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Crucial role for #iron #metabolism in mediating #influenza A virus #infection and associated disease

Abstract Rationale and Objectives :  Iron availability and metabolism are important in the pathogenesis of bacterial infections . More recently, links have been reported between iron and the severity of viral infections . In this study, we characterize a crucial relationship between iron metabolism and IAV infection and disease.  Methods :  Iron-related gene expression was assessed in human airway epithelial cells (AEC) infected with IAV. AECs were cultured with ferric iron, iron-loaded transferrin, or iron chelator, deferoxamine (DFO), prior to infection with IAV. Mice were placed on a high iron diet for 8 weeks prior to infection with IAV or treated with anti-transferrin receptor-1 (TFR1) antibody during IAV infection. The effects of iron modulation and depletion of TFR1-mediated responses on IAV infection were assessed.  Measurements and main results :  Iron-related gene expression and metabolism are altered systemically and in lung tissues and AECs during IA...

#USA, Monitoring for Avian #Influenza #H5 Virus In #Wastewater {week 11-25}

{Excerpt} Time Period: March 09 - March 15, 2025 -- H5 Detection :  12 sites ( 2.7% ) -- No Detection :  431 sites ( 97.3% ) -- No samples in last week :  177 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/bird-flu/h5-monitoring/index.html ____

Analysis on #epidemiological characteristics of #influenza and #genetic characteristics of influenza virus in 2023-2024 surveillance year in #Shandong Province

Abstract Objective :  To analyze the epidemiological, etiological and genetic characteristics of influenza virus in Shandong Province during 2023-2024.  Methods :  The surveillance data of influenza-like illness (ILI) in sentinel hospitals in Shandong from 2023 to 2024 were collected and analyzed. The isolated influenza strains with hemagglutination titers ≥8 were selected for antigenicity analysis , drug susceptibility test, gene sequencing and evolutionary analysis .  Results :  From 2023 to 2024, the positive rate of influenza virus in Shandong was 8.51% (23 663/277 995), the highest positive rate was in the age group of 5-14 years (15.78%, 6 073/38 478), and the highest positive rate was in the 49th week (35.86%, 2 264/6 313). Both antigenicity analysis and evolutionary analysis showed that the A(H1N1)pdm09 subtype and B(Victoria) strain had good matching effect and close evolutionary distance with the 2023-2024 surveillance year vaccine strain. The A(H3N2) ...

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

On 12th September 2024, a dead Tristan (Brown) Skua (Stercorarius antarcticus hamiltoni) was found at the Gough Island helipad. The following day, a live skua was observed showing suspicious signs of HPAI , including head drooping, lethargy and weakness , and was later reported dead. Between the 12th and 15th September, a total of four skuas were found dead from suspicious causes. Three carcasses were swabbed on the 20th of September and all were confirmed POSITIVE for H5N1 HPAIV by the Animal and Plant Health Agency (Weybridge laboratory) in the UK on the 24th of October 2024. On the day of sampling, the fourth carcass could not be found and was probably taken away by a scavenging skua. Since then, no further signs of HPAI among skuas or in other seabirds breeding on Gough Island, have been observed. Source: WOAH,  https://wahis.woah.org/#/in-review/6354 ____

Post-pandemic #changes in #population #immunity have reduced the likelihood of emergence of #zoonotic #coronaviruses

Abstract Infections caused by endemic viruses , and the vaccines used to control them, often provide cross-protection against related viruses. This cross-protection has the potential to alter the transmission dynamics and likelihood of emergence of novel zoonotic viruses with pandemic potential. Here, we investigate how changes in population immunity after the COVID-19 pandemic have impacted the likelihood of emergence of a novel sarbecovirus , termed SARS-CoV-X. We show that sera from patients with different COVID-19 immunological histories possess cross-neutralising antibodies against the spike (S) protein of multiple zoonotic sarbecoviruses . Mathematical simulations using these viruses show a significant reduction in their likelihood of emergence in populations with current levels of SARS-CoV-2 natural and vaccine-derived immunity, with the outcome determined by the extent of cross-protection and the R_0 of the novel virus. We also show that preventative vaccination programs agains...

#Validation of #H5 #influenza virus subtyping #RTqPCR #assay and low prevalence of H5 #detection in 2024-2025 influenza virus season

Abstract A sustained outbreak of H5N1 influenza virus among wild fowl and domestic livestock has caused more than 70 zoonotic infections in humans in the United States , including one death. The Centers for Disease Control and Prevention has recommended rapid H5 subtyping for all hospitalized cases with influenza A virus infection to enable prompt initiation of antiviral treatment , as well as infection prevention and implementation of public health measures to control spread. To address these needs, we developed a multiplex RT-qPCR assay to subtype H5 influenza virus in nasal, nasopharyngeal, and conjunctival specimens with a limit of detection of 230 copies/mL. No cross-reactivity was observed with other common respiratory viruses, including seasonal H3N2 and H1N1 influenza A viruses. We retrospectively subtyped 590 influenza A-positive clinical specimens processed by University of Washington labs between March 2024 and February 2025, including 512 specimens collected during the 2024...

