Role of Nonpharmaceutical #Interventions during 1918–1920 #Influenza #Pandemic, #Alaska, #USA

Abstract

Previous studies investigating the 1918–1920 influenza pandemic have provided a comprehensive overview of the spread of the pandemic and possible explanations for high mortality rates in Alaska, USA. Our understanding of the role of nonpharmaceutical interventions (NPIs) is limited, however. To gain an overview of various agencies’ efforts to protect communities during the pandemic, we conducted a mixed-method assessment of a large pool of digitized historical newspapers and archival materials covering Alaska’s local and territorial responses to the pandemic. The study encompassed 14 local units of Alaska that implemented NPIs during October 1918–January 1919. Analyses indicated that 8 local units avoided the outbreak by implementing NPIs and that the other 6 units controlled the spread of influenza by implementing NPIs after the virus was introduced. In addition, some Indigenous communities escaped the pandemic by implementing mandatory and voluntary restrictions. Information on NPI effects of could guide future influenza pandemic preparedness and response.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/7/24-1048_article

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Host #origin is a determinant of #coevolution between gene segments of avian #H9 #influenza viruses

ABSTRACT

Several emerging influenza viruses, including H7N9 and H5N6 viruses, trace their origins to reassortment with H9N2 viruses that contributed internal gene segments. However, the evolutionary constraints governing the reassortment of H9N2 viruses remain unknown. In seasonal human influenza A viruses, gene segments coevolve at both the nucleotide and amino acid levels. Here, we demonstrate that evolutionary relationships between gene segments, including polymerase subunits in human H3N2 viruses, differ from avian H9 viruses. Avian H9 viruses were characterized by little coevolution between gene segments or between polymerase subunits. Strikingly, protein trees built from avian H9 polymerase subunits diverge despite known functional constraints on polymerase evolution. The evolutionary divergence observed between gene segments of avian H9 viruses was consistent across isolates from different continents, suggesting that coevolution between H9 gene segments is not dependent on regionally defined avian lineages. Instead, coevolution between gene segments was only found in H9 viruses that crossed the species barrier into humans. Our study reveals the role of the host in the coevolution of influenza gene segments and suggests that high reassortment potential in avian species may be a consequence of evolutionary flexibility between gene segments.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01518-24?af=R

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater (#CDC, June 13 '25)

 

{Excerpt}

Time Period: June 01, 2025 - June 07, 2025

- H5 Detection: 4 sites (1.1%)

- No Detection: 370 sites (98.9%)

- No samples in last week: 73 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

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

 Sea Otters in Hokkaido Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6551

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Re-Emergence of #Usutu Virus and Spreading of #WestNile Virus #Neuroinvasive Infections During the 2024 Transmission Season in #Croatia

Abstract

Neuroinvasive arboviruses such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV), Usutu virus (USUV), and Toscana virus (TOSV) have (re-)emerged with increasing incidence and geographic range. We analyzed the epidemiology of arboviral infections in Croatia during the 2024 transmission season. A total of 154 patients with neuroinvasive diseases (NID), 1596 horses, 69 dead birds, and 7726 mosquitoes were tested. Viral RNA was detected using RT-qPCR. IgM/IgG-specific antibodies were detected using commercial ELISA or IFA, with confirmation of cross-reactive samples by virus neutralization test. RT-qPCR-positive samples were Sanger sequenced. Arboviral etiology was confirmed in 33/21.42% of patients with NID. WNV was most frequently detected (17/11.03%), followed by TBEV (10/6.49%), USUV (5/3.24%), and TOSV (1/0.64%). WNV infections were reported in regions previously known as endemic, while in one continental county, WNV was recorded for the first time. USUV infections re-emerged after a six-year absence. In addition to human cases, acute WNV infections were recorded in 11/395 (2.78%) of horses and two dead crows. WNV IgG seropositivity was detected in 276/1168 (23.63%) and TBEV IgG seropositivity in 68/428 (15.88%) horses. None of the tested mosquito pools were positive for WNV and USUV RNA. Phylogenetic analysis showed the circulation of WNV lineage 2 and Usutu Europe 2 lineage. Climate conditions in 2024 in Croatia were classified as extremely warm, which could, at least in part, impact the quite intense arboviral season. The spreading of flaviviruses in Croatia highlights the need for continuous surveillance in humans, animals, and vectors (“One Health”).

