, Xin L, Gao R, Liu L, Tan M, Shu Y, Yang L, Wang D. 2022. Epidemiologic, Clinical, and Genetic Characteristics of Human Infections with Influenza A(H5N6) Viruses, China. Emerg Infect Dis 28:1332-1344. 

Source: US Department of Health, https://www.aphis.usda.gov/sites/default/files/dairy-cattle-hpai-tech-brief.pdf

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Friday, February 7, 2025

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {Jan. 7 '25)



 {Excerpt}

Time Period: January 26 - February 01, 2025

-- H5 Detection: 17 sites (4.9%)

-- No Detection: 331 sites (95.1%)

-- No samples in last week: 51 sites

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html
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#USA, One #human infection with #H1N2 #variant #influenza virus has been reported by #Iowa

{Excerpt}

Novel Influenza A Virus Infections

One human infection with influenza A(H1N2) variant (A(H1N2)v) virus was reported by the Iowa Department of Health and Human Services.

The patient is ≥18 years of age and sought health care during the week ending January 18, 2025 (Week 3), was hospitalized, and has recovered from their illness. 

An investigation by state public health officials did not identify direct or indirect swine contact by the patent. 

No illness was identified among the patient's close contacts. 

No human-to-human transmission has been identified associated with this case.

This is the first human infection with a variant influenza virus reported during the 2024-2025 season in the United States.

When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a "variant" influenza virus. 

Most human infections with variant influenza viruses occur following exposure to swine, but human-to-human transmission can occur. 

It is important to note that in most cases, variant influenza viruses have not shown the ability to spread easily and sustainably from person to person. 

Additional information on influenza in swine, variant influenza virus infection in humans, and guidance to interact safely with swine can be found at www.cdc.gov/flu/swineflu/index.htm.

No new human infections with A(H5) were reported to CDC this week. An ongoing outbreak of H5N1 continues in domestic dairy cows and poultry, and monitoring for additional human cases is ongoing.

The CSTE position statement, which includes updated case definitions for confirmed, probable, and suspected cases is available at http://www.cste.org/resource/resmgr/position_statements_files_2023/24-ID-09_Novel_Influenza_A.pdf

An up-to-date human A(H5) case summary during the outbreak by state and exposure source is available at www.cdc.gov/bird-flu/situation-summary/index.html

Information about avian influenza is available at https://www.cdc.gov/flu/avianflu/index.htm.

Interim recommendations for Prevention, Monitoring, and Public Health Investigations are available at https://www.cdc.gov/bird-flu/prevention/hpai-interim-recommendations.html.

The latest case reports on avian influenza outbreaks in wild birds, commercial poultry, backyard or hobbyist flocks, and mammals in the United States are available from the USDA at https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/animal-disease-information/avian/avian-influenza/2022-hpai.

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Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/fluview/surveillance/2025-week-05.html

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#USA, After #Birdflu Detected in Local #Cat, County #Health Officials Say #Pet Owners Should Contact Veterinarian When Their Pets are Sick

Redwood City — State veterinary and health officials have confirmed a case of H5N1 (bird flu) in a domestic stray cat in San Mateo County. 

The infection, which is not related to the recent instance of bird flu in a backyard flock, was found in a stray cat in Half Moon Bay that had been taken in by a family

When it showed symptoms, they took it to Peninsula Humane Society, whose veterinarians examined it and requested testing. Lab results confirmed H5N1. 

It is not known how the cat was infected and it was euthanized due to its condition.

Cats may be exposed to bird flu by consuming infected bird, being in environments contaminated with the virus and consuming unpasteurized milk from infected cows or raw food. Inside domestic animals, such as cats and dogs, that go outside are also at risk of infection.​​​​​​​

According to the Centers for Disease Control and Prevention, the risk of cats spreading H5N1 to people is extremely low, though it is possible for cats to spread some strains of bird flu to people.

While there are no human cases of H5N1 related to this case, this detection in a cat highlights the importance of being proactive about preventing the spread of the virus.

Residents whose pets show signs of illness should contact their veterinarian.

