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Assessment of cross-reactive neutralizing #antibodies induction against #H5N1 clade 2.3.4.4b by prior seasonal influenza #immunization in retail #workers

Abstract Highly pathogenic avian influenza (HPAI) H5N1 has been a global concern since its emergence in 1997, causing widespread outbreaks in birds and sporadic human infections . The clade 2.3.4.4b H5N1 virus has rapidly expanded across continents, infecting numerous mammalian species . In 2024, it was detected in dairy cattle for the first time in the U.S., along with human cases following exposure . In Canada , the first human case of this avian influenza was reported in a critically ill adolescent in late 2024. No human-to-human transmission has been documented, but concerns persist regarding mutations associated with enhanced virulence and human adaptation . Although seasonal influenza vaccines are not directed against H5N1, studies suggest that pre-existing immunity from prior infections or vaccinations may provide partial protection against severe H5N1 infections through cross-reactive immune response . Given the ongoing circulation of avian influenza and the rise in human infec...

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

  The Official Veterinary Services (OVS) received a notification of acute mortality, neurological and digestive signs in a breeder farm . From the start of the OVS investigation, the premise was quarantined, including suspension of the movement of birds and products. Laboratory analysis identified H5N1 virus clade 2.3.4.4b. OVS is conducting an epidemiological investigation of the event and implementing the restrictions and measures in accordance with the National Contingency Plan for high pathogenicity avian influenza (HPAI). Source: WOAH,  https://wahis.woah.org/#/in-review/6484 ____

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

Sudden death of birds, clinical signs, non-commercial hobby flock of hens, products are used exclusively for own consumption in the same household. Source: WOAH,  https://wahis.woah.org/#/in-review/6471 ____

Novel #Orthohantavirus Associated with #Hantavirus Pulmonary Syndrome in Northern #Argentina

Abstract In this work, we performed the genetic characterization of a new variant of orthohantavirus associated with a fatal case of hantavirus pulmonary syndrome , outside the known endemic region, in northwestern Argentina . We first confirmed an orthohantavirus infection by ELISA , testing for the detection of IgM and IgG antibodies. Then, we extracted RNA from 100 microliters of serum, the only sample available, followed by RT-PCR. The amplicons were sequenced using Sanger and next-generation sequencing technology. We obtained partial sequences of 1253 bp, 799 bp and 1675 bp from the S-, M- and L-segments, respectively, showing low sequence identities with all the previously characterized hantaviruses (10.9%, 13.5% and 15.1% of the divergence, respectively). The phylogenetic analysis showed that this virus belongs to the Orthohantavirus andesense species (ANDV), and among the ANDV-like variants, it is more closely related to the Lechiguanas clade . Similar percentages of divergence...

Yellow fever - Region of the #Americas (#WHO D.O.N., May 16 '25)

{Summary} Situation at a glance From 29 December 2024 and as of 26 April 2025 (with data for Ecuador updated as of 2 May 2025), a total of 212 confirmed human cases of yellow fever , including 85 deaths , have been reported to WHO by five countries in the Region of the Americas ( case fatality rate (CFR) 40% ).  The cases have been reported in the Plurinational State of Bolivia, Brazil, Colombia, Ecuador and Peru .  The 212 confirmed yellow fever cases reported so far in 2025 represent a threefold increase compared to the 61 confirmed cases reported in 2024.  WHO is supporting affected countries in implementing coordinated actions to respond to the yellow fever cases and outbreaks.  This includes:  - enhancing preventive measures,  - strengthening surveillance and case management,  - improving risk communication and community engagement, and  - implementing immunization activities.  The current yellow fever situation in the Americas is driven...

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (CDC, May 16 '25)

  {Excerpt} Time Period: April 27, 2025 - May 03, 2025 -- H5 Detection :  8 sites ( 2.0% ) - No Detection :  402 sites ( 98.0% ) - No samples in last week :  67 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

#Molnupiravir or #nirmatrelvir–ritonavir plus usual care vs usual care alone in patients admitted to #hospital with #COVID19 (RECOVERY)...