Source: Viruses, https://www.mdpi.com/1999-4915/17/6/846

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Broad geographical #circulation of a novel #vesiculovirus in #bats in the #Mediterranean region

Abstract

Bats are the natural reservoirs for a variety of emerging and re-emerging viruses. Among them, rabies virus (genus Lyssavirus, family Rhabdoviridae) is one of the first and most emblematic described in these animals. Since its first description, several new bat lyssaviruses have been regularly identified. In addition to lyssaviruses, other bat rhabdoviruses have also been discovered, including members of the genera Vesiculovirus, Ledantevirus and, more recently, Alphanemrhavirus and Tupavirus. However, the family Rhabdoviridae is one of the most abundant and diverse viral families, with 434 officially recognized species, divided into 5 subfamilies and 56 different genera. The number of rhabdoviruses associated with bats is therefore probably higher than that currently available. In this study, we first developed and validated a combined nested RT-qPCR technique (pan-rhabdo RT-nqPCR) dedicated to the broad detection of animal rhabdoviruses. After validation, this technique was used for a large retrospective screening of archival bat samples (n = 1962), including blood (n = 816), brain (n = 723) and oral swab (n = 423). These samples were collected from various bat species over a 12-year period (2007–2019) in 9 different countries in Europe and Africa. A total of 23 samples (1.2%) from bat species Miniopterus schreibersii, Rhinolophus euryale and Rhinolophus ferrumequinum tested positive for rhabdovirus infection, including 17 (2.1%) blood and 6 (1.4%) oral swab samples, all collected from bats originating from the Mediterranean region. Complete virus genome sequences were obtained by next-generation sequencing for most of the positive samples. Molecular and phylogenetic analysis of these sequences demonstrated that these virus isolates, named Mediterranean bat virus (MBV), were closely related and represented a new species, Mediterranean vesiculovirus, within the Vesiculovirus genus. MBV was more specifically related to other bat vesiculoviruses previously described from China and North America, together clustering into a distinct group of bat viruses within this genus. Interestingly, our results suggest that MBV is widespread, at least in the western part of the Mediterranean region, where it circulates in the blood of several bat species. These results expand the host range and viral diversity of bat vesiculoviruses, and pave the way for further studies to determine the transmission route and dissemination dynamics of these viruses in bat colonies, as well as to assess their potential threat to public health.

Author summary

Bats are the natural hosts for a wide variety of viruses, particularly those belonging to the family Rhabdoviridae, which include the lyssaviruses, the etiological agents of rabies. This viral family is one of the most abundant and diverse, with 434 officially recognized species. However, the current diversity of these viruses in bats remains poorly understood. To address this, we developed a new method for detecting rhabdoviruses in bat samples collected over a period of 12 years in several European and African countries. From nearly 2,000 samples, we discovered a new rhabdovirus, which was named Mediterranean bat virus (MBV). MBV has been detected in the blood and oral swabs of specific bat species (Rhinolophus sp. and Miniopterus schreibersii) living on both sides of the Mediterranean region. Based on phylogenetic analysis, we determined that MBV represented a unique group within the genus Vesiculovirus, but still related to other bat vesiculoviruses discovered in China and North America. These results expand the host range and viral diversity of bat rhabdoviruses, and pave the way for further studies to determine the transmission route and dissemination dynamics of these viruses in bat colonies, as well as to assess their potential threat to public health.

Source: PLoS Neglected Tropical Diseases, https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013172

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#Management and #outcomes of #children hospitalised with #COVID19 including Incidental and Nosocomial infections in #Australia 2020-2023: a national surveillance study

Highlights

• Acute COVID-19 usually causes mild illness even in young and immunosuppressed children

• Nosocomial SARS-CoV-2 infection is associated with more severe disease

• Concurrent serious bacterial infection is rare in children admitted with acute COVID-19.

