ETIDIOH - NEW

  {Excerpt} On Sept 4, 2025, the DR Congo Government and Ministry of Health announced a new Ebola virus disease outbreak in the Bulape health zone (Kasai province), marking the end of over 15 years without any reported cases of Ebola virus disease in this region . As of Sept 14, 2025, there were 35 confirmed Ebola virus disease cases and 16 deaths , representing a case fatality rate of 45·7%.1,2 This unexpected resurgence in a region with insufficient preparedness capacity raises serious concerns about potential regional spread, including towards neighbouring Angola. At the same time, DR Congo is experiencing one of the most severe cholera outbreaks of the past decade , with a total of 48 139 cases and 1443 deaths reported between Jan 1 and Aug 24, 2025, resulting in a case fatality rate of 3%.3 By epidemiological week 33, high case fatality rates were reported in the provinces of Kwilu (76 cases, 26 deaths; 44%), Sankuru (42 cases, 6 deaths; 14%), and Equateur (224 cases, 19 death...

  Abstract The current panzootic of high pathogenicity avian influenza (HPAI) H5N1 has been catastrophic for wildlife , and following a significant sweep, clade 2.3.4.4b is found in every region aside from Oceania . Herein, we report the results of our third year of targeted surveillance of incoming migratory seabirds and shorebirds into Australia . We did not find evidence of HPAI H5N1 in any of the birds tested , and there were no reports of HPAI H5N1 in wildlife tested through other surveillance schemes in 2024. Unlike previous years, we detected a diversity of low pathogenicity avian influenza (LPAI) viruses in shorebirds. Through phylogenetic analysis we revealed that the H3N7 and H4N7 viruses recovered from Red-necked Stints were complex mosaic viruses, comprising segments of Eurasian, Australian shorebird, and Australian waterfowl segments . A H1N7 virus detected comprised a wholly Eurasian introduction , confirming this route for avian influenza viruses into Australian ecos...

  Significance The high-resolution cryo-EM structure indicates that the human antibody 6Y13 binds strongly to a conserved pan-H7 epitope on the hemagglutinin head , distinct from the receptor-binding site and lateral patch. However, 6Y13 can broadly neutralize H7 viruses , fully protect H7N9 -infected mice, and potently block receptor binding through mechanisms, independent of Fc-mediated steric hindrance. Abstract Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential . Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks . Here, we isolated a human VH3-30 gene-encoded antibody , designated 6Y13 , from a survivor of H7N9 infection . This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred comple...

  Abstract Samples collected from two avian influenza outbreaks in Bagmati Province in central Nepal between January and March 2023 were positive for H5N1 . Full genomes were generated for both viruses, which revealed that one of the viruses was very similar to clade 2.3.4.4b H5N1 identified in Bangladesh in 2021/2022. The second virus was a reassortant H5N1 virus consisting of four genes (HA, NA, NP, and M) originating from a clade 2.3.2.1a H5N1 and the remaining four genes (NS, PB1, PB2, and PA) originating from a 2.3.4.4b H5N1 . Notably, this second virus had a high identity with 2.3.2.1a clade viruses identified in humans and cats in India in 2024–2025. These are the first full genome sequences of H5N1 avian influenza viruses from Nepal and given the recent human infections by 2.3.2.1a H5N1 viruses in the region, these data will be of interest to both public health and veterinary authorities. Source: Viruses,  https://www.mdpi.com/1999-4915/17/11/1481 ____

  Abstract Mucosal influenza vaccines may provide improved protection against infection and transmission , but their development is hindered by absence of immune correlates of protection . Here, we report a randomized, controlled phase I trial of a recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine formulated with a nanoemulsion adjuvant (W805EC). The vaccine is administered intranasally in two doses 28 days apart at three antigen levels. Controls receive unadjuvanted H5 or placebo. Six months later, participants receive an intramuscular boost with unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine. Primary outcomes are solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, potential immune-mediated conditions, new-onset chronic conditions, and serious AEs. All vaccines are well tolerated. After the intranasal series, hemagglutination inhibition and microneutralization responses are...