Summary Background Molnupiravir and nirmatrelvir–ritonavir are oral antivirals that have shown efficacy in preventing disease progression in outpatients with COVID-19. We aimed to evaluate these treatments for patients hospitalised with COVID-19 pneumonia, for whom data on these antivirals are scarce. Methods The RECOVERY trial is a randomised, controlled, open-label, adaptive platform trial testing treatments for COVID-19 . In this study we report the molnupiravir and nirmatrelvir–ritonavir comparisons from the RECOVERY trial. In each comparison, participants aged 18 years and older were randomly allocated (1:1) to the relevant antiviral (5 days of molnupiravir 800 mg twice daily or 300 mg nirmatrelvir and 100 mg ritonavir twice daily) in addition to usual care, or to usual care alone. The molnupiravir comparison was conducted at 75 hospitals in the UK, two in Nepal, and two in Indonesia ; the nirmatrelvir–ritonavir comparison was conducted at 32 hospitals in the UK. Participants coul...

Identification of naturally occurring #drug-resistant #mutations of #SARS-CoV-2 papain-like #protease

Abstract The SARS-CoV-2 papain-like protease (PLpro) is a cysteine protease that cleaves viral polyproteins and antagonizes the host immune response during viral replication. Jun12682 and PF-07957472 are the first-in-class PLpro inhibitors showing potent in vivo antiviral efficacy in mouse models . In this study, we characterize naturally occurring mutations at residues located at the drug-binding site of Jun12682. The results reveal several PLpro mutants showing significant drug resistance while maintaining comparable enzymatic activity as the wild-type PLpro. The physiological relevance of the identified drug-resistant mutants, including E167G and Q269H, is validated through independent serial viral passage experiments. Molecular dynamics simulations and perturbative free energy calculations show that drug-resistant PLpro mutants weaken hydrogen bonding and π-π stacking interactions. Collectively, this study identifies E167, Y268, and Q269 as drug-resistant hotspots for PLpro inhibit...

Molecular basis of #influenza #ribonucleoprotein complex #assembly and processive #RNA synthesis

Abstract Influenza viruses replicate and transcribe their genome in the context of a conserved ribonucleoprotein (RNP) complex . By integrating cryo–electron microscopy single-particle analysis and cryo–electron tomography , we define the influenza RNP as a right-handed, antiparallel double helix with the viral RNA encapsidated in the minor groove . Individual nucleoprotein subunits are connected by a flexible tail loop that inserts into a conserved pocket in its neighbor. We visualize the viral polymerase in RNP at different functional states , revealing how it accesses the RNA template while maintaining the double-helical architecture of RNP by strand sliding. Targeting the tail loop binding interface, we identify lead compounds as potential anti-influenza inhibitors . These findings elucidate the molecular determinants underpinning influenza virus replication and highlight a promising target for antiviral development. Source: Science,  https://www.science.org/doi/10.1126/science...

#Statement on the #antigen #composition of #COVID19 #vaccines (#WHO, May 15 '25)

  Key points -- Vaccination remains an important public health countermeasure against COVID-19 . As per the WHO Director General’s standing recommendations for COVID-19, Member States are recommended to continue to offer COVID-19 vaccination based on the recommendations of the WHO Strategic Advisory Group of Experts on Immunization (SAGE). -- SARS-CoV-2 continues to undergo sustained evolution since its emergence in humans, with important genetic and antigenic changes in the spike protein. -- The objective of an update to COVID-19 vaccine antigen composition is to enhance vaccine-induced immune responses to circulating SARS-CoV-2 variants. -- The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) advises manufacturers that monovalent JN.1 or KP.2 vaccines remain appropriate vaccine antigens ; monovalent LP.8.1 is a suitable alternative vaccine antigen . -- In accordance with WHO SAGE policy, vaccination should not be delayed in anticipation of access to vacci...

