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#Detection of #Hemagglutinin #H5 #influenza A virus #RNA and model of potential inputs in an #urban #California #sewershed

Abstract In 2024, the highly pathogenic avian influenza A H5N1 caused outbreaks in wild birds, poultry, cows, and other mammals in the United States with 61 human cases also reported by the CDC. Detection of influenza A H5 RNA in wastewater has been previously reported in sewersheds in Texas and North Carolina with nearby impacted dairy herds following the emergence of H5N1 in dairy cows. Here, we conduct retrospective testing of total influenza A and H5 hemagglutinin genes in wastewater as well presenting and applying new assays for detection of H1 and H3 genes across a respiratory virus season in an urban California sewershed from September 2023-May 2024. Total influenza A, H1, and H3 were regularly detected, while H5 was first detected in March . We developed a model that uses Monte Carlo simulations and previously published parameters to estimate numbers of infected people, poultry, wild birds, or liters of H5-contaminated milk required to result in measured H5 concentrations in wa...

Acute #Encephalopathy Associated with #Human #Adenovirus Type 14 Infection in 7-Year-Old Girl, #Japan

Abstract Only 2 cases of human adenovirus type 14 (HAdV-14) have been reported in Japan since 1980. We report a 7-year-old girl with acute encephalopathy associated with HAdV-14 infection genetically similar to strains from the United States . The patient had not had contact with international travelers. HAdV-14 surveillance should be strengthened in Japan. Source: Emerging Infectious Diseases Journal,  https://wwwnc.cdc.gov/eid/article/31/2/24-1168_article _____

Two #genotypes of #H3N2 #swine #influenza viruses identified in #pigs from #Shandong Province, #China

 {Summary} Swine influenza virus (SIV) is a highly contagious pathogen that poses significant economic challenges to the swine industry and carries zoonotic potential , underscoring the need for vigilant surveillance. In this study, we performed a comprehensive genetic and molecular analysis of H3N2 SIV isolates obtained from 372 swine samples collected in Shandong Province, China . Phylogenetic analysis revealed two distinct genotypes . The surface genes of both genotypes clustered with the human-like H3N2 lineage , while the internal genes of one genotype clustered with the 2009 pandemic H1N1 (pdm/09) lineage . In the second genotype, the NS gene clustered with the classical swine (CS) H1N1 lineage , while the remaining internal genes clustered with pdm/09, suggesting stable integration of pdm/09 gene segments into H3N2 SIV. Homology analysis showed over 96% genetic similarity between the isolates and reference strains from China and Brazil , suggesting potential transmission thr...

#USA, #Wastewater #Data for Avian #Influenza A(#H5) (As of Dec. 28 '24)

 {Excerpt} Time Period: December 22 - December 28, 2024 -- H5 Detection : 44 sites ( 18.6% ) -- No Detection : 192 sites ( 81.4% ) -- No samples in last week : 150 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html _____

#USA, #Delaware Announces First Presumptive Positive #H5 Avian #Influenza Case Detected on Kent County {#Poultry} #Farm in 2025

{Excerpt} DOVER, Del. (January 3, 2025) – The Delaware Department of Agriculture announced this morning that preliminary testing of a commercial broiler flock in Kent County , Del., has returned presumptive positive H5 from the University of Delaware’s Lasher Laboratory in Georgetown, part of the National Animal Health Laboratory Network. Additional samples have been sent to the U.S. Department of Agriculture’s National Veterinary Services Laboratory (NVSL) for further confirmation. State officials have quarantined the affected premises , and the birds on the property are being depopulated to prevent the spread of the disease. Birds from the affected flock will not enter the food system. Avian influenza is a highly contagious airborne respiratory virus that spreads quickly among birds through nasal and eye secretions and manure. The virus can be spread from flock to flock, including flocks of wild birds, through contact with infected poultry, equipment, and the clothing and shoes of ca...