  Abstract Background No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa . A replication-competent recombinant vesicular stomatitis virus–vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited. Methods In this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly . Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural h...

  Abstract Influenza virus is transmitted via respiratory expulsions, but detection of infectious virus in such expulsions has been challenging . Here, we describe quantification and genotyping of infectious virus in respiratory particles using a Modular Influenza Sampling Tunnel (MIST). The particles deposit on cell monolayers , enabling culture, quantification, and sequencing of viruses. Concomitantly, water-sensitive paper and fine particle samplers yield respiratory particle counts over a broad size range. Using the MIST, we captured infectious virus from humans experimentally infected with influenza virus on multiple days post-inoculation . The recovered respiratory particles varied in quantity over three orders of magnitude and contained viral genetic variation that was also detected in samples from infected individuals. Expulsion of infectious virus was associated with infectious viral load in saliva and nasopharyngeal swabs and with clinical symptoms . These data reveal the...

  Summary Kyasanur Forest disease is a neglected tick-borne viral haemorrhagic fever endemic to India's Western Ghats , caused by the Kyasanur Forest disease virus , a flavivirus transmitted by Haemaphysalis spinigera ticks . The virus circulates in a sylvatic cycle among monkeys, rodents, shrews, birds, and ixodid ticks , and is transmitted to humans incidentally via tick bites . Since its discovery in 1957 in Karnataka , Kyasanur Forest disease has spread to other Indian states, driven by deforestation , forest fragmentation , and increased human incursion into wildlife habitats . Clinically, the disease manifests in a biphasic pattern , with haemorrhagic and neurotropic presentations . Although a formalin-inactivated vaccine is available , its efficacy is not promising, and no antivirals have been approved to date. Field reports indicate that mortality in monkeys might serve as an early indicator of forthcoming human outbreaks. The transmission dynamics of Kyasanur Forest diseas...

  ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), is characterized by its high contagiousness. The COVID-19 pandemic has exerted profound impacts on human society . The persistent circulation of SARS-CoV-2 in human populations continues to pose re-exposure risks for both vaccinated individuals and those with prior natural infection. Against this epidemiological background, there is an urgent need to characterize the transmission dynamics of SARS-CoV-2 in the context of pre-existing immunity . Using a ferret infection model , this study systematically addresses critical scientific questions , including viral transmission efficiency , temporal patterns of transmissibility , and the ability of pre-existing immunity to mitigate reinfection and viral shedding. The findings provide robust experimental evidence for elucidating the transmission mechanisms of SARS-CoV-2 and offer scientific insights to info...

  Abstract Influenza is a global health concern, causing over 300,000 deaths worldwide annually . Current vaccines and natural infection mainly elicit antibodies against the variable head domain of the hemagglutinin (HA) glycoprotein. While these antibodies are highly neutralizing, the head domain constantly mutates due to selective pressure , causing the immune response to be strain-specific. Targeting the conserved HA stalk domain , however, has been shown to be a promising approach for a broadly protective vaccine . We previously demonstrated that presenting HA in an inverted orientation on virus-like particles (VLPs) significantly enhanced the induction of stalk-directed, cross-reactive antibodies compared to HA presented in a regular orientation. Here, we evaluated the protective efficacy of the inverted HA vaccine (VLP-HAinv) in mice against homologous, heterologous, and heterosubtypic influenza A virus challenges . VLP-HAinv vaccination in mice provided complete protection a...