Genetic diversity of #H5N1 avian #influenza viruses isolated from #birds and #seals in #Russia in 2023

Abstract Thousands of outbreaks of the highly pathogenic avian influenza A(H5N1) virus in birds and an increasing number of mammal infections are registered annually. In 2023, multiple avian influenza outbreaks were registered among wild birds, poultry and seals in Russia . The genetic characterization of seventy-seven avian viruses and three viruses from seals showed that they belonged to the 2.3.4.4b clade and represented four distinct reassortant genotypes . The majority of viruses represented genotype BB , which was widespread in Europe in 2023. Viruses from seals and four viruses from birds , isolated from outbreaks in the Far East region , belonged to the G1 (A3) genotype and had the amino acid substitution N319K in the NP protein , previously associated with an increased virulence for mammals . In addition, one virus of the G10 genotype and two viruses, representing a previously undescribed genotype (designated as Ru-23-G4) were identified. The viruses analyzed showed normal inh...

#Investigation of #Influenza #H5N1 Virus #Neutralization by Quadrivalent Seasonal #Vaccines, #UK, 2021–2024

Abstract We tested cross-neutralization against highly pathogenic avian influenza A(H5N1) virus in adults vaccinated with 2021–2023 seasonal quadrivalent influenza vaccine in the United Kingdom. Seasonal quadrivalent influenza vaccines are unlikely to protect vulnerable persons against severe H5N1 disease during widespread transmission. Enhanced measures are needed to protect vulnerable people from H5N1 virus infection. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/6/24-1796_article ____

Emergence of #Antigenic #Variants in #Bovine #H5N1 #Influenza Viruses

ABSTRACT The recent emergence of the H5N1 influenza virus in dairy cattle has raised significant public health concerns . Using a previously established pseudovirus-based neutralization assay , we evaluated the impact of emerging hemagglutinin (HA) mutations on the efficacy of current candidate vaccine viruses (CVVs). Neutralization analysis revealed that the cow-derived H5N1 virus showed up to a 2.2-fold reduction in sensitivity compared to the CVV homologous neutralization titers. Among the 1,453 HA sequences analyzed from cow-derived H5N1 viruses, we identified four major mutations (E2K, D104G, V147M, and S336N) that emerged after the initial isolation, with 134 isolates (9.22%) harboring all four mutations . These multi-mutation variants exhibited up to a 3.3-fold reduction compared with the CVV homologous neutralization titers. Single-mutation analysis demonstrated that the D104G mutation , present in 47.8% of sequences, markedly contributed to antibody escape . Our findings highl...

Effects of #JAK #inhibitors in adults admitted to #hospital due to #COVID19: a systematic review and individual participant data meta-analysis of randomised clinical trials

Summary Background Evidence from randomised clinical trials (RCTs) of Janus kinase (JAK) inhibitors —compared with usual care or placebo—in adults treated in hospital for COVID-19 is conflicting. We aimed to evaluate the benefits and harms of JAK inhibitors compared with placebo or usual care and whether treatment effects differed between prespecified participant subgroups. Methods For this systematic review and individual participant data meta-analysis (IPDMA), we searched Medline via Ovid, Embase via Elsevier, the Cochrane Central Register of Controlled Trials , the Cochrane COVID-19 Study Register, and the COVID-19 L·OVE Platform, including backward and forward citation searching (last search Nov 28, 2024), for RCTs (unpublished or published in any format and any language) that randomly assigned adults (aged ≥16 years) admitted to a hospital due to COVID-19 to receive either a JAK inhibitor (any type) or no JAK inhibitor (ie, received site-specific standard of care with or without p...

#Measles - #Morocco (#WHO D.O.N., May 13 '25)

{Summary} Situation at a glance Since late 2023, Morocco has been experiencing a widespread measles outbreak . Cases have been recorded across all regions of the country, particularly among children and people who are unvaccinated . In response, the Ministry of Health and Social Protection (MOHSP), in collaboration with relevant sectors, activated the National Center for Public Health Emergency Operations , launched urgent catch-up vaccination campaigns , and strengthened surveillance, case management, and risk communication and community engagement efforts. Measles is a highly transmissible viral disease that can lead to severe complications and death. While Morocco has made significant progress toward measles elimination, the disease remains endemic in the country. The overall risk is assessed as moderate at the national level and moderate at the regional level , particularly given the risk of cross-border transmission in areas with low vaccination coverage. (...) Source: World Healt...