Pets infected with H5N1 may experience a loss of appetite, lethargy and fever, along with neurologic signs, including circling, tremors, seizures or blindness. The illness may quickly progress to:

-- Severe depression

-- Discharge from eyes or nose

-- Other respiratory signs, such as rapid shallow breathing, difficulty breathing and sneezing or coughing

-- Pets with severe illness may die.

If a pet is showing signs of illness consistent with bird flu and has been exposed to infected (sick or dead) wild birds or poultry, residents should contact a veterinarian and monitor their own health for signs of fever or infection.

“We all want to make sure our companion animals are healthy and safe from disease,” said Lori Morton-Feazell, San Mateo County’s chief of Animal Control and Licensing. “If your pet is sick, your veterinarian can determine whether it should be tested for bird flu or any other virus or disease.”

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Source: County of San Mateo, https://www.smcgov.org/ceo/news/after-bird-flu-detected-local-cat-county-health-officials-say-pet-owners-should-contact

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Thursday, February 6, 2025

Highly Pathogenic Avian #Influenza Virus #H5N1 in Double-crested #Cormorants (Nannopterum auritum) of the #Chesapeake Bay, #USA

Abstract

Double-crested Cormorants (Nannopterum auritum) have historically exhibited low levels of infection and antibodies to avian influenza virus (AIV). The recent global expansion of clade 2.3.4.4b A/goose/Guangdong/1/1996 highly pathogenic (HP) avian influenza virus H5N1 (HPAI H5N1) has resulted in large-scale mortalities across diverse waterbird taxa including cormorants. We sampled 32 and 29 Double-crested Cormorants breeding in the Chesapeake Bay, US, during the summers of 2023 and 2024, respectively, to assess HPAI H5N1 infection and AIV antibodies. Although no mortality was observed in the area, one bird sampled in 2023 was infected with HPAI H5N1. Additionally, 21/31 individuals in 2023 and 10/25 individuals in 2024 for which sera were collected had AIV antibodies. Based on additional testing using hemagglutination inhibition, virus neutralization, and an enzyme-linked lectin assay, 94 and 100% (2023 and 2024, respectively) of the seropositive birds tested positive for antibodies to both H5 and N1, suggesting previous infection with HPAI H5N1. These results are consistent with survival and limited clinical effects related to HPAI H5N1 infections. Furthermore, these results suggest that population immunity to HPAI H5N1 within the Chesapeake Bay might reduce future infections and potential population impacts should HP H5N1 remain on the landscape, though immunity may be waning across time. Because results are based on a single population, additional testing for both infection and antibodies as well as continued monitoring could enhance understanding of antibody persistence.

Source: US National Library of Medicine, https://pubmed.ncbi.nlm.nih.gov/39911059/

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Emergence of a Novel #Reassortant Clade 2.3.2.1c Avian #Influenza A #H5N1 Virus Associated with #Human Cases in #Cambodia

Abstract

After nearly a decade without reported human A/H5N1 infections, Cambodia faced a sudden resurgence with 16 cases between February 2023 and August 2024, all caused by A/H5 clade 2.3.2.1c viruses. Fourteen cases involved a novel reassortant A/H5N1 virus with gene segments from both clade 2.3.2.1c and clade 2.3.4.4b viruses. The emergence of this novel genotype underscores the persistent and ongoing threat of avian influenza in Southeast Asia. This study details the timeline and genomic epidemiology of these infections and related poultry outbreaks in Cambodia.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.11.04.24313747v2

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

 One Cygnus species wild bird in Sachsen Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6245

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Viral #kinetics of #H5N1 #infections in dairy #cattle

Abstract

Since early-2024 unprecedented outbreaks of highly pathogenic avian influenza H5N1 clade 2.3.4.4b have been ongoing in dairy cattle in the United States with significant consequences for the dairy industry and public health. Estimation of key epidemiological parameters is required to support outbreak response, including predicting the likely effectiveness of interventions and testing strategies. Here we pool limited publicly available data from three studies of naturally and experimentally infected dairy cattle. We quantify Ct value trajectories of infected dairy cattle and the relationship between Ct value and the log-titre of infectious virus, a proxy for infectiousness. We estimate that following infection peak Ct values are rapidly reached within 1--2 days with a population mean Ct value of 16.9 (13.2, 20.5). We identify a critical threshold Ct value of 21.5 (20.1, 23.6), with values of Ct value above this threshold representing little-to-no infectious viral load. Finally, we estimate the distribution of the duration of infectiousness for dairy cattle (i.e. the duration their Ct value remains above the critical threshold) with a population median of 6.2 (2.8, 13.1) days.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.01.636082v1