  Abstract Emerging infectious diseases can have catastrophic impacts on wildlife populations , yet identifying individuals that survived exposure, especially when external symptoms are absent, remains challenging. Since 2021, a virulent strain of highly pathogenic avian influenza virus (HPAIV H5N1 clade 2.3.4.4b) has caused unprecedented mortality in wild birds across continents . Northern Gannets (Morus bassanus) are among the species that suffered significant population declines in Europe and North America . At North America's largest gannet colony ( Bonaventure Island ) dramatic mortality and reproductive failure occurred in 2022. Following this event, researchers noted a subset of gannets displaying irregular iris pigmentation , raising the possibility that this visible change may indicate a lasting effect of infection. Here, we build on earlier observations linking irregular iris pigmentation to HPAIV exposure in gannets using anti-nucleoprotein (NP) and anti-hemagglutinin (H...

  Abstract Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication . Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes . Model simulations suggested lower antiviral potency against pre-Omicron SARS-CoV-2 variants than against Omicron . We estimated that in vitro assays underestimated in vivo potency by 6- to 7-fold against Omicron variants. Our model suggested that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA was underestimated by approximately 0.4 log10 in the two trials conducted while Omicron variants dominated. Viral area under the curve estimates differed significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in...

  Abstract The H5N1 high pathogenicity avian influenza virus (HPAIV) of clade 2.3.4.4b, which spreads globally via wild birds , has become a major public health concern because it can infect a variety of mammals , including humans . In 2024, infection of dairy cattle with H5N1 HPAIV clade 2.3.4.4b was confirmed in the United States , and subsequent human cases were reported. Although these viruses are highly pathogenic in animal models , human infections have generally been mild , revealing a striking discrepancy . Here, we characterized the cattle-derived human H5N1 isolate A/Texas/37/2024 (TX37-H5N1) using three-dimensional human respiratory organoids derived from induced pluripotent stem (iPS) cells. Despite efficient replication , TX37-H5N1 induced minimal interferon and inflammatory cytokine responses . Bulk and single-cell RNA sequencing revealed reduced STAT1-mediated transcriptional activity in TX37-H5N1-infected organoids compared to the historic H5N1 human isolate A/Vietn...

  Abstract Dipeptidyl peptidase-4 (DPP4) is an established receptor for Middle East respiratory syndrome-related coronaviruses (MERSr-CoVs), while recent studies have identified angiotensin-converting enzyme 2 (ACE2) usage in multiple merbecovirus clades . Yet, receptor usage of many genetically diverse bat MERSr-CoVs remains unclear . Here we show that broadly distributed HKU25 clade merbecoviruses use ACE2 , rather than DPP4, as their receptor. Cryo-electron microscopy revealed that HsItaly2011 and VsCoV-a7 strains engage ACE2 similarly to HKU5 but with remodelled interfaces and distinct orthologue selectivity, suggesting a shared evolutionary origin of ACE2 recognition . EjCoV-3, a close relative of the DPP4-using BtCoV422, showed broad multi-species ACE2 tropism and preadaptation to human ACE2 . Several ACE2 glycans and residues within or near the binding interface were identified as determinants of orthologue selectivity. These viruses remain sensitive to several broadly neutr...

  Clin Infect Dis CALABRESE C, Wang Y, Duggal A, Huang S, et al Effectiveness of Nirmatrelvir/Ritonavir or Molnupiravir Use in Immunocompromised Patients on B-Cell-Depleting Therapy With COVID-19: A Target Trial Emulation Study. Clin Infect Dis. 2025 Oct 24:ciaf521. doi: 10.1093. PubMed           Abstract available FONG Y, Huang Y, Huang Y, Woo W, et al Analysis of antibody markers as immune correlates of risk of severe COVID-19 in the PREVENT-19 efficacy trial of the NVX-CoV2373 recombinant protein vaccine. Clin Infect Dis. 2025 Oct 25:ciaf558. doi: 10.1093. PubMed           Abstract available KABORE JL, Laffont B, Diop M, Tardif MR, et al Real-World Effectiveness of Nirmatrelvir-Ritonavir in Preventing Coronavirus Disease 2019-Associated Hospitalization: A Population-Based Cohort Study in the Province of Quebec, Canada. Clin Infect Dis. 2025 Oct 29:ciaf145. doi: 10.1093. PubMed    ...