ABSTRACT

Background

Management and outcomes of children hospitalised with acute SARS-CoV-2 infection may differ throughout the pandemic or with admission type (clinical COVID-19, incidental COVID-19 or nosocomial infection).

Objectives

Describe the severity, management and outcomes of hospitalised children with acute SARS-CoV-2 infection in Australia across the first 4 years of the pandemic and compare between admission types, SARS-CoV-2 variants, age groups and immune status.

Study design

A multi-centre prospective cohort study of 6,009 children aged 0-16 years between January 2020 to June 2023.

Results

Most children (84.3%) did not receive respiratory support, 33.4% received antibiotics and 8% were admitted to intensive care unit (ICU). Infants <6 months old were more likely to be admitted with clinical COVID than older children (12-16 years). Older children were more likely to receive antibiotics (27.8% vs 43.9%), corticosteroids (11.3% vs 34.1) or ICU admission (5.2% vs 13.5%). Compared to immunocompetent children, the immunosuppressed (7.7%) were more likely to have nosocomial infection (9.5% v 3.9%), receive antibiotics (57% vs 25%) or antivirals (18% vs 4.4%), but less likely to require respiratory support (93.4% vs 83.8%) or ICU admission (3.5% vs 8%). Children with nosocomial SARS-CoV-2 infection had higher rates of invasive ventilation (8%) and ICU admission (21%) compared to those with clinical (2.1% and 7.1% respectively) or incidental COVID-19 (4.8% and 9.1% respectively).

Conclusions

Acute COVID-19 generally caused mild disease in hospitalised children, with management and outcomes differing by age and admission type. Similar outcomes were observed across the pandemic. Nosocomial SARS-CoV-2 infection was associated with more severe disease.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000666?dgcid=rss_sd_all

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#Mpox in #Africa: What we know and what is still lacking

Abstract

Emerging as a major global health threat, Mpox previously known as Monkeypox has drawn attention due to a worrying surge in cases. This zoonotic disease, native to Central and West Africa, is marked by fever, rash, and lymphadenopathy and is primarily spread through direct contact with infected animals or people and indirectly through contaminated objects. Recent studies have indicated possible sexual transmission, underscoring how human behavior and environmental changes are increasing its prevalence, even though human-to-human transmission is less efficient than that of smallpox. Mpox is endemic in several African countries, and currently, the infection has spread in non-endemic countries, including Rwanda, Uganda, and Kenya. Democratic Republic of Congo is the epicenter of the current Mpox outbreak. From January 1, 2022, to August 6, 2024, sixteen African countries reported Mpox outbreak. Several factors, including population immunity deficiencies and changes to the environment and ecology, have led to the widespread of Mpox in Africa. Challenges such as the fragile healthcare system, limited vaccine availability and access, weak surveillance, and low public awareness poses difficulty in containing the infection in affected countries. Given the potential of Mpox to disrupt several sectors including health systems, which may ultimately reverse progress in achieving the sustainable development goals by 2030. It is imperative for countries, both within and outside Africa, to extend financial aid and human resources to combat the infection effectively.

Source: PLoS Neglected Tropical Diseases, https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013148

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

A small commercial flock of 69 chickens, 23 ducks and 5 geese. Increased mortality reported in chickens as well as a drop in egg production in the ducks. Samples were taken and tested positive for HPAI H5N1. Location: Kirklees, West Yorkshire, England.

Source: WOAH, https://wahis.woah.org/#/in-review/6552

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Ten Previously Unassigned #Human #Cosavirus #Genotypes Detected in Feces of #Children with Non-Polio #AFP in #Nigeria in 2020

