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

 A poultry farm in Durrës Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6305

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Role of #antiviral #CD8+ T cell #immunity to #SARS-CoV-2 #infection and #vaccination

ABSTRACT

The COVID-19 pandemic has greatly enhanced our understanding of CD8+ T cell immunity and their role in natural infection and vaccine-induced protection. Rapid and early SARS-CoV-2-specific CD8+ T cell responses have been associated with efficient viral clearance and mild disease. Virus-specific CD8+ T cell responses can compensate for waning, morbidity-related, and iatrogenic reduction of humoral immunity. After infection or vaccination, SARS-CoV-2-specific memory CD8+ T cells are formed, which mount an efficient recall response in the event of breakthrough infection and help to protect from severe disease. Due to their breadth and ability to target mainly highly conserved epitopes, SARS-CoV-2-specific CD8+ T cells are also able to cross-recognize epitopes of viral variants, thus maintaining immunity even after the emergence of viral evolution. In some cases, however, CD8+ T cells may contribute to the pathogenesis of severe COVID-19. In particular, delayed and uncontrolled, e.g., nonspecific and hyperactivated, cytotoxic CD8+ T cell responses have been linked to poor COVID-19 outcomes. In this minireview, we summarize the tremendous knowledge about CD8+ T cell responses to SARS-CoV-2 infection and COVID-19 vaccination that has been gained over the past 5 years, while also highlighting the critical knowledge gaps that remain.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01350-24?af=R

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#Cluster of #community #deaths in Basankusu, Equateur- #DRC

Situation at a glance

On 9 February 2025, officials in the Democratic Republic of the Congo reported to regional health authorities a cluster of 24 unexplained community deaths in a single village in Ekoto health area, Basankusu health zone, Equateur province. 

As of 25 February, a total of 53 deaths have been reported, with the last death occurring on 22 February. 

Deaths have occurred in all age groups, but adolescents and young adults, particularly males, appeared to be disproportionately affected in the initial cluster reported. 

Disease progression appeared to be fast, with a median time from onset of symptoms to death of one day. 

Given the rapid decline in the incidence of reported deaths, their geographic clustering, the age profile of deaths and the rapid disease progression in the initial cluster, working hypotheses include chemical poisoning or a rapid onset bacterial meningitis cluster, on a background of malaria and other infectious illnesses endemic in the region. 

The definitive cause of illness remains undetermined, with initial samples testing negative for Ebola and Marburg viruses. 

Field investigations and additional laboratory testing are ongoing including but not limited to the cerebrospinal fluid testing and the toxicological analysis of environmental samples, including water and other samples to explore chemical causes. 

Local authorities began surveillance with a broad case definition including any individual with fever and at least one other symptom, to better understand disease patterns. 

A total of 1318 patients had symptoms meeting the working suspected case definition as of 25 February 2025. Approximately 50% of malaria tests performed on these cases tested positive for malaria, the cases identified through this enhanced surveillance therefore likely reflect the various febrile illnesses in the area. 

With the available information, WHO assesses the local public health risk as moderate, and the national and global public health risk as low.

Description of the situation

On 9 February 2025, an initial cluster of 24 community deaths of unknown origin were reported from a single village in Ekoto Health Area, Basankusu Health Zone, Equateur province, in the Democratic Republic of Congo. This triggered an investigation by the Ministry of Health, supported by WHO.

Enhanced surveillance was implemented shortly after, using a broad working case definition given the limited details on the clinical presentation, disease progression, demographic and other characteristics of the initial cluster. 

As of 25 February, a total of 53 deaths were reported. Deaths occurred across all age groups, but compared to the age and sex distribution of the population, appeared to disproportionately affect adolescents and young adult males, particularly in the initial cluster. This further pointed to an unusual event, as mortality from common causes in the area is usually highest among the elderly, and among young children (under five years) in a context of a high burden from infectious diseases, including malaria. The majority of deaths (50) occurred in the same village. Furthermore, the incidence of death rapidly declined following the initial cluster, suggesting this is not an event spreading in time or place.

The preliminary findings of the in-depth analysis revealed that the median time from symptom onset to death in the initial cluster was one day, with a mean time of two days. Symptoms reported include fever, chills, headaches, muscle aches, abdominal pains, diarrhea, sweating, dizziness, shortness of breath, agitation, and others.

(...)