The #epidemiology of #pathogens with #pandemic potential: A review of key parameters and clustering analysis

Abstract Introduction   In the light of the COVID-19 pandemic many countries are trying to widen their pandemic planning from its traditional focus on influenza. However, it is impossible to draw up detailed plans for every pathogen with epidemic potential. We set out to try to simplify this process by reviewing the epidemiology of a range of pathogens with pandemic potential and seeing whether they fall into groups with shared epidemiological traits.  Methods   We reviewed the epidemiological characteristics of 19 different pathogens with pandemic potential (those on the WHO priority list of pathogens, different strains of influenza and Mpox). We extracted data on the proportion of presymptomatic transmission , incubation period , serial interval and basic reproduction number (R0) for the targeted pathogens. We applied unsupervised machine learning (specifically K-means and hierarchical clustering) to categorise these pathogens based on these characteristics.  Resul...

Modelling #practices, #data #provisioning, #sharing and dissemination needs for #pandemic decision-making: a European survey-based modellers’ perspective

Abstract Introduction :  Advanced outbreak analytics played a key role in governmental decision-making as the COVID-19 pandemic challenged health systems globally. This study assessed the evolution of European modelling practices , data usage, gaps, and interactions between modellers and decision-makers to inform future investments in epidemic-intelligence globally.  Methods :  We conducted a two-stage semi-quantitative survey among modellers in a large European epidemic-intelligence consortium. Responses were analysed descriptively across early, mid-, and late-pandemic phases. Policy citations in Overton were used to assess the policy impact of modelling.  Findings :  Our sample included 66 modelling contributions from 11 institutions in four European countries. COVID-19 modeling initially prioritised understanding epidemic dynamics. Evaluating non-pharmaceutical interventions and vaccination impacts became equally important in later phases. 'Traditional' surve...

Characterising viral #clearance #kinetics in acute #influenza

Abstract Pharmacometric assessment of antiviral efficacy in acute influenza informs treatment decisions and pandemic preparedness. We assessed natural viral clearance in untreated acute influenza to guide clinical trial design. Standardized duplicate oropharyngeal swabs were collected daily over 14 days from 80 untreated low-risk Thai adults , with viral densities measured using qPCR. We evaluated three models to describe viral clearance: exponential, bi-exponential, and growth-and-decay . The growth-and-decay model provided the best fit, but the exponential decay model was the most parsimonious. The median viral clearance half-life was 10.3 hours (interquartile range [IQR]: 6.8-15.4), varying by influenza type: 9.6 hours (IQR: 6.2-13.0) for influenza A and 14.0 (IQR: 10.3-19.3) hours for influenza B. Simulated trials using clearance parameters from the exponential decay model, showed that 120 patients per arm provide over 90% power to detect treatments accelerating viral clearance by ...

#Antiviral use and the effects of #drug #resistance on the #transmission dynamics of #influenza

Abstract The effectiveness of antivirals in mitigating influenza outbreaks depends on both their ability to reduce the number of infections and the risk of drug resistance. We extended a previously developed mathematical model to investigate the impact of mitigation strategies , including mono or combination antiviral treatment or chemoprophylaxis and vaccination , on influenza transmission dynamics. Our findings indicate that chemoprophylaxis is more effective than treatment in reducing influenza burden, except when the resistant strain has a high transmission rate, in which case chemoprophylaxis may trigger a resistance-driven secondary infection wave. Combination therapy considerably reduces resistance emergence with similar infection numbers as mono-therapy. Vaccination coverage of at least 80% is required to prevent outbreaks; otherwise, antivirals can contribute to outbreak control provided drug resistance emergence is low. This analysis could inform public health decision-making...

#US #CDC A(#H5N1) #Birdflu Response #Update March 19, 2025

{Excerpts} Recent updates Laboratory CDC completed serology testing on blood specimens from close contacts of a child with mild illness in San Francisco who was confirmed to be positive for avian influenza A(H5N1) virus, though, there were no known animal exposures associated with that case.  -- Serology testing was conducted to look for antibodies to influenza A(H5N1) virus in this child, which would indicate recent infection.  -- The child's blood was tested and found to have antibodies to avian influenza A(H5N1) virus.  -- None of the close contacts of the case in San Francisco who were tested had antibodies to avian influenza A(H5N1) virus, which supports the conclusion that none of these close contacts were infected , and that no person-to-person spread occurred among these close contacts.  -- These findings are reassuring. To date, human-to-human transmission of influenza A(H5) virus has not been identified in the United States. CDC has sequenced the virus from...

Safety and #effectiveness of MVA-BN #vaccination against #mpox in at-risk individuals in #Germany (SEMVAc and TEMVAc): a combined prospective and retrospective cohort study

Summary Background More than 115 000 cases of mpox have been confirmed since the onset of a global outbreak in 2022. In addition to global transmission of clade II monkeypox virus (MPXV), the recent spread of clade I has caused a Public Health Emergency of International Concern . The third-generation smallpox vaccine modified vaccinia Ankara–Bavarian Nordic (MVA-BN) was recommended for at-risk populations in 2022, despite a scarcity of data on safety and effectiveness against mpox. Methods We did a prospective, multicentre, observational study, enrolling men who have sex with men and transgender people aged 18 years or older with changing sexual partners in Germany (Safety and Effectiveness of MVA-BN Vaccination Against MPXV Infection [SEMVAc]) between July 7, 2022, and Dec 31, 2023, evaluating safety and reactogenicity of one and two doses of subcutaneous MVA-BN. Vaccine effectiveness was estimated using risk ratios from the Kaplan–Meier estimator in an emulated retrospective target t...