Abstract

Since its discovery via metagenomics in 2008, human cosavirus (HCoSV) has been detected in the cerebrospinal fluid (CSF) and feces of humans with meningitis, acute flaccid paralysis (AFP), and acute gastroenteritis. To date, 34 HCoSV genotypes have been documented by the Picornaviridae study group. However, the documented genetic diversity of HCoSV in Nigeria is limited. Here we describe the genetic diversity of HCoSV in Nigeria using a metagenomics approach. Archived and anonymized fecal specimens from children (under 15 years old) diagnosed with non-polio AFP from five states in Nigeria were analyzed. Virus-like particles were purified from 55 pools (made from 254 samples) using the NetoVIR protocol. Pools were subjected to nucleic acid extraction and metagenomic sequencing. Reads were trimmed and assembled, and contigs classified as HCoSV were subjected to phylogenetic, pairwise identity, recombination analysis, and, when necessary, immuno-informatics and capsid structure prediction. Fifteen pools yielded 23 genomes of HCoSV. Phylogenetic and pairwise identity analysis showed that all belonged to four species (eleven, three, three, and six members of Cosavirus asiani, Cosavirus bepakis, Cosavirus depakis, and Cosavirus eaustrali, respectively) and seventeen genotypes. Ten genomes belong to seven (HCoSV-A3/A10, A15, A17, A19, A24, D3, and E1) previously assigned genotypes, while the remaining thirteen genomes belonged to ten newly proposed genotypes across the four HCoSV species, based on the near-complete VP1 region (VP1*) of the cosavirus genome. Our analysis suggests the existence of at least seven and eight Cosavirus bepakis and Cosavirus eaustrali genotypes, respectively (including those described here). We report the first near-complete genomes of Cosavirus bepakis and Cosavirus depakis from Nigeria, which contributes to the increasing knowledge of the diversity of HCoSV, raising the number of tentative genotypes from 34 to over 40. Our findings suggest that the genetic diversity of HCoSV might be broader than is currently documented, highlighting the need for enhanced surveillance.

Source: Viruses, https://www.mdpi.com/1999-4915/17/6/844

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Impact of #serum versus #anticoagulant-containing #plasma on #influenza virus #neuraminidase-based serological assays

Abstract

The influenza virus neuraminidase (NA) is a promising target for next-generation influenza vaccines but standardized protocols for NA-based serological assays are lacking. Previous studies have demonstrated discordant results from haemagglutination inhibition and live virus microneutralization assays when comparing matched serum and plasma samples. It is therefore important to consider is the choice of serum or plasma samples in assays measuring influenza virus NA-specific antibodies. Here, we compared antibody titres against influenza A and B virus NAs in matched serum and different types of plasma using an enzyme-linked lectin assay (ELLA) and an enzyme-linked immunosorbent assay (ELISA). We observed good correlations between titres determined in serum and different types of plasma. However, there was variable and often poor agreement in the nominal titre values obtained from serum and different kinds of plasma in both ELLA and ELISA, with plasma samples often resulting in lower titres compared to serum samples. We also found differences in NA-specific responses to seasonal influenza vaccination assessed in serum versus plasma. Overall, our data demonstrate discrepancies between NA-specific antibody measurements in serum and plasma. We recommend the consistent use of serum as an important part of standardising NA-based serological assays.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.07.658460v1

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#Lanka virus, a #Mus booduga-borne #orthohantavirus #infection-associated febrile illness in #SriLanka

Abstract

Background

In Sri Lanka, a high seroprevalence of antibodies against hantaviruses was reported in communities affected by chronic kidney disease of unknown etiology (CKDu). Recently, two rodent-borne hantaviruses, Lanka virus and Anjozorobe virus, were identified in these areas. However, it is unclear which virus is the source of infection in humans, and its pathogenicity is unknown.

Methodology/principal findings

A total of 181 sera from febrile patients from two CKDu-endemic regions, Girandurukotte and Polonnaruwa, were examined and Lanka virus genome was detected in two IgM-positive febrile patients. Of 76 serum samples from patients with fever of unknown etiology collected during 2016 examined to identify hantavirus genomes, antibodies, and serotypes, 10 were IgG-positive with five of them having IgM also. They were all without clinical features of hemorrhagic fever with renal syndrome, but three patients required treatment in the intensive care unit. A serotyping strategy was established based on the antigenic difference of the glycoprotein Gn of Lanka and Anjozorobe viruses. Using this method, febrile patients were found to be infected with the Lanka virus and none of the patient sera showed Anjozorobe virus infection pattern. Additionally, a total of 373 previously diagnosed seropositive serum samples from CKDu patients and healthy residents were serotyped to categorize 87% of seropositives as Lanka virus infection.