  Arch Virol YIN Y, Chen J, Chen S, Huang J, et al The SARS-CoV-2 N protein disrupts G3BP1 function and alters lipid metabolism in COVID-19 pathogenesis. Arch Virol. 2025;170:237. PubMed           Abstract available Biochem Soc Trans CALL MJ, Call ME, Wu X Insights from deep mutational scanning in the context of an emerging pathogen. Biochem Soc Trans. 2025;53:1169-1179. PubMed           Abstract available BMC Pediatr VASQUEZ-LOARTE T, Guerra GA, Saldarriaga EM, Torres-Gomez L, et al Healthcare access satisfaction before and during the COVID-19 pandemic among Peruvian children with down syndrome. BMC Pediatr. 2025;25:874. PubMed           Abstract available Drugs SYED YY Clesrovimab: First Approval. Drugs. 2025;85:1487-1492. PubMed           Abstract available J Exp Med BISSETT C, Yong L, Spencer AJ, Ma FNL, et al Heterologo...

  ABSTRACT Subtype H3N2 influenza A viruses (IAVs), which emerged in 1968 to cause a pandemic, have shown continual circulation and adaptation that has necessitated frequent updates of candidate vaccine viruses . Here, we sought to determine how genetic changes in the hemagglutinin (HA) and neuraminidase of 21 antigenically distinct H3N2 IAVs isolated from 1968 to 2019 correlate with mammalian fitness and adaptation. We found a surge of adaptation between 1997 and 2002 , resulting in the emergence of A/Fujian/411/2002 (H3N2) and poor vaccine efficacy , leading to an epidemic during the 2003–2004 season. This surge was characterized by a large reduction in binding to mammalian-type α2,6-linked sialic acids and increased infectivity and replication kinetics in humanized Madin-Darby canine kidney cells. HA glycosylation also increased most rapidly from 1968 to 2004 and then plateaued. Symptomatic infections were only evident in mice following inoculation with viruses isolated in the 1...

  ABSTRACT Systemic spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to extrapulmonary tissues has been observed following acute infections. Autopsy studies further indicate tissue-specific virus diversity, including in immune-privileged sites . Questions remain on the viral dynamics leading to the tissue tropism of SARS-CoV-2, including evolutionary trajectories and functional adaptations that could impact persistence and transmission . In this study, we characterized SARS-CoV-2 genomes from 27 distinct tissues collected from an autopsy case where the patient had a primary immune deficiency . We identified tissue-specific virus genotypes , in some instances coexisting within the same sites, with mutations primarily in the receptor-binding domain of the spike protein. Protein simulations and isolation of infectious virus indicate combinations of spike substitutions that would lead to increased protein stability and stronger binding of the virus to host cells. ...

  ABSTRACT An increase in the number of human cases of influenza A/H5N1 infection in the USA has raised concerns about the pandemic potential of the virus. Pre-existing population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals. Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody titers were detected in a cohort of 73 individuals . Conversely, bovine A/H5N1 NA-binding and neuraminidase-inhibiting antibody titers were comparable to those against a human A/H1N1 NA at baseline . Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1-n...

  Abstract Recently, highly pathogenic avian influenza (HPAI) A (H5N1) clade 2.3.4.4b viruses have caused mass mortality events in seabirds worldwide, raising concern for long-lived species with low reproductive rates. Using individual-level data from the 2022 mass mortality event in northwestern European Sandwich terns (Thalasseus sandvicensis), we show that older individuals were disproportionately more affected , while no sex bias was observed. This age-specific mortality likely removed the most experienced individuals from the population. Our findings highlight a previously underappreciated mechanism through which HPAI outbreaks may impair the resilience of long-lived avian populations . Competing Interest Statement The authors have declared no competing interest. Funder Information Declared German Federal Agency for Nature Conservation (BfN) Federal Ministry for the Environment, Climate Action, Nature Conservation and Nuclear Safety (BMUKN) Source: BioRxIV,  https://www.b...