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Significance Anti-influenza therapeutics remain essential for the control of influenza infections , which may require hospitalization for the most severe cases. Hemagglutinin (HA) and neuraminidase (NA), the two membrane glycoproteins of the influenza virus, play crucial roles in the viral replication cycle. While many monoclonal antibodies and small-molecule inhibitors target HA or NA, each faces limitations tied to their individual properties. We developed an antibody–drug conjugate (ADC) by covalently linking the NA inhibitor zanamivir to MEDI8852, an HA stem-specific monoclonal antibody . The MEDI8852–zanamivir conjugate targets both HA and NA and offers robust and long-lasting protection in mice against lethal infections with influenza A and B viruses. This approach represents an addition to anti-influenza therapy. Abstract Influenza remains a significant public health threat . Both monoclonal antibodies and small-molecule inhibitors can target the influenza surface glycoproteins ...

ABSTRACT The highly pathogenic avian influenza viruses (HPAIVs) of subtype H5 , particularly those of the currently circulating clades 2.3.2.1 and 2.3.4.4, are largely responsible for the sporadic human infections that frequently present with a high case fatality rate . Consequently, there is an urgent necessity for the development of advanced antiviral therapeutic options against the H5 HPAIVs. Herein, the yeast two-hybrid system was employed for identifying seven nanobodies that bind the HA1 domain of hemagglutinin (HA). Among these nanobodies, Nb10 was found to exhibit high-affinity and broad-spectrum neutralization capacity against viruses of clades 2.3.2.1 and 2.3.4.4 under both in vitro and in vivo conditions. Surprisingly, Nb10 exhibited excellent efficacy against the recombinant viruses Re6/PR8, Re8/PR8, Re10/PR8, Re11/PR8, and Re14/PR8 of the subtype H5, with average half-maximal inhibitory concentrations ranging from 0.01 to 0.42 µg/mL in a microneutralization assay. Furtherm...

 A wild Booted Eagle in HaZafon Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6408 ____

Abstract Background and Objectives :  The Netherlands faces zoonotic disease risks due to its dense human and livestock populations . The 2009 H1N1 outbreak highlighted the pandemic potential of influenza virus reassortment. Effective preparedness requires integrating behavioural and epidemiological models . Human behaviour, shaped by personal, social, and institutional factors , is critical in detecting, intervening, and treating diseases. Using the Theory of Planned Behaviour (TPB), a framework was developed integrating knowledge from the TPB to improve early detection and response, using (zoonotic) swine influenza as a case study.  Material and Methods :  Within the framework we defined the desired outcome : timely detection and notification of symptomatic (and hypothetical zoonotic) swine influenza to prevent its spread. Actions, such as symptom recognition and disease reporting, were linked to key drivers extracted from the TPB and disease transmission modelling. Exp...

Abstract The H5 Avian Influenza A virus infection has emerged as a global concern , particularly in the ASEAN region . This viral infection poses a significant threat to the poultry industry, public health, and regional economies . This region’s reliance on poultry production and the zoonotic potential of H5 subtypes, with documented transmission to various mammalian species and humans , necessitates proactive mitigation strategies. Over the years, comprehensive efforts such as surveillance, vaccination programs, biosecurity measures, and public health education have been implemented to keep outbreaks at bay. In this review, we provide a thorough overview of the H5 infections in the ASEAN region, focusing on the unique challenges and successes in this geographic area. We analyze epidemiological trends , including specific high-risk populations and transmission patterns, and assess the socioeconomic impact of H5 outbreaks on local communities. We also examine regional responses , highli...

Highlights •  Enterovirus D68 (EV-D68) was circulating in Europe in 2023 •  Most EV-D68 cases were captured through clinical EV surveillance •  Phylogenetic analysis of the VP1 region revealed a distinct B3-derived lineage •  The identified B3 lineage presented a previously undescribed residue change, D554E Abstract Background Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges . Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution. Study design Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of...

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/giorgione/judith ____

Abstract The risk of a respiratory viral pandemic is significant , including from the now widespread panzootic H5N1 influenza virus , highlighting the need for effective, stable, and inexpensive vaccine technologies that elicit strongly protective immunity. Intranasal vaccines can stimulate local immune responses at the site of natural respiratory viral infection, a key characteristic that can not only reduce morbidity and mortality caused by respiratory viruses but also potentially reduce viral transmissibility to limit outbreaks. Nucleic acid vaccines are now a valuable tool in pandemic responses, with high potency and rapid adaptability to target circulating or emerging viral strains; however, data are limited on which vaccine attributes are needed for efficient transmucosal delivery and immune stimulation following intranasal delivery. To demonstrate proof of concept , here we have developed a replicon vaccine expressing an H5 influenza antigen that uses a nanostructured lipid carr...