Conclusions/significance

Lanka virus carried by little Indian field mouse (Mus booduga) is transmitted to humans, likely causing febrile illness occasionally while leading to severe disease in some of the febrile patients.

Author summary

Hantaviruses are known to be transmitted by rodents and cause severe diseases such as hemorrhagic fever with renal syndrome (HFRS) in humans. Although there have been few reports of typical HFRS in Sri Lanka, there are many antibody-positive individuals. The antibody positivity rate is particularly high in patients with chronic kidney disease by unknown etiology (CKDu), and the relationship between hantavirus infection and CKDu is being discussed. Meanwhile, rodent surveys have identified Lanka virus in little Indian field mouse (Mus booduga) and Anjozorobe virus in black rat (Rattus rattus) in Sri Lanka. However, it was unclear which virus was infecting the humans and its pathogenicity. This study showed that hantavirus infections in Sri Lanka could be asymptomatic or cause common fever-like symptoms and rarely require treatment in an ICU. It was also shown that the main source of infection is Lanka virus. This study leads us to the starting line of clarifying the Lanka virus-related health risks, such as its association with CKDu.

Source: PLoS Neglected Tropical Diseases, https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013169

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Evaluation of #country #preparedness for #Nipah and avian #influenza #zoonotic viral #threats in #Bangladesh

Highlights

• Systematic and routine monitoring antigenic drift and shift of AIV in wild birds and poultry is needed.

• Community-based surveillance is key for improving NiV case detection.

• Integrated surveillance across One Health sectors is required.

• Lab upgrades to BSL-3 are needed for enhanced biosafety and diagnostics.

Abstract

Nipah and avian influenza viruses (NiV and AIV) are priority zoonotic pathogens in Bangladesh and are also important globally because of their pandemic potential. To understand current strengths, areas for improvement, and opportunities to enhance preparedness for NiV and AIV in Bangladesh, as part of the USAID STOP Spillover program, 47 relevant stakeholders were surveyed, and two country leads of the primary surveillance systems were interviewed. Data was collected focusing on four different areas: research projects, surveillance systems, laboratories, and outbreak risk management systems. Despite progress in recent years, our study reveals significant gaps in preparedness, detection, and response capacities across sectors and highlights the importance of prioritizing extended and targeted surveillance, biosafety solutions for laboratories, and early event detection for resilient defenses against these viruses using a One Health framework.

Source: One Health, https://www.sciencedirect.com/science/article/pii/S2352771425001119?via%3Dihub

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Promising Effects of #Duck #Vaccination against Highly Pathogenic Avian #Influenza, #France 2023–2024

Abstract

Highly pathogenic avian influenza causes substantial poultry losses and zoonotic concerns globally. Duck vaccination against highly pathogenic avian influenza began in France in October 2023. Our assessment predicted that 314–756 outbreaks were averted in 2023–2024, representing a 96%–99% reduction in epizootic size, likely attributable to vaccination.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/7/24-1445_article

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Anti #Matrix Protein 1 Monoclonal #Antibody Neutralizes #Influenza A Virus Subtypes

Abstract

Background: 

Research on monoclonal antibodies (mAb) targeting conserved internal proteins of influenza is limited.The matrix protein 1 (M1), the most abundant and conserved internal protein, serves as an endoskeleton bridging cytoplasmic tails of envelope glycoproteins haemagglutinin (HA), neuraminidase (NA) and matrix protein 2 (M2) with viral ribonucleoprotein particles (vRNPs). Clinical studies reveal significant M1 antibody responses post-infection and vaccination, with demonstrated B and T cell recognition. Our study examines 2B-B10-G9, our lab-synthesized mAb targeting conserved linear epitope of M1 at the C-terminal domain (CTD). 

