Spatio-temporal #dynamics and #risk cluster #analysis of highly pathogenic avian #influenza (#H5N1) in #poultry: Advancing #outbreak #management through customized regional strategies in #Egypt

ABSTRACT 

Background: 

Highly pathogenic avian influenza (HPAI) (H5N1) has been endemic in Egypt for almost two decades, profoundly impacting both the poultry industry and public health. Egypt stands as a prominent epicenter for HPAI H5N1 outbreaks in Africa, marked by the highest number of positive human cases. Despite continuous governmental efforts, prior research underscored the inadequacy of strategies in controlling the virus spread. 

Aim: 

This study identified spatiotemporal patterns and high-risk clusters of HPAI H5N1 outbreaks at the subdistrict level. 

Methods: 

This study involved trial tracking of HPAI H5N1 endemicity dynamics, enabling tailored interventions at a regional level based on robust epidemiological investigations to address the persistent challenge of HPAI H5N1 in Egypt. This study illuminated spatiotemporal outbreak dynamics, with specific attention on Menofia governorate. 

Results: 

Despite the region’s early poultry impacts, initial outbreaks did not originate from Menofia in studied epidemic waves (EWs). Outbreak risk spatial distribution displayed an escalating pattern at the northern border, followed by risk reduction through the sixth EW. The predominant hot spot region was localized within rural districts, particularly villages, while urbanization coincided with lower outbreak density. Observed smoothed densities revealed epidemic propagation within urban centers, preceding its transition to new areas and establishing direct connections with neighboring cities. Primary cluster prognostication was plausible, occurring in regions previously hosting elevated relative risk clusters during preceding EWs. Identification of enduring pinpoint clusters, persistent for extended durations, indicated close contact dynamics and localized viral circulation within populations. 

Conclusion: 

This study highlights the significance of customized regional interventions based on the rigorous epidemiological framework. This approach is pivotal in the profound comprehension of endemicity dynamics, efficiently limits geographical infection spread, and contains outbreaks within delineated areas.

Source: Open Veterinary Journal, https://doi.org/10.5455/OVJ.2024.v14.i11.20

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A Potent #Pandemic Avian #Influenza Virus #Vaccine Based on a 4th Generation Fully Deleted #Adenoviral #Vector

Abstract

The GreVac system was developed as a fast and flexible plug-and-play vaccine platform based on an architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors. The present study established the potency of the GreVac technology. It demonstrated that the GreFluVie5 vaccine fully protected mice against lethal challenges with the A/Vietnam/1203/2004 (H5N1) pandemic avian influenza virus. The GreFluVie5 vector delivered a transgene expression cassette for the H5 hemagglutinin and N1 neuramidase influenza genes. Its fd Ad genome was carried in a capsid of the human serotype 5 (Ad5). The efficacies of three different doses and three different administration routes were compared in the mouse model. The vaccine fully protected animals against viral challenges with the wild-type A/Vietnam/1203/2004 virus, whose replication in the recipients' lungs was terminated. It induced strong immune responses. The present experiments also revealed that the intra muscular (i.m.) delivery route of GreFluVie5 was more efficient than sub cutaneous (s.c.) or intra nasal (i.n.) ones. Based on the results of this trial and GreVac's intrinsic versatility and fast development time, we believe that this platform is ideally suited to swiftly deliver powerful vaccines to infectious diseases with high eruption potentials.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.30.630761v1

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#France - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 Two poultry farms in Normandie Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6127

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#Albania - High pathogenicity avian #influenza #H5N1 viruses (poultry) (Inf. with) - Immediate notification

 Backyard poultry in Tiranë Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6130

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

 A wild bird in Brandenburg Region. 