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Wednesday, February 5, 2025

#USA, APHIS Confirms {Avian #Influenza #H5N1} #D11 #Genotype in Dairy #Cattle in #Nevada

On January 31, 2025, the USDA Animal and Plant Health Inspection Service (APHIS) National Veterinary Services Laboratories (NVSL) confirmed by whole genome sequence the first detection of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b, genotype D1.1 in dairy cattle

This confirmation was a result of State tracing and investigation, following an initial detection on silo testing under the USDA’s National Milk Testing Strategy (NMTS) in Nevada. 

USDA APHIS continues to work with the Nevada Department of Agriculture by conducting additional on-farm investigation, testing, and gathering additional epidemiological information to better understand this detection and limit further disease spread. 

This is the first detection of this virus genotype in dairy cattle (all previous detections in dairy cattle have been HPAI H5N1 clade 2.3.4.4b, genotype B3.13). 

Genotype D1.1 represents the predominant genotype in the North American flyways this past fall and winter and has been identified in wild birds, mammals, and spillovers into domestic poultry

The detection does not change USDA’s HPAI eradication strategy and is a testament to the strength of our National Milk Testing Strategy (NTMS). In the interest of sharing information of import to the scientific community, APHIS will publish a technical brief on the findings on our website and post the sequence data on GenBank in the coming week. 

Source: Department of Agriculture, https://www.aphis.usda.gov/news/program-update/aphis-confirms-d11-genotype-dairy-cattle-nevada-0

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Differential #protection against #SARS-CoV-2 #reinfection pre- and post- #Omicron

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved over short timescales, leading to the emergence of more transmissible variants such as Alpha and Delta. The arrival of the Omicron variant marked a major shift, introducing numerous extra mutations in the spike gene compared with earlier variants. These evolutionary changes have raised concerns regarding their potential impact on immune evasion, disease severity and the effectiveness of vaccines and treatments. In this epidemiological study, we identified two distinct patterns in the protective effect of natural infection against reinfection in the Omicron versus pre-Omicron eras. Before Omicron, natural infection provided strong and durable protection against reinfection, with minimal waning over time. However, during the Omicron era, protection was robust only for those recently infected, declining rapidly over time and diminishing within a year. These results demonstrate that SARS-CoV-2 immune protection is shaped by a dynamic interaction between host immunity and viral evolution, leading to contrasting reinfection patterns before and after Omicron’s first wave. This shift in patterns suggests a change in evolutionary pressures, with intrinsic transmissibility driving adaptation pre-Omicron and immune escape becoming dominant post-Omicron, underscoring the need for periodic vaccine updates to sustain immunity.

Source: Nature, https://www.nature.com/articles/s41586-024-08511-9

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

 A wild Barnacle Goose in Rogaland Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6244

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#Italy - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (a domestic #cat) (2017-) - Immediate notification

The Database of Global Administrative Boundaries (GADM) used by WAHIS, provides Crespellano as the municipality corresponding to the given coordinates. As a matter of fact the location of the infected premises is the municipality of Valsamoggia Domestic cat found dead on 13 January 2025 at a family poultry farm located in the municipality of Valsamoggia (BO). As expected, the virus has the highest genetic similarity to the H5N1 virus sequenced from poultry from the same farm that tested positive on December 31st. These results confirm that the cat likely became infected following direct exposure to infected poultry at the same site where it was found dead.