Abstract H9N2 avian influenza virus (AIV) is endemic in poultry worldwide and increasingly zoonotic . Despite the long-term widespread use of inactivated vaccines , H9N2 AIVs remain dominant in chicken flocks. We demonstrated that inactivated vaccines did not prevent the replication of H9N2 AIVs in the upper airway of vaccinated chickens. Viral transmission was enhanced during sequential passage in vaccinated chickens, which was attributed to the restricted production of defective interfering particles and the introduction of stable mutations (NP-N417D, M1-V219I, and NS1-R140W) which enhanced viral replication. Notably, the genetic diversity of H9N2 AIVs was greater and included more potential mammal/human-adapted mutations after passage through vaccinated chickens than through naïve chickens, which might facilitate the emergence of mammal-adapted strains. By contrast, vaccines inducing cellular/mucosal immunity in the upper respiratory tract effectively limit H9N2 AIV. These findings ...

  Ann Intern Med DACSO CC Coadministration of RSV + influenza or COVID-19 vaccines was noninferior to separate administration for immune responses in adults aged >/=50 y. Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00904. PubMed           Abstract available AMAN M, Jeevananthan A, Martinez-Cruz M, Namasingh N, et al Endocrinology: What You May Have Missed in 2024. Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00990. PubMed           Abstract available HAMED HKA, Nachman A, Riopel N, Schuster M, et al Infectious Diseases: What You May Have Missed in 2024. Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00925. PubMed           Abstract available CORONADO GD, Petrik AF, Thompson JH, Leo MC, et al Patient Navigation to Improve Colonoscopy Completion After an Abnormal Stool Test Result : A Randomized Controlled Trial. Ann Intern Med. 2025 Apr 1. doi: ...

  Ann Intern Med DACSO CC Coadministration of RSV + influenza or COVID-19 vaccines was noninferior to separate administration for immune responses in adults aged >/=50 y. Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00904. PubMed           Abstract available Antimicrob Agents Chemother PANG Y, Li H, Chen X, Cao Y, et al A phase I, single-center, randomized, open-label, three-period crossover study to evaluate the drug-drug interaction between ZSP1273 and oseltamivir in healthy Chinese subjects. Antimicrob Agents Chemother. 2025;69:e0172924. PubMed           Abstract available ZHAO L, Li C, Wang M, Zhou M, et al Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier. Antimicrob Agents Chemother. 2025 Mar 10:e0155624. doi: 10.1128/aac.01556. PubMed           Abstract available Biochem Biophys Res Co...

{Auto translated} www.gob.mx/salud The Ministry of Health reports the detection of the first human case of avian influenza A (H5N1) in Mexico .  The case occurred in a three-year-old girl residing in the state of Durango . On April 1 , the Institute of Epidemiological Diagnosis and Reference (InDRE) confirmed the result of influenza A ( H5N1 ). The patient initially received treatment with oseltamivir and is currently hospitalized in a tertiary care unit in the city of Torreón, where her condition is reported to be serious .  Once the case was confirmed , the following actions were immediately implemented:  -- Notification to the World Health Organization, in accordance with the protocol established for this purpose in the International Health Regulations.  Health -- Health personnel from the Durango and Coahuila Health Services were trained in relation to the National Guide for the preparation, prevention and response to a zoonotic influenza outbreak or event at the...

ABSTRACT As companion animals, dogs are susceptible to various subtypes of influenza A virus (IAV), with the H3N2 and H3N8 subtypes of canine influenza virus (CIV) stably circulating among canines . Compared to the H3N8 CIV, the H3N2 CIV is more widely prevalent in canine populations and demonstrates increased adaptability to mammals , potentially facilitating cross-species transmission . Therefore, a comprehensive elucidation of the mechanisms underlying H3N2 CIV adaptation to mammals is imperative. In this study, we serially passaged the GD14-WT strain in murine lungs , successfully establishing a lethal H3N2 CIV infection model . From this model, we isolated the lethal strain GD14-MA and identified the key lethal mutations PA(S184N) and PB2(E627K). Moreover, the GD14-ma[PA(S184N)+PB2(E627K)] strain exhibited markedly enhanced pathogenicity in dogs . Viral titers in lung tissues from infected dogs and mice showed that GD14-ma[PA(S184N)+PB2(E627K)] does not increase its pathogenicity ...