Source: WOAH, https://wahis.woah.org/#/in-review/6133

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A low pathogenic avian #influenza A/Mallard/South Korea/KNU2019-34/2019 (#H1N1) virus has the potential to increase the #mammalian #pathogenicity

Abstract

Influenza, a highly contagious respiratory infectious disease caused by an influenza virus, is a threat to public health worldwide. Avian influenza viruses (AIVs) have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome. Here, we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models. In addition, we assessed the pathogenicity of AIVs in ferret models. Moreover, we compared the ability of viruses to replicate in mammalian cells, as well as the receptor-binding preferences of AIV isolates. Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation. Of the 24 AIV isolates tested, A/Mallard/South Korea/KNU2019-34/2019 (KNU19-34; H1N1) caused severe bodyweight loss and high mortality in mice. The virus replicated in the lungs, kidneys, and heart. Importantly, KNU19-34-infected ferrets showed high viral loads in both nasal washes and lungs. KNU19-34 replicated rapidly in A549 and bound preferentially to human like α2,6-linked sialic acids rather than to avian-like α2,3-linked sialic acids, similar to the pandemic A/California/04/2009 (H1N1) strain. Gene segments of KNU19-34 were distributed in Egypt and Asia lineages from 2015 to 2018, and the virus had several amino acid substitutions compared to H1N1 AIV isolates that were non-pathogenic in mice. Collectively, the data suggest that KNU19-34 has zoonotic potential and the possibility of new mutations responsible for mammalian adaptation.

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X24002062?via%3Dihub

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LC-MS/MS characterization of #SOBERANA®02, a #RBD - #tetanus toxoid conjugate #vaccine against #SARS-CoV-2

Abstract

SOBERANA-02 is a safe and effective conjugate vaccine against SARS-CoV-2, produced using the maleimide-thiol chemistry. In this vaccine, the Cys538 in the recombinant receptor binding domain (RBD) of SARS-CoV-2 is linked, through a thiosuccinimide linker, to lysine residues of tetanus toxoid (TT) preparation. LC-MS/MS analysis revealed that TT is a complex mixture of proteins, similar to other TTs where the detoxified tetanus neurotoxin (d-TeNT) has been shown to be the most abundant protein (30-56%), regardless the quantification method used. The fifteen most abundant proteins account for approximately 78% of the total proteins. LC-MS/MS analysis of the activation process showed that 102 out of 107 lysine residues in the d-TeNT incorporated a maleimide group. In contrast, when tryptic peptides isolated by Ni2+-NTA affinity chromatography, were analyzed by LC-MS/MS, only 22 Lys residues in the d-TeNT were cross-linked to the RBD C-terminal tryptic peptide (538CVNF541-HHHHHH), probably due to steric hindrance. Twelve and eighteen conjugation sites were assigned based on the identification of linear peptides carrying a conjugated lysine residues (K(+1454.58 Da) or K(+1472.59 Da)) and cross-linked peptides with stabilized linker forms, respectively. Eight conjugation sites were coincidently assigned by both strategies. The assignment of the conjugation sites was manually validated by observed regularities (z equal or higher to 3+, XIC, immonium ions, specific linker fragment ions) not considered by the identification software (PEAKS, Kojak and pLink2). The RBD was also conjugated, but to a lesser extent, to ten other low abundance carrier proteins. To our knowledge, this work is the first report of conjugation site assignment in a TT-based conjugate vaccine.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.27.630511v1?rss=1

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Enhanced #RNA #replication and #pathogenesis in recent #SARS-CoV-2 #variants harboring the L260F mutation in NSP6

Abstract

The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape. Apart from extensive evolution in the Spike protein, non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated, suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replication. NSP6 emerged as a hotspot with a distinct L260F mutation independently arising in the BQ.1.1 and XBB.1.16 variants. Using mutant and revertant NSP6 viral clones, the L260F mutation was validated to enhance viral replication in cells and increase pathogenesis in mice. Notably, this mutation enhanced host lipid droplet consumption by NSP6 without impacting its known ER-zippering function or double-membrane vesicle morphology. Collectively, a systematic analysis of RNA replication of recent Omicron variants defined NSP6 key role in viral RNA replication that provides insight into evolutionary trajectories of recent variants with possible therapeutic implications.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.30.628795v1?rss=1

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#USA, #Oregon: State ends year with highest #pertussis case count since 1950

As Oregon sweeps past the 1,100 cases mark, health officials remind everyone that vaccination against whooping cough is best way to prevent transmission

PORTLAND, Ore.—Oregon swept past the 1,100 mark for the number of pertussis cases it’s seen during 2024, beating its 2012 record of 910 cases in a single year—and making the need for people to stay up to date with their vaccinations all the more urgent.