#China reported eight new #human cases of #Influenza A #H9N2 and one new case of Influenza A #H10N3 (HK CHP, May 13 '25)

  {Excerpt} Avian influenza A(H9N2) :  -- New Cases (New Deaths): 8 (0)  - Chongqing Municipality :  - 1) A 67-year-old man with onset on April 18, 2025.  - Guizhou Province :  - 2)  A one-year-old girl with onset on April 7, 2025.  - 3) A one-year-old girl with onset on April 15, 2025.  - Hunan Province :  - 4) A five-year-old boy with onset on April 1, 2025. - 5) A seven-year-old girl with onset on April 1, 2025.  - 6) A one-year-old girl with onset on April 3, 2025.  - 7) A five-year-old boy with onset on April 19, 2025 - Yunnan Province : - 8) A one-year-old girl with onset on April 2, 2025 Avian influenza A(H10N3) :  - Guangxi Zhuang Autonomous Region :  - 1) A 68-year-old woman with onset on April 13, 2025.  (...) Source: Centre for Health Protection, Hong Kong PRC SAR,  https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk19.pdf ____

#Philippines - High pathogenicity avian #influenza #H5N9 viruses (#poultry) (Inf. with) - Immediate notification

The affected population are ducks grazing in a rice field situated within Camaligan, Camarines Sur where they may have come into contact with wild birds carrying the virus. Source: WOAH,  https://wahis.woah.org/#/in-review/6473 ____

Effectiveness of integrated #vector #management on the incidence of #dengue in urban #Malaysia: a cluster-randomised controlled trial

Summary Background Malaysia is one of the southeast Asian countries hardest hit by dengue . We implemented a proactive integrated vector management (IVM) approach in a large non-blinded, cluster-randomised controlled trial to quantify its effectiveness on dengue incidence in urban settings. Methods In this cluster-randomised controlled trial we enrolled low-cost and medium-cost residential housing blocks in the Federal Territory of Kuala Lumpur and Putrajaya with recurrent dengue outbreaks. Of the 329 eligible sites, 139 were randomly allocated to receive IVM measures (community engagement, targeted outdoor residual spraying using K-Othrine Polyzone , and deployment of autodissemination devices to target both larval and adult mosquitoes) and 141 received routine vector control activities, stratified by block housing cost. The primary outcome was the comparison of dengue incidence between the two groups using information provided by the national e-Dengue surveillance system. Routine vec...

Dose response comparison of #Nipah virus #strains #Malaysia and #Bangladesh in #hamsters exposed by the intranasal or intraperitoneal route

Abstract Nipah virus, a zoonotic pathogen, can cause debilitating disease and death in humans. Currently, countermeasures are limited , with several in various stages of testing but none yet FDA-approved for human use. Evaluation of countermeasure candidates requires safety testing in humans, as well as efficacy testing against lethal challenge in animal models . Herein, we describe the characterization and comparison of the intraperitoneal and intranasal Syrian golden hamster models for Nipah virus strains Malaysia and Bangladesh . Overall, the intraperitoneal route of exposure resulted in a more consistent lethal outcome, regardless of virus strain. Therefore, the IP model was subsequently used to evaluate the use of Favipiravir as a potential positive control for future studies investigating NiV countermeasures. In contrast to prior reported results regarding Favipiravir in Nipah virus-infected hamsters, Favipiravir was only fifty percent effective at preventing death following leth...

Pregnant Dairy #Heifers Express #Influenza A Virus #Receptors in the Mammary #Gland

Abstract Highly pathogenic avian influenza (HPAI) A(H5N1) virus emerged in lactating dairy cattle in March 2024, causing mastitis-related disease and infections in other farm animals and workers . Recent work identified α2,6 and α2,3-linked sialic acids (SA), which serve as influenza virus receptors, in the lactating bovine mammary gland ; however, their distribution across stages of mammary growth and development remains unknown. We compared the distribution of tissue sialylation in mammary glands of prepubertal dairy calves , pregnant dairy heifers , and lactating cows . Mammary glands at all physiological stages expressed both α2,6 SA, the preferred receptor linkage for human influenza viruses, and α2,3 SA, the preferred receptor linkage for avian influenza viruses. Importantly, mammary glands of pregnant dairy heifers exhibited the highest overall expression of α2,3 SA, observed in both tissue and alveolar lumens. Our results suggest that pregnant dairy heifers, like lactating dair...