Source: WOAH, https://wahis.woah.org/#/in-review/6243

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#KP2 - based monovalent #mRNA #vaccines robustly boost #antibody responses to #SARS-CoV-2

{Excerpt}

In response to the ongoing evolution of SARS-CoV-2, vaccine manufacturers have released updated COVID-19 vaccines annually since 2022. For much of 2024, the global spread was dominated by the JN.1 lineage of viruses,1 which are antigenically quite distant from the XBB.1.5 variant that was used in the previous vaccine booster.2 In August 2024, the US Food and Drug Administration authorised two updated mRNA vaccines (Pfizer–BioNTech and Moderna) based on the spike sequence of KP.2, a subvariant in the JN.1 lineage.3 In the UK and the EU, a KP.2-based mRNA vaccine (BioNTech) was also authorised later in the year.4,5 We have now provided the first indication of the acute boosting effect of updated KP.2 monovalent mRNA vaccines (KP.2 MV) on serum SARS-CoV-2 neutralising antibodies in humans. Since the authorisation of the updated vaccine boosters, SARS-CoV-2 has evolved beyond KP.2, with the subvariant KP.3.1.1 becoming dominant globally and the subvariant XEC now gaining traction rapidly.1 KP.2 contains Arg346Thr, Phe456Leu, and Val1104Leu mutations in spike, in addition to those present in the parental JN.1 (figure A). Both KP.3.1.1 and XEC share Phe456Leu and Val1104Leu mutations found in KP.2, along with Gln493Glu, which is absent in KP.2. In addition, KP.3.1.1 harbors the Ser31del mutation, whereas XEC carries Thr22Asn and Phe59Ser mutations; neither KP.3.1.1 nor XEC possess the Arg346Thr mutation (figure A). The effectiveness of the updated KP.2 MV boosters on neutralising antibodies in human serum against recently dominant subvariants has yet to be reported.

(...)

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00058-1/fulltext?rss=yes

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Tuesday, February 4, 2025

Modeling suggests #SARS-CoV-2 #rebound after #nirmatrelvir-ritonavir #treatment is driven by target cell preservation coupled with incomplete viral clearance

ABSTRACT

In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of N-R near the time of symptom onset, coupled with incomplete viral clearance, appears to be the main factor leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by the time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. A comparison with an untreated cohort suggests that early treatments with nirmatrelvir-ritonavir may be associated with a delay in the onset of an adaptive immune response. Nevertheless, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment to a 10-day regimen may greatly diminish the chance of rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01623-24?af=R

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Highly pathogenic avian #influenza virus (#H5N5) detected in an Atlantic #walrus (Odobenus rosmarus rosmarus) in the #Svalbard Archipelago, #Norway, 2023

ABSTRACT

We present the first documented case of highly pathogenic avian influenza virus (HPAIV) subtype H5N5 in an Atlantic walrus (Odobenus rosmarus rosmarus). The animal was found dead in Svalbard, Norway, in 2023. Sequence analysis revealed the highest genetic similarity with virus isolates from different avian hosts.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2456146

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#Japan - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 Three wild Hooded Cranes in Izumi Region, Kagoshima city.

Source: WOAH, https://wahis.woah.org/#/in-review/6239

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Groundbreaking #Ebola #vaccination #trial launches today in #Uganda

{Excerpt}

In a global first, Uganda’s Ministry of Health, the World Health Organization (WHO) and other partners today launched a first ever vaccine trial for Ebola from the Sudan species of the virus, and at an unprecedented speed for a randomized vaccine trial in an emergency.

The principal investigators from Makerere University and the Uganda Virus Research Institute (UVRI), with support from WHO and other partners, have worked tirelessly to get the trial ready in 4 days since the outbreak was confirmed on 30 January. It is the first trial to assess the clinical efficacy of a vaccine against Ebola disease due to Sudan virus. The speed was achieved through advanced research preparedness, while ensuring full compliance with national and international regulatory and ethical requirements.

The candidate vaccine was donated by IAVI, with financial support from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), Canada’s International Development Research Centre (IDRC), and the European Commission's Health Emergency Preparedness and Response Authority (HERA) and support from the Africa Centres for Disease Control and Prevention (Africa CDC).

“This is a critical achievement towards better pandemic preparedness, and saving lives when outbreaks occur,” said Dr Tedros Adhanom Ghebreyesus, WHO’s Director-General.  

“This is possible because of the dedication of Uganda’s health workers, the involvement of communities, the Ministry of Health of Uganda, Makerere University and UVRI, and research efforts led by WHO involving hundreds of scientists through our research and development Filoviruses network. We thank our partners for their dedication and cooperation, from IAVI for donating the vaccine, to CEPI, EU HERA and Canada’s IDRC for funding, and Africa CDC for further support. This massive achievement would simply not be possible without them.”