Methods: 

Binding of 2B-B10-G9 to the purified influenza A viruses (IAV) and influenza B viruses (IBV) were assessed using SDS-PAGE and Western blotting with Image J analysis. Purified viruses included IAV (H1N1, Pandemic (H1N1) 2009 (H1N1pdm09), and H3N2 subtypes) and IBV which was first isolated in 1940 (B/Lee/40), and B/Victoria lineage. Cytotoxicity of 2B-B10-G9 on the Madin-Darby canine kidney (MDCK) cells was studied by MTT (3-(4, 5-dimethylthiazol-2)-2, 5-diphenyltetrazolium bromide) cell proliferation assay to establish in vitro and in ovo treatment doses. In ovo studies involved injecting 2B-B10-G9 into the allantoic cavity of specific pathogen free (SPF) 10-day-old embryonated chicken eggs (ECE) immediately post-infection with influenza A/Puerto Rico/8/1934 (H1N1) followed by RT-qPCR analysis of the virulence genes HA, NA, and PB1 expressions in the allantoic fluid (AF) 48 hours post-infection. 

Results: 

mAb 2B-B10-G9 shows significantly stronger binding to the M1 protein of H1N1 subtype of IAV with respect to H3N2 subtype of IAV (p < 0.001), and it has significantly stronger binding to the M1 protein of H1N1 subtype of IAV with respect to H1N1pdm09 subtype, IBV including B/Lee/40, B/Victoria lineage. (p< 0.0001) mAb 2B-B10-G9 at dose of 40 ug/ml which was determined as an optimal dose according to the MTT assay, significantly reduced plaque-forming units (PFU)/ml of IAV H1N1 and H3N2 subtypes in vitro (p< 0.0001). In ovo treatment of IAV H1N1 subtype at the same dose 40 ug/ml, significantly suppressed the virulence genes HA, NA, and PB1 expressions compared to the untreated group (p< 0.0001, p< 0.001, p< 0.0001, respectively) and mouse isotype IgG1 mAb treated groups (p< 0.01). 

Conclusions: 

These findings highlight that anti-M1 mAb 2B-B10-G9, targeting conserved linear epitope at the CTD of M1 protein, might be considered as a possible therapeutic option for IAV H1N1 and H3N2 subtypes related to its significant recognition and binding, viral neutralization and suppression of expression of virulence genes including HA, NA and PB1.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.09.658662v1

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#Oseltamivir #Treatment vs Supportive Care for Seasonal #Influenza Requiring #Hospitalization

Key Points

-- Question:  In adults with influenza requiring admission to hospital, is oseltamivir treatment within the first 2 days of admission, when compared with supportive care without oseltamivir, associated with a decreased risk of death in hospital?

-- Findings: In this cohort study of 11 073 patients hospitalized with influenza, oseltamivir treatment was associated with an adjusted risk reduction of 1.8% for in-hospital mortality when compared with supportive care.

-- Meaning: The findings of this study support current guidelines that recommend oseltamivir treatment for patients admitted to hospital with influenza; clinical trials should be conducted to generate better quality evidence.

Abstract

Importance  

Current guidelines recommend oseltamivir treatment for all patients hospitalized with influenza, but this guidance is based on suboptimal evidence.

Objective  

To evaluate outcomes associated with oseltamivir treatment when compared with supportive care for severe seasonal influenza requiring hospitalization.

Design, Setting, and Participants  

This retrospective cohort study using target trial emulation included adult patients admitted to hospital with influenza from 30 hospitals in Ontario, Canada, from January 2015 to June 2023. Data were analyzed from November 2024 to March 2025.

Exposure  

Oseltamivir treatment on hospital day 0 or 1 vs supportive care without oseltamivir.

Main Outcome and Measures  

The primary outcome was in-hospital mortality. Secondary outcomes included time to being discharged alive and readmission within 30 days. Overlap weighting of propensity scores was used to balance covariates, and a competing risk model was used to compare time to being discharged alive.