Since the initiation of enhanced surveillance,1318 people reported symptoms meeting the working suspected case definition. However, given the broad nature of the case definition (fever and one other symptom from a range of general respiratory, gastrointestinal, or neurological symptoms), the trends in cases are difficult to interpret, and most likely reflect the prevalence of a range of febrile illnesses in the community. This is further suggested by the age distribution broadly mirroring that of the population, and the high malaria positivity among cases that were tested (approximately 50% positive on rapid diagnostic tests), which is not deemed unusual in an area where malaria is hyperendemic.

(...)

Although the cases were initially identified using a broad (i.e. non-specific) case definition, given the localized nature of the cluster of deaths, the steady decline in incidence of deaths, the demographic profile of deaths, and the rapid disease progression in the initial cluster, working hypotheses are that of a contamination by a chemical poisoning–be it accidental or deliberate—or possibly a rapid onset bacterial meningitis cluster.

Initial laboratory test results released on 13 February 2025 were negative for both Marburg and Ebola. Additional samples (blood, urine, oral, nasal) have been collected for further testing and investigations are ongoing. In addition, environmental samples–including water and other samples–are being collected to explore chemical causes, such as contamination by organophosphates.

The definitive cause of illness remains undetermined. Further testing and field investigations are ongoing to better characterize the cases and deaths.

Of note, this event in Basankusu follows a recent cluster of community deaths in the Bolomba Health Zone, which occurred from 10 to 27 January 2025. The epidemiological investigation documented 12 cases with eight deaths. Laboratory testing excluded Ebola and Marburg virus diseases and suggested that severe malaria could be the cause. While both Bolomba and Basankusu are located within Equateur Province, these health zones are separated by approximately 175 kilometers of difficult terrain including dense forests and poor road infrastructure; epidemiological investigation has found no evidence linking these distinct events.

Public health response

-- Coordination: A provincial rapid response team deployed to Basankusu and arrived on 16 February. The team was further supported by a WHO-MoH team from Kinshasa which arrived on 23 February.

-- Surveillance: WHO is supporting the MoH teams with field investigations, including the development of a structured epidemiological investigation protocol and the collection of additional samples for testing. As surveillance is being scaled up, the focus is on better understanding the characteristics of deaths. WHO is supporting health teams in their case investigations and active case search in the affected areas, including in communities, churches, and health facilities.

-- Laboratory: WHO is providing laboratory support to guide proper collection, storage, and transport of collected specimens to the National Institute of Biomedical Research (INRB) in Kinshasa, the biggest and most equipped laboratory in the country.

-- Logistics: WHO has provided essential medical supplies for management of usual infectious diseases and their symptoms, laboratory testing and infection prevention and control (IPC).

-- Risk communication and community engagement: Community engagement efforts are ongoing. Training sessions for community health workers are being conducted on how to identify people who meet the case definition and perform disease surveillance reporting. Awareness activities include community briefings and local radio broadcasts, as well as targeted discussion in villages on care-seeking behavior. 

-- Infection prevention and control: Systematic decontamination of isolation rooms at the General Hospital in Basankusu and Ekoto Health Center have been performed. On-site training of IPC supervisors and hygienists on chlorine solution preparation for decontamination have been conducted.

WHO risk assessment

Since the initial cluster of deaths was reported on 9 February 2025, there has been an overall downward trend in deaths. The most recent death was reported on 22 February 2025. Current epidemiological information suggests a localized event with a steady decline in incidence, not expanding in time and place. Given the clinical presentation of deaths and the speed from symptom onset to death in this unusual cluster, current differentials include a rapid onset bacterial meningitis cluster or a contamination by a chemical poisoning as key hypotheses in a context of high incidence of other common infectious diseases in the areas, particularly malaria.

Operational challenges related to this event involve the isolation of Basankusu and resulting logistical barriers, as it is located in a forested region, approximately 450 kilometers from the nearest major city of Mbandaka and has poor infrastructure. The remoteness of Basankusu has hindered the timeliness of the initial investigation and response activities and poses challenges to laboratory testing. Samples must be collected, stored, and shipped long distances to a larger city with laboratory testing capacity (either Mbandaka or Kinshasa), introducing delays in diagnosis. Access to care is another key challenge, as the region lacks robust healthcare services, and the region’s poor infrastructure makes travel to neighboring health zones difficult, leading to delays in treatment.  