Random forest #algorithm reveals novel sites in #HA #protein that shift #receptor binding preference of the #H9N2 avian #influenza virus

Abstract A switch from avian-type α-2,3 to human-type α-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus . Some H9N2 viruses exhibit a preference for binding to human-type α-2,6 receptors . This identifies their potential threat to public health . However, our understanding of the molecular basis for the switch of receptor preference is still limited. In this study, we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin (HA), which are associated with the receptor binding ability of H9N2 avian influenza virus (AIV). Subsequently, these sites were further verified by receptor binding assays. A total of 12 substitutions in the HA protein (N158D, N158S, A160N, A160D, A160T, T163I, T163V, V190T, V190A, D193N, D193G, and N231D) were predicted to prefer binding to α-2,6 receptors . Except for the V190T substitution, the other substitutions were demonstrated to display an affinity for pr...

Highly Pathogenic Avian #Influenza (HPAI) #H5N1 virus in #Finland in 2021-2023 – Genetic diversity of the viruses and infection kinetics in #human dendritic cells

Abstract Highly pathogenic avian influenza (HPAI) H5N1 is known for its virulence and zoonotic potential, infecting birds and mammals , thus raising public health concerns. Since 2021 its spread among birds has led to cross-species transmission causing epizootics among mammals, eventually impacting fur animal farms in Finland in 2023. To analyze the infectivity of the Finnish H5N1 isolates in human cells , representatives of diverse H5N1 isolates were selected based on the genetic differences, host animal species, and the year of occurrence. The infection kinetics of the selected H5N1 isolates from wild pheasant and fox , and fur animals blue fox and white mink were examined in human monocyte-derived dendritic cells (moDCs) with H5N1 human isolate as a control. Although the isolate from pheasant (a wild bird) showed weakly reduced replication and viral protein expression in human cells compared to mammalian isolates, no discernible differences in virus replication in moDCs was observed...

Are we serologically prepared against an avian #influenza #pandemic and could seasonal flu #vaccines help us?

ABSTRACT The current situation with H5N1 highly pathogenic avian influenza virus (HPAI) is causing a worldwide concern due to multiple outbreaks in wild birds, poultry, and mammals. Moreover, multiple zoonotic infections in humans have been reported. Importantly, HPAI H5N1 viruses with genetic markers of adaptation to mammals have been detected. Together with HPAI H5N1, avian influenza viruses H7N9 (high and low pathogenic) stand out due to their high mortality rates in humans . This raises the question of how prepared we are serologically and whether seasonal vaccines are capable of inducing protective immunity against these influenza subtypes. An observational study was conducted in which sera from people born between years 1925–1967, 1968–1977, and 1978–1997 were collected before or after 28 days or 6 months post-vaccination with an inactivated seasonal influenza vaccine. Then, hemagglutination inhibition, viral neutralization, and immunoassays were performed to assess the basal pro...

#Vaccination with different group 2 #influenza #subtypes alters epitope targeting and breadth of #hemagglutinin stem–specific human B cells

Abstract The conserved influenza hemagglutinin stem , which is a target of cross-neutralizing antibodies , is now used in vaccine strategies focused on protecting against influenza pandemics . Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2 . Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes ( H3, H7, or H10 ). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive , whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes . The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protectio...

Prior #infection with IBDV prolonged the shedding of a #mallard #H3N8 #influenza A virus (IAV) challenge from oropharyngeal cavity of some #chickens {...}

Abstract Infectious bursal disease virus (IBDV) is endemic worldwide and causes immunosuppression in chickens . We hypothesized that a previous history of IBDV in chickens would render them more susceptible to infection by influenza A viruses (IAVs) from aquatic waterfowl reservoirs . To model this, we inoculated 14 day old specific pathogen free (SPF) chickens with a low pathogenicity avian influenza (LPAI) virus strain from a mallard ( A/Mallard/Alberta/156/01 (H3N8) ) and compared replication and shedding between immunocompetent chickens and chickens that had immune dysregulation due to a prior IBDV infection with strain F52/70 (genogroup A1B1) at 2 days of age. The mallard IAV strain replicated in the upper respiratory tract of the chickens , and virus was shed from the oropharyngeal cavity , but there was no shedding from the cloaca , and no transmission to sentinel chickens . Replication of the mallard IAV in the chicken host was associated with amino acid substitutions in the po...