As of Monday, Dec. 30, Oregon Health Authority registered 1,105 cases of pertussis—also known as whooping cough—during 2024. There were 44 outbreaks, although the majority of cases were sporadic individual or household-related cases and not associated with outbreaks. The 2024 count represents the highest number of pertussis cases reported in Oregon in a single year since 1950, when 1,420 cases were reported.

Since 2003, eight Oregonians with pertussis have died. Five were younger than 4 months old, and there have been three deaths in adults – one in 2023 and two in 2024.

While Oregon didn’t beat its 74-year record for most cases in a year, 1,105 is still an extremely high number for a vaccine-preventable disease, said Paul Cieslak, M.D., medical director for communicable diseases and immunizations at OHA’s Public Health Division. It’s also a stark reminder of how quickly the bacterial infection can spread and cause illness, particularly among people who are under- or unvaccinated.

“The pertussis vaccine is a public health success story in terms of its effectiveness in reducing severe illness and deaths from the disease—particularly among infants,” Cieslak said.

According to data from the epidemiologists in Oregon Public Health Division’s Acute and Communicable Disease Prevention Section, the median age of the 2024 cases is 12; 7.2% of cases are less than a year old, 80% are 18 or younger and 50% are female. About half of the cases are up to date with pertussis vaccines.

Lane County has reported the highest number of pertussis cases this year with 315. Rounding out the top five counties are Multnomah, 235 cases; Clackamas, 135; Washington, 119; and Marion, 75.

Pertussis case counts vary considerably from year to year, routinely reaching triple digits. However, during the COVID-19 pandemic, restrictions such as masking requirements and school closures were in effect, which kept annual case counts low, Cieslak said. Vaccination rates also slipped.

“People were less motivated to get vaccinated against pertussis when there was less concern they would be exposed to the infection in the first place,” he said.

But with pertussis activity so high this year, there are more opportunities for people to be exposed, Cieslak noted. Those who are unvaccinated or too young to be vaccinated, such as infants, are at the highest risk from infection, with babies most likely to be hospitalized with pertussis.

But there are ways to protect vulnerable individuals. Pregnant people can protect their young babies by getting the Tdap vaccine—which protects against tetanus, diphtheria and pertussis—at 27–36 weeks’ gestation. Mothers will make antibodies and pass them to their babies across the placenta, protecting them from the moment of birth. It is recommended during each pregnancy.

“In recent years, about two-thirds of pregnant Oregonians have been getting vaccinated during pregnancy,” Cieslak said. “However, only 11 of the mothers of the 80 infant cases this year had documentation of having gotten the recommended shot.”

Vaccination against pertussis is routinely recommended for infants, children, adolescents and adults. Children should receive the DTaP vaccine against diphtheria, tetanus and pertussis at 2, 4, 6 and 15 to 18 months old, and again at age 4 to kindergarten age. All persons 10 years old and older should receive a single dose of Tdap.

“Additionally, when pertussis strikes a household in which an infant or pregnant person lives, we recommend all members of the household receive a course of antibiotics effective against Bordetella pertussis—typically, a five-day course of azithromycin,” Cieslak said.

Source: Department of Health, https://content.govdelivery.com/accounts/ORHA/bulletins/3c9f333

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#Risk #assessment of 2024 #cattle #H5N1 using age-stratified #serosurveillance data

ABSTRACT

The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024. Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1) to general population. In the initial screening of 180 serum specimens encompassing all age groups, 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old. Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1] vs 27.9 [95% CI 21.0-37.0], P=0.0039), but there was no statistically significant difference between H5N1 and H3N2 nAb titer. There was no difference in demographics, comorbidities and clinical frailty scores between individuals with detectable H5N1 nAb and those without. Our findings suggest that most individuals lack nAb response against 2024 cattle H5N1 and there is an urgency to develop and evaluate H5N1 vaccine or prophylactic monoclonal antibodies. Immune imprinting may be responsible for the cross neutralization between H5N1 and H1N1 among older adults.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.12.23.24319580v1

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#Origin, spread, and interspecies #transmission of a dominant #genotype of BJ/94 #lineage #H9N2 avian #influenza viruses with increased #threat