The province faces a severe urban water crisis with only 5% of its urban population having access to drinking water. The water network suffers frequent leaks and has never been rehabilitated. Many households rely on unregulated private water sources such as wells, springs and streams which pose contamination risks.

With ongoing investigations and given that the causative agent of the cluster is not yet determined, there remains a level of risk attributed to the event. As such, the overall public health risk level to the affected communities is assessed as moderate.

At the national level, however, the risk is considered low due to the localized nature of the event and apparent decreasing incidence. Similarly, at the regional and global levels, the risk is low at this time. 

WHO advice

To reduce the impact of the event in the Basankusu health zone, WHO advises the following measures:  

-- Careful characterization of the clinical syndrome and outcomes as well as an improved case definition based on collected information to better understand the outbreak.

-- Enhanced surveillance focusing specifically on deaths, and severe febrile cases or severe cases of unexplained illness, with better clinical characterization to reinforce early case detection and reporting.

-- Continued laboratory testing and environmental assessments (including water sources) to evaluate the current hypotheses of meningitis and/or a toxin/poisoning event, particularly among severe cases and deaths.

-- Risk communication and community engagement to increase public awareness about the event, explaining symptoms and the importance of seeking immediate care. It is also critical to address any potential misinformation about the outbreak circulating in the community.

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON557

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

 A poultry farm in Sachsen Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6301

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

A whopper swan was found dead. It was sent to the Swedish Veterinary Agency (formerly National Veterinary Institute) for laboratory analysis as part of the national surveillance program for avian influenza.

Source: WOAH, https://wahis.woah.org/#/in-review/6299

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A #WHO global #framework to guide #investigations into origins of potentially #epidemic and #pandemic #pathogens

{Summary}

In outbreak situations involving a novel pathogen timely and coordinated response is crucial. The WHO Scientific Advisory Group for the Origins of Novel Pathogens recently released a global framework to guide future scientific investigations into the origin of emerging pathogens.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-57218-6

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Identification of Aminoacid #Residues Responsible for Differential #Replication & #Pathogenicity of Avian #Influenza Virus #H5N1 Isolated from #Human & #Cattle in #Texas

Abstract

Highly pathogenic avian influenza viruses (HPAIV) pose a serious public health concern. In March 2024, a first-time outbreak of HPAIV H5N1 in dairy cattle herds was reported in the United States (US). Since then, the virus has continued to spread in cattle herds and spilt over into humans. We recently showed that the first human isolate reported in the US in Texas (HPhTX) from a dairy worker in an affected cattle farm has enhanced replication kinetics and pathogenicity in mice compared to a closely related bovine isolate (HPbTX). However, the molecular determinants of differential pathogenicity have not yet been identified. Herein, we show that HPhTX has enhanced polymerase activity, compared with HPbTX, in human cells and that the polymerase basic 2 (PB2) protein is the main factor responsible for this difference. Through single and combined site-directed mutagenesis and swapping the three amino acids different between HPhTX and HPbTX, we found that PB2 mutation E627K is the major contributor to the enhanced polymerase activity of HPhTX. E362G substitution in HPhTX PB2 affected the polymerase, although to a lesser extent than E627K. Moreover, M631L mutation in HPhTX PB2 enhanced polymerase activity. Rescue of a loss-of-function recombinant HPhTX (rHPhTX) containing mutations at residues 627 and 362, alone or in combination, revealed a contribution of PB2 E362G and K627E in morbidity, mortality, and viral replication as compared to rHPhTX wild-type (WT), and significantly reduced viral pathogenicity to levels comparable to rHPbTX WT. These findings indicate that HPAIV H5N1 of cattle origin isolated from the first human case has post-transmission amino acid changes that increase viral replication in human cells and pathogenicity in mice.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.01.640810v1

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#Portimine A #toxin causes #skin #inflammation through ZAKα-dependent NLRP1 inflammasome activation

Abstract

In 2020–2021, a “mysterious illness” struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal the presence of the marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, we show that the toxin PortimineA, strongly enriched in environmental samples, impedes ribosome function in human keratinocytes, which subsequently activates the stress kinases ZAKα and P38 and promotes the nucleation of the human NLRP1 inflammasome, leading to the release of IL-1β/IL-18 pro-inflammatory cytokines and cell death. Furthermore, cell-based models highlight that naturally occurring mutations in the P38-targeted sites of human NLRP1 are unable to respond to PortimineA exposure. Finally, the development and use of human organotypic skins and zebrafish models of PortimineA exposure demonstrate that the ZAKα-NLRP1 axis drives skin necrosis and inflammation. Our results exemplify the threats to human health caused by emerging environmental toxins and identify ZAKα and NRLP1 as important pharmacological targets to mitigate PortimineA toxicity.