Results  

Of 11 073 patients (mean [SD] age, 72.6 [16.8] years; 5793 female [52.3%]), there were 7632 patients (68.9%) and 3441 patients (31.1%) in the oseltamivir and supportive care groups, respectively. In hospital, 268 patients (3.5%) and 168 patients (4.9%) in the oseltamivir and supportive care groups died, respectively, with an adjusted risk difference of −1.8% (95% CI, −2.8% to −0.9%; P < .001). The oseltamivir treatment group was more likely to be discharged alive (adjusted subdistribution hazard ratio, 1.20; 95% CI, 1.15 to 1.25; P < .001). After discharge, 645 patients (8.5%) and 336 patients (9.8%) were readmitted in the oseltamivir and supportive care groups, respectively, with an adjusted risk difference of −1.5% (95% CI, −2.8% to −0.2%; P = .02).

Conclusions and Relevance  

In this cohort study of patients hospitalized with influenza, oseltamivir treatment was associated with a lower in-hospital mortality risk, earlier discharge, and lower readmission rate, supporting evidence for the current guideline recommendation of oseltamivir treatment for severe influenza. Clinical trials are needed to definitively answer this question.

Source: JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2835158

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Monotherapy with #antibody 1C3 partially protects #Ebola virus-exposed #macaques

ABSTRACT

A cocktail of human monoclonal antibodies 1C3 and 1C11 previously protected macaques from a lethal exposure to either Ebola virus (EBOV) or Sudan virus (SUDV). 1C3 is of particular interest because its paratope strongly binds with unique stoichiometry to the glycoprotein head of several orthoebolaviruses, resulting in neutralization of EBOV and SUDV. Therefore, we evaluated the protective activity of 1C3 as a standalone therapeutic in macaques exposed to either EBOV or SUDV. Two doses of 1C3 monotherapy, administered 4 and 7 days post-exposure, did not protect SUDV-exposed macaques and partially protected EBOV-exposed macaques. Notably, in a macaque that succumbed to EBOV infection, we identified two mutually exclusive escape mutations that emerged immediately after the first dose and resulted in two amino acid changes at the 1C3 binding site. We also detected a subconsensus treatment-emergent mutation likely affecting the 1C3 binding site in all three deceased SUDV-exposed macaques. Our findings highlight combination treatment with 1C11 as critical for protection, particularly against SUDV, and in vivo activity of unpartnered 1C3 as susceptible to rapid EBOV and SUDV escape under therapeutic pressure.

IMPORTANCE

A cocktail of human monoclonal antibodies 1C3 and 1C11 previously protected macaques exposed to a lethal dose of either Ebola virus (EBOV) or Sudan virus (SUDV). Since the unique binding characteristics of 1C3 are of particular interest, we evaluated its protective activity as monotherapy in macaques exposed to either EBOV or SUDV. Two doses of 1C3 alone did not protect SUDV-exposed macaques and only partially protected EBOV-exposed macaques. Importantly, failure to protect was associated with the rapid emergence of previously in vitro-identified escape mutations at the 1C3 binding site, highlighting the importance of its use in combination with 1C11 for protection against fatal disease outcome and avoiding rapid EBOV and SUDV escape. Findings have broader implications for the wise use of combination-based monoclonal antibody therapeutics to improve outcomes and prevent resistance in filovirid diseases.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00296-25?af=R

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Long-term serial passaging of #SARS-CoV-2 reveals #signatures of convergent #evolution

ABSTRACT

Understanding viral evolutionary dynamics is crucial to pandemic responses, prediction of virus adaptation over time, and virus surveillance for public health strategies. Whole-genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has enabled fine-grained studies of virus evolution in the human population. Serial passaging in vitro offers a complementary controlled environment to investigate the emergence and persistence of genetic variants that may confer selective advantage. In this study, nine virus lineages, including four “variants of concern” and three former “variants under investigation,” were sampled over ≥33 serial passages (range 33–100) in Vero E6 cells. WGS was used to examine virus evolutionary dynamics and identify key mutations with implications for fitness and/or transmissibility. Viruses accumulated mutations regularly during serial passaging. Many low-frequency variants were lost, but others became fixed, suggesting either in vitro benefits or at least a lack of deleterious effect. Mutations arose convergently both across passage lines and when compared with contemporaneous SARS-CoV-2 clinical sequences. These mutations included some that are hypothesized to drive lineage success through host immune evasion (e.g., S:A67V, S:H655Y). The appearance of these mutations in vitro suggested key mutations can arise convergently even in the absence of a multicellular host immune response through mechanisms other than immune-driven mutation. Such mutations may provide other benefits to the viruses in vitro, or arise stochastically. Our quantitative investigation into SARS-CoV-2 evolutionary dynamics spans the greatest number of serial passages to date and will inform measures to reduce the effects of SARS-CoV-2 infection on the human population.