Abstract

The H9N2 subtype of avian influenza viruses (AIVs) is widely prevalent in poultry and wild birds globally, with occasional transmission to humans. In comparison to other H9N2 lineages, the BJ/94 lineage has raised more public health concerns; however, its evolutionary dynamics and transmission patterns remain poorly understood. In this study, we demonstrate that over three decades (1994–2023), BJ/94 lineage has undergone substantial expansion in its geographical distribution, interspecies transmission, and viral reassortment with other AIV subtypes, increasing associated public health risks. These changes were primarily driven by the emergence of a dominant genotype G57. In the first decade, G57 emerged in East China and rapidly adapted to chickens and spread across China. Since 2013, the G57 genotype has expanded beyond China into eight other countries and reassorted with various AIV subtypes to form new zoonotic reassortants. Chickens have played a key role in the generation and circulation of the G57 viruses, with ducks and other poultry species likely assuming an increasingly importantly role. Over the past decade, G57 has been more frequently detected in wild birds, mammals, and humans. Additionally, Vietnam has emerged as a new hotspot for the international spread of G57. Our results suggest that the BJ/94 lineage H9N2 virus may continue to overcome geographical and species barriers, with potentially more severe consequences.

Source: Virus Evolution, https://academic.oup.com/ve/article/10/1/veae106/7919252

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#Germany - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 A poultry farm in Bayern Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6131

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High Pathogenicity Avian #Influenza Virus (HPAIV) #H5N1 clade 2.3.4.4b recovered from a kelp #gull (Larus dominicanus) in the South Shetland Islands, #Antarctica

Abstract

Whole-genome analysis of the earliest-detected High Pathogenicity Avian Influenza Virus (HPAIV) H5N1 clade 2.3.4.4b detected in Hannah Point, Antarctica (January 2024) reveals close relatedness to strains that circulated in pinnipeds and seabirds along the Atlantic coast of South America during the second half of 2023.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.29.630510v1?rss=1

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Dona Antonia de Ipenarrieta y Galdos and her Son, Diego Velazquez (c.1631)

 

Credits: Public Domain.

Source: WikiArt, https://www.wikiart.org/en/diego-velazquez/dona-antonia-de-ipenarrieta-y-galdos-and-her-son

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The #PA-X #host shutoff site 100 V exerts a contrary effect on viral #fitness of the highly pathogenic #H7N9 #influenza A virus in mice and chickens

ABSTRACT

Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed “host shutoff.” Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery. IAV PA-X is one of these factors that selectively shuts off the global host genes. However, the specific role of PA-X host shutoff activity in viral fitness of IAV remains poorly understood. Herein, we successfully mapped PA-X 100 V as a novel site important for host shutoff of the H7N9 and H5N1 viruses. By analysing the polymorphism of this residue in various subtype viruses, we found that PA-X 100 was highly variable in H7N9 viruses. Structural analysis revealed that 100 V was generally close to the PA-X endonuclease active site, which may account for its host shutoff activity. By generating the corresponding mutant viruses derived from the parental H7N9 virus and the PA-X-deficient H7N9 virus, we determined that PA-X 100 V significantly enhanced viral fitness in mice while diminishing viral virulence in chickens. Mechanistically, PA-X 100 V significantly increased viral polymerase activity and viral replication in mammalian cells. Furthermore, PA-X 100 V highly blunted the global host response in 293T cells, particularly restraining genes involved in energy metabolism and inflammatory response. Collectively, our data provided information about the intricate role of the PA-X host shutoff site in regulating the viral fitness of the H7N9 influenza virus, which furthers our understanding of the complicated pathogenesis of the influenza A virus.

Source: Virulence, https://www.tandfonline.com/doi/full/10.1080/21505594.2024.2445238

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#USA, Snow #Geese Test Presumptive Positive for Avian #H5 #Influenza; #Delaware #poultry producers encouraged to take precautions

 {Excerpt}

DOVER, Del. (Dec. 28, 2024) – The Delaware Department of Natural Resources and Environmental Control (DNREC) and the Delaware Department of Agriculture (DDA) announced today that laboratory testing conducted by the University of Delaware’s Allen Laboratory, part of the National Animal Health Laboratory Network, has returned presumptive positive findings of H5 avian influenza in sick and dead snow geese collected on December 27, 2024, in coastal Sussex County. 

In response to the findings, the state of Delaware has established a Joint Information Center with DNREC, DDA, the Delaware Division of Public Health (DPH) and the Delaware Emergency Management Agency (DEMA).