Identification of a broad-inhibition #influenza #neuraminidase #antibody from pre-existing memory B cells

Highlights -- Both NA-specific antibodies and memory B cells are detected in healthy adults -- NA broad-inhibition monoclonal antibodies are derived from classical memory B cells -- Broad inhibition monoclonal antibodies target the NA conserved enzymatic epitopes -- NA broad-inhibition antibodies protect mice against H1N1 and H5N1- clade 2.3.4.4b Summary Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine . In this study, using influenza neuraminidase (NA) mutant probes , we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzym...

#Combination #chemotherapy, a potential #strategy for reducing the emergence of #drug-resistant #influenza A variants

Natalia A. Ilyushina {a b}, Nicolai V. Bovin {c}, Robert G. Webster {a d}, Elena A. Govorkova  {a b} a} Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA; b} The D.I. Ivanovsky Institute of Virology, Gamaleya 16, Moscow 123098, Russia; c} Shemyakin Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia; d} Department of Pathology, University of Tennessee, Memphis, TN 38105, USA Received 21 November 2005, Accepted 26 January 2006, Available online 21 February 2006. Abstract Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers . On the other hand, the emergence of variants with low susceptibility to the neuraminidase (NA) inhibitors is limited. In the present study we examined whether combination therapy with two classes of anti-influenza drugs can affect the emergence of resistant variants in vitro. We observed that viru...

#USA, #NIH officials assess #threat of #H5N1

 {Excerpt, edited} What Highly pathogenic H5N1 avian influenza A virus (HPAI H5N1) remains a low risk to the general public , and public health experts in the United States believe that available treatments and vaccines , as well as those in development, are sufficient to prevent severe disease . However, the National Institutes of Health (NIH) and its federal partners remain focused on monitoring the virus and evaluating changes , according to leading officials at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. In a commentary published in the New England Journal of Medicine , NIAID Director Jeanne M. Marrazzo, M.D., M.P.H., and Michael G. Ison, M.D., M.S ., chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases, say people should find a balance between enhanced vigilance and “business as usual” with respect to HPAI H5N1 . Since 1996, HPAI H5N1 influenza viruses have circulated in at least 23 countri...

Highly Pathogenic Avian #Influenza A(#H5N1) Virus #Infections in #Humans

Abstract Background Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States , with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. Methods We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. Results Of 46 case patients, 20 were exposed to infected poultry , 25 were exposed to infected or presumably infected dairy cows , and 1 had no identified exposure ; that patient was hospitalized with nonrespiratory symptoms , and A( H5N1 ) virus infection was detected through routine surveillance . Among the 45 case patients with animal exposures , the median age was 34 years , and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 4...

#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 Child...

Immunogenicity of inactivated #H5 avian #influenza #vaccine used in commercial laying #pullet in #Tehran province

Abstract Highly pathogenic avian influenza (HPAI) is a viral disease caused by some H5 and H7 subtypes of influenza virus type A in most species of birds, especially poultry. HPAI viruses are amongst the most challenging viruses that threaten both human and animal health . Consequently, various strategies such as the use of vaccines have been proposed to control the disease. After a catastrophic pandemic and the failure of conventional methods (elimination and extermination) in Iran , multiple vaccines has been used to control the disease. This study investigates the immunogenicity of two recombinant inactivated commercial vaccines of H5N1 and H5N3 subtypes in laying pullet flocks in Tehran Province, Iran . From 32 halls in 6 breeding units of laying pullets, 3200 sera and 800 tracheal and cloacal swabs were collected. After collecting the samples, Serum neutralisation (SN) and hemagglutination inhibition (HI) tests were conducted on sera to determine the serum titers of H5 specific an...

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 pou...

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 mu...