IMPORTANCE

The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a challenge for long-term public health efforts to minimize the effects of coronavirus disease 2019. Whole-genome sequencing of outbreak cases has enabled global contact tracing efforts and the identification of mutations of concern within the virus’ genome. However, complementary approaches are necessary to inform our understanding of virus evolution and clinical outcomes. Here, we charted the evolution of the virus within a controlled cell culture environment, focusing on nine different virus lineages. Our approach demonstrates how SARS-CoV-2 continues to evolve readily in vitro, with changes mirroring those seen in outbreak cases globally. Findings of the study are important for (i) investigating the mechanisms of how mutations arise, (ii) predicting the future evolutionary trajectory of SARS-CoV-2, and (iii) informing treatment and prevention design.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00363-25?af=R

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#Japan - #Influenza A #H5N2 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 A wild Peregrine falcon in Kagoshima Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6545

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Multiple introductions of #equine #influenza virus into the #UK resulted in widespread #outbreaks and #lineage #replacement

Abstract

Influenza A viruses (IAVs) are prime examples of emerging viruses in humans and animals. IAV circulation in domestic animals poses a pandemic risk as it provides new opportunities for zoonotic infections. The recent emergence of H5N1 IAV in cows and subsequent spread over multiple states within the USA, together with reports of spillover infections in humans, cats and mice highlight this issue. The horse is a domestic animal in which an avian-origin IAV lineage has been circulating for >60 years. In 2018/19, a Florida Clade 1 (FC1) virus triggered one of the largest epizootics recorded in the UK, which led to the replacement of the Equine Influenza Virus (EIV) Florida Clade 2 (FC2) lineage that had been circulating in the country since 2003. We integrated geographical, epidemiological, and virus genetic data to determine the virological and ecological factors leading to this epizootic. By combining newly-sequenced EIV complete genomes derived from UK outbreaks with existing genomic and epidemiological information, we reconstructed the nationwide viral spread and analysed the global evolution of EIV. We show that there was a single EIV FC1 introduction from the USA into Europe, and multiple independent virus introductions from Europe to the UK. At the UK level, three English regions (East, West Midlands, and North-West) were the main sources of virus during the epizootic, and the number of affected premises together with the number of horses in the local area were found as key predictors of viral spread within the country. At the global level, phylogeographic analysis evidenced a source-sink model for intercontinental EIV migration, with a source population evolving in the USA and directly or indirectly seeding viral lineages into sink populations in other continents. Our results provide insight on the underlying factors that influence IAV spread in domestic animals.

Author summary

Influenza causes significant disease burden in animals, including wild birds, sea lions, pigs, horses, dogs, and more recently, cows. Outbreaks and epizootics of influenza in agricultural species are a threat to food security and the economy whereas in wild animals they could affect biodiversity and conservation efforts. Given the zoonotic nature of influenza viruses and the high levels of contact between domestic animals and humans, animal influenza is also a public health concern. Here, we combined geographical, epidemiological, and virus sequence data to determine key factors that led to one of the largest epizootics of equine influenza in the United Kingdom in decades. We show that an American equine influenza virus lineage was introduced into Europe and replaced the virus lineage that had been circulating in the United Kingdom for nearly 20 years. We also analysed a global dataset of virus genomes and propose a model of equine influenza virus intercontinental migration, in which USA is the main source of viruses to other countries. Our results provide important information concerning the basic principles of influenza virus circulation in animal populations. This is central to devise effective measures of disease control that would increase animal health while reducing zoonotic risk.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013227

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