The detections mark the Delmarva region’s most recent confirmation of H5 avian influenza in wild birds since May 2022, when the virus was found through wildlife surveillance in black vultures in Harford County, Md. Avian influenza is known to be carried by wild birds, especially waterfowl, raptors, and vultures.

Avian influenza is a highly contagious airborne respiratory virus that spreads quickly among birds through nasal and eye secretions and manure. Snow geese, which are waterfowl, are known to migrate from the Arctic and form large flocks in Delaware each winter. Due to close contact with thousands of other snow geese while feeding and roosting, they can get sick and die. It is unknown when or where the snow geese may have acquired the virus given their highly migratory nature and association with other waterfowl and waterbirds throughout the Atlantic Flyway through which they travel into Delaware and more southern states.

People should not touch or handle injured, sick, or dead birds. Special attention should be paid to keep pets and children away from these wild birds and bird droppings.

Even with the ongoing detections of HPAI in wild birds, poultry, and dairy cattle in North America, continuing testing of people who are in close contact with infected animals indicates a low risk to the general public’s health. The H5N1 virus has infected very few people and has not been documented to be transmitted between people. The proper handling and cooking of all poultry and eggs to an internal temperature of 165°F is recommended as a general food safety precaution.

(...)

Source: Department of Health, https://news.delaware.gov/2024/12/28/snow-geese-test-presumptive-positive-for-avian-influenza-delaware-poultry-producers-encouraged-to-take-precautions/

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Molecular #Evolution of the #H5 and #H7 Highly Pathogenic Avian #Influenza Virus #Haemagglutinin Cleavage Site Motif

ABSTRACT

Avian influenza viruses are ubiquitous in the Anatinae subfamily of aquatic birds and occasionally spill over to poultry. Infection with low pathogenicity avian influenza viruses generally leads to subclinical or mild clinical disease. In contrast, highly pathogenic avian influenza viruses emerge from low pathogenic forms and can cause severe disease associated with extraordinarily high mortality rates. Here, we describe the natural history of avian influenza virus, with a focus on H5Nx and H7Nx subtypes, and the emergence of highly pathogenic forms; we review the biology of AIV; we examine cleavage of haemagglutinin by host cell enzymes with a particular emphasis on the biochemical properties of the proprotein convertases, and trypsin and trypsin-like proteases; we describe mechanisms implicated in the functional evolution of the haemagglutinin cleavage site motif that leads to emergence of HPAIVs; and finally, we discuss the diversity of H5 and H7 haemagglutinin cleavage site sequence motifs. It is crucial to understand the molecular attributes that drive the emergence and evolution of HPAIVs with pandemic potential to inform risk assessments and mitigate the threat of HPAIVs to poultry and human populations.

Source: Reviews in Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/rmv.70012

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Virological and #antigenic characteristics of #SARS-CoV-2 #variants #LF721, #NP1, and #LP81

Abstract

XEC and KP.3.1.1 have surpassed KP.3 to become the globally dominant lineages due to their unique NTD mutations. However, several emerging JN.1 sublineages, such as LF.7.2.1, MC.10.1, NP.1, and, especially, LP.8.1, have demonstrated superior growth advantages compared to XEC. It is critical to access the virological and antigenic characteristics of these emerging SARS-CoV-2 variants. Here, we found that LF.7.2.1 is significantly more immune invasive than XEC, primarily due to the A475V mutation, which enabled the evasion of Class 1 neutralizing antibodies. However, LF.7.2.1's weak ACE2 binding affinity substantially impaired its fitness. Likewise, MC.10.1 and NP.1 exhibited strong antibody immune evasion due to the A435S mutation, but their limited ACE2 engagement efficiency restricted their growth advantage, suggesting that A435S may regulate the Spike conformation, similar to the NTD glycosylation mutations found in KP.3.1.1 and XEC. Most importantly, we found that LP.8.1 showed comparable humoral immune evasion to XEC but demonstrated much increased ACE2 engagement efficiency, supporting its rapid growth. These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 These findings highlight the trade-off between immune evasion and ACE2 engagement efficiency in SARS-CoV-2 evolution, and underscore the importance of monitoring LP.8.1 and its descend lineages.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.12.27.630350v1?rss=1

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