Large-scale computational #modelling of #H5 #influenza #variants against #HA1-neutralising #antibodies

Summary Background The United States Department of Agriculture has recently released reports that show samples collected from 2022 to 2025 of highly pathogenic avian influenza (H5N1) have been detected in mammals and birds . Up to February 2025, the United States Centres for Disease Control and Prevention reports that there have been 67 humans infected with H5N1 since 2024 with 1 death. The broader potential impact on human health remains unclear. Methods In this study, we computationally model 1804 protein complexes consisting of various H5 isolates from 1959 to 2024 against 11 haemagglutinin domain 1 (HA1)- neutralising antibodies . This was performed using AI-based protein folding and physics-based simulations of the antibody-antigen interactions. We analysed binding affinity changes over time and across various antibodies using multiple biochemical and biophysical binding metrics. Findings This study shows a trend of weakening binding affinity of existing antibodies against H5 isol...

Different #genetic #determinants for high #virulence, #transmission and #replication of high pathogenicity #H7N7 avian #influenza virus in #turkeys and #chickens

Abstract High pathogenicity (HP) avian influenza viruses (AIV) generally evolve from low pathogenicity (LP) precursors after transmission from wild birds to chickens (Gallus gallus domesticus) and turkeys (Meleagris gallopavo), causing severe economic losses worldwide. Turkeys are more susceptible to AIV infection than chickens and are considered potential bridging hosts that facilitate the emergence of HPAIV . Beyond the polybasic cleavage site (pCS) in hemagglutinin (HA), little is known about other virulence determinants of HPAIV in these species. In 2015, HPAIV H7N7 and its LP ancestor were isolated from the same chicken farm, which differed by 16 nonsynonymous mutations across all eight gene segments, in addition to the pCS. Here we identify the genetic determinants, including the pCS, that contributed to the HPAIV H7N7 virulence, transmission, replication, and tissue distribution in chickens and turkeys. Notably, the non-structural (NS1) or matrix (M) proteins ’ encoding segments...

#Baloxavir improves #disease #outcomes in #mice after intranasal or ocular #infection with #Influenza A virus #H5N1-contaminated cow’s #milk

Abstract Testing approved antivirals against A(H5N1) influenza viruses circulating in peridomestic species, including dairy cows , is critical to public health and pre-pandemic planning . It cannot be tested in humans due to A(H5N1) disease severity. Here, in mice, we demonstrate that US FDA-approved baloxavir treatment mediates improved disease outcomes ( survival and viral dissemination ) over oseltamivir after lethal intranasal and ocular challenge with A(H5N1)-contaminated cow milk. Source: Nature Microbiology,  https://www.nature.com/articles/s41564-025-01961-5 ____

Analyses of #phylogenetics, natural #selection, and #protein structure of clade 2.3.4.4b #H5N1 #Influenza A reveal that recent viral lineages have evolved promiscuity ...

Abstract H5N1 influenza has been circulating in birds from Eurasia and Africa for more than 146 years , but human infection has been sporadic. H5N1 (clade 2.3.4.4b) has recently infected hundreds of species of wild and domestic birds and mammals in North America . Furthermore, as of February 26, 2025, H5N1 has infected 70 humans in the United States , and one infection proved lethal . Furthermore, in attempts to control H5N1 in the United States, 10s of millions of egg-laying chickens have died or been culled . These efforts have led to very high egg prices in the United States. We have developed an analytical bioinformatics and genomics workflow to understand better how H5N1 is circulating in North America and adapting to new host species . Our workflow consists of: 1) Phylogenetic analyses of large viral sequence datasets to identify subclades of viral lineages causing the current outbreaks in humans and farm animals and closely related viral background lineages. 2) Next, we transfer...

3rd #meeting of #IHR(2005) #Emergency #Committee regarding the upsurge of #mpox 2024

The Director-General of the World Health Organization (WHO) is hereby transmitting the report of the third meeting of the International Health Regulations (2005) (IHR) Emergency Committee (Committee) regarding the upsurge of mpox 2024, held on Tuesday, 25 February 2025, from 12:00 to 17:00 CET . Concurring with the advice unanimously expressed by the Committee during the meeting, the WHO Director-General determined that the upsurge of mpox 2024 continues to meet the criteria of a public health emergency of international concern (PHEIC) and, accordingly, on 27 February 2025, issued temporary recommendations to States Parties. The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee. Proceedings of the meeting Sixteen (16) Members of, and two Advisors to, the International Health Regulations (2005) (IHR) Emergency Committee (Committee) were convened by teleconference, via Zoom, on Tuesday, 25 February 2025, from 12:00 to 17:00 CET...