  {Excerpt} Time Period: March 23, 2025 - March 29, 2025 -- H5 Detection :  9 sites ( 2.2% ) -- No Detection :  400 sites ( 97.8% ) -- No samples in last week :  228 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

{England} Backyard flock of 40 chickens. Increased mortality and other clinical signs were reported. Samples tested positive for HPAI H5N1. Source: WOAH,  https://wahis.woah.org/#/in-review/6401 ____

Summary Background The substantial burden of post-COVID-19 condition (also known as long COVID) underscores the need for effective pharmacological interventions. Given that viral persistence has been hypothesised as a potential cause of long COVID, antiviral therapy might offer a promising approach to alleviating long COVID symptoms. We therefore investigated the efficacy, safety, and tolerability of nirmatrelvir–ritonavir for treating long COVID. Methods In this phase 2, decentralised, double-blind, randomised controlled trial , adults (aged ≥18 years) from the 48 states across the contiguous USA, with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks, were eligible for inclusion. Key exclusion criteria were use of nirmatrelvir–ritonavir within the previous 2 months, CYP3A4-dependent medications, or strong CYP3A4 inducers; acute medical illness such as SARS-CoV-2 infection within the past ...

Abstract Influenza A(H1N1)pdm09 virus carrying an I38N substitution was detected in an untreated teenager in Japan . The I38N mutant virus exhibited reduced susceptibility to baloxavir but remained susceptible to neuraminidase inhibitors and showed reduced growth capability . Monitoring antiviral drug susceptibility of influenza viruses is necessary to aid public health planning and clinical recommendations. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/5/24-1123_article ____

Abstract In February 2023, the government of Equatorial Guinea declared an outbreak of Marburg virus disease . We describe the response structure and epidemiologic characteristics , including case-patient demographics, clinical manifestations, risk factors , and the serial interval and timing of symptom onset, treatment seeking, and recovery or death . We identified 16 laboratory-confirmed and 23 probable cases of Marburg virus disease in 5 districts and noted several unlinked chains of transmission and a case-fatality ratio of 90% (35/39 cases). Transmission was concentrated in family clusters and healthcare settings . The median serial interval was 18.5 days ; most transmission occurred during late-stage disease . Rapid isolation of symptomatic case-patients is critical in preventing transmission and improving patient outcomes; community engagement and surveillance strengthening should be prioritized in emerging outbreaks. Further analysis of this outbreak and a One Health surveillan...

Highlights •  Phylogenetic analysis of genotype B3.13 and D1.1 across the species. •  Mutations on the receptor binding sites related to receptor preferring. •  Host adaptability differences between B3.13 and D1.1. •  Antivirals resistance mutations emergence of genotype B3.13 and D1.1. Abstract The recent report of the first fatality associated with infection by influenza virus H5N1 clade 2.3.4.4b, identified as genotype D1.1, which is distinct from the B3.13 genotype, has sparked fears of a potential human pandemic . However, the genetic relationships between B3.13 and D1.1, as well as their origins, host adaptability, and antiviral resistance, remain poorly understood . Here we conducted a comprehensive phylogenetic and comparative analysis of H5N1 clade 2.3.4.4b across multiple species , in order to identify the molecular characteristics and frequency of resistance mutations in these two genotypes, elucidate their evolutionary trajectories , and assess their impl...

Abstract Zoonotic diseases have received significantly more attention over the last few decades , emerging with increasing frequency and causing the majority of notable disease outbreaks in this century, including the COVID-19 pandemic . As human activities and shifting climate patterns induce changes in the environment that alter habitat and range of reservoir species , the potential for human and animal interactions will increase and enhance the opportunity for spillover . Thus, any emergency response preparedness planning must take into account the function and coordination of agencies across the sectors of human, animal and environmental health. Within the Commonwealth of Pennsylvania a table-top exercise was performed to evaluate a multi-agency response during a hypothetical zoonotic disease investigation. The exercise was evaluated by the participants to gain feedback on the overall process and lessons learned. Here, we describe the tabletop exercise scenario and the insights gai...