In 2022, during the previous outbreak of Ebola disease (also from the Sudan species of the virus) in Uganda, a randomized protocol for candidate vaccines was developed. Principal investigators were designated under the leadership of the Minister of Health, and teams were trained to allow such a trial to take place during an active outbreak.

The randomized vaccine trial to assess the recombinant vesicular stomatitis virus (rVSV) candidate vaccine was launched at a ceremony in Kampala today by the Minister of Health of Uganda. WHO is co-sponsoring the trial. WHO was represented by Dr Mike Ryan, Executive Director of WHO’s Health Emergencies Programme and Deputy Director-General, and the WHO representative to Uganda Dr Kasonde Mwinga, along with other colleagues.

Three vaccination rings were defined today. The first ring involves about 40 contacts and contacts of contacts of the first reported and confirmed case, a health worker who has died.

Although several promising candidate medical countermeasures are progressing through clinical development, as of now, there is no licensed vaccine available to effectively combat a potential future outbreak of Ebola disease from the Sudan species of the virus. Licensed vaccines exist only for the disease caused by Ebola virus, formerly known as ZaĂ¯re ebolavirus. Likewise for treatments, approved treatments are only available for Ebola virus.

The vaccine for the trial was recommended by the independent WHO candidate vaccine prioritization working group. If the candidate vaccine is effective, it can contribute to controlling this outbreak and generate data for vaccine licensure.

In 2022, the research teams were trained in good clinical practice (GCP) and standard operating procedures for such trials. They completed refresher training in recent days. WHO colleagues experienced in trials and in ring vaccination arrived in Uganda over the weekend to support the trial implementation and GCP compliance.

The vaccine doses were pre-positioned in the country. WHO worked with the principal investigators and national authorities and the vaccine developer to review cold chain documentation and ensure the doses were stored correctly over the previous years. As part of the signed agreement with the Ministry of Health, WHO has a signed agreement with IAVI for additional doses of the candidate vaccine to be made available shortly.

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Source: World Health Organization, https://www.who.int/news/item/03-02-2025-groundbreaking-ebola-vaccination-trial-launches-today-in-uganda

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Development of avian #influenza A(#H5) virus #datasets for #Nextclade enables rapid and accurate clade assignment

Abstract

The ongoing panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses is the largest in history, with unprecedented transmission to multiple mammalian species. Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their hemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response. Co-circulation of endemic, low pathogenic avian influenza (LPAI) A(H5) lineages in North American and European wild birds necessitates the ability to rapidly and accurately distinguish between infections arising from these lineages and epizootic HPAI A(H5) viruses. However, currently available clade assignment tools are limited and often require command line expertise, hindering their utility for public health surveillance labs. To address this gap, we have developed datasets to enable A(H5) clade assignments with Nextclade, a drag-and-drop tool originally developed for SARS-CoV-2 genetic clade classification. Using annotated reference datasets for all historical A(H5) clades, clade 2.3.2.1 descendants, and clade 2.3.4.4 descendants provided by the Food and Agriculture Organization/World Health Organization/World Organisation for Animal Health (FAO/WHO/WOAH) H5 Working Group, we identified clade-defining mutations for every established clade to enable tree-based clade assignment. We then created three Nextclade datasets which can be used to assign clades to A(H5) HA sequences and call mutations relative to reference strains through a drag-and-drop interface. Nextclade assignments were benchmarked with 19,834 unique sequences not in the reference set using a pre-released version of LABEL, a well-validated and widely used command line software. Prospective assignment of new sequences with Nextclade and LABEL produced very well-matched assignments (match rates of 97.8% and 99.1% for the 2.3.2.1 and 2.3.4.4 datasets, respectively). The all-clades dataset also performed well (94.8% match rate) and correctly distinguished between all HPAI and LPAI strains. This tool additionally allows for the identification of polybasic cleavage site sequences and potential N-linked glycosylation sites. These datasets therefore provide an alternative, rapid method to accurately assign clades to new A(H5) HA sequences, with the benefit of an easy-to-use browser interface.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.07.631789v2

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