Source: EMBO Molecular Medicine, https://www.embopress.org/doi/full/10.1038/s44321-025-00197-4

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    Wastewater surveillance overcomes socio-economic limitations of laboratory-based surveillance when monitoring disease transmission: The South African experience during the COVID-19 pandemic.
    PLoS One. 2025;20:e0311332.
    PubMed         Abstract available
    
    
31. BALSOM AA, Dube L, Gordon JL
    What women want to hear: the helpful and unhelpful comments reported by women struggling with infertility amidst the COVID-19 pandemic.
    PLoS One. 2025;20:e0318921.
    PubMed         Abstract available
    
    
32. OTAKI F, Ho SB, Nair B, AlGurg R, et al
    Effects of building resilience skills among undergraduate medical students in a multi-cultural, multi-ethnic setting in the United Arab Emirates: A convergent mixed methods study.
    PLoS One. 2025;20:e0308774.
    PubMed         Abstract available
    
    
33. O'BRIEN KK, Brown DA, McDuff K, St Clair-Sullivan N, et al
    Episodic disability framework in the context of Long COVID: Findings from a community-engaged international qualitative study.
    PLoS One. 2025;20:e0305187.
    PubMed         Abstract available
    
    
34. GHEZZAWI M, Fahme S, Al Sabbagh R, Naalbandian S, et al
    Impact of the COVID-19 pandemic on women in the workplace in the Middle East and North Africa: A scoping review protocol.
    PLoS One. 2025;20:e0312037.
    PubMed         Abstract available
    
    
35. NUGENT JR, Wood MS, Liu L, Bullick T, et al
    SARS-CoV-2 Omicron subvariant genomic variation associations with immune evasion in Northern California: A retrospective cohort study.
    PLoS One. 2025;20:e0319218.
    PubMed         Abstract available
    
    

    
    Proc Natl Acad Sci U S A

36. SCHNYDER SK, Molina JJ, Yamamoto R, Turner MS, et al
    Understanding Nash epidemics.
    Proc Natl Acad Sci U S A. 2025;122:e2409362122.
    PubMed         Abstract available
    
    

    
    Vaccine

37. SHEERAH HA, Al-Jedai AH, Al-Jerian NA, Al-Otaiby MA, et al
    COVID-19 and influenza hospitalizations and the role of COVID-19 vaccination in the post-pandemic period: A cross-sectional study from Saudi Arabia.
    Vaccine. 2025;52:126937.
    PubMed         Abstract available
    
    
38. FARAH Z, Bazant ES, Basha I, Saleh N, et al
    Determinants of seasonal influenza vaccination uptake, intention and recommendations among Lebanese physicians.
    Vaccine. 2025;52:126890.
    PubMed         Abstract available
    
    
39. YE Q, Xiao Z, Bai C, Yao H, et al
    Unveiling the multi-characteristic potential of hyper-productive suspension MDCK cells for advanced influenza A virus propagation.
    Vaccine. 2025;52:126900.
    PubMed         Abstract available
    
    
40. DARWAR R, Huang X, Abayeneh A, Alemayehu Beshah S, et al
    Costing approaches for vaccine-preventable disease surveillance: Lessons from Ethiopia and Nepal.
    Vaccine. 2025;50:126776.
    PubMed         Abstract available
    
    
41. COTUGNO N, Sanna M, Amodio D, Morrocchi E, et al
    Pre-vaccination immune markers predict response to BNT162b2 mRNA vaccine in vulnerable groups - The CONVERS project, report from a pediatric tertiary hospital.
    Vaccine. 2025;49:126778.
    PubMed         Abstract available
    
    
42. SHARMA A, Kerkhoff AD, Haambokoma M, Shamoya B, et al
    Intention to receive new vaccines post-COVID-19 pandemic among adults and health workers in Lusaka, Zambia.
    Vaccine. 2025;50:126846.
    PubMed         Abstract available
    
    
43. CAPAO A, Araujo MF, Tort LFL, Toledo TS, et al
    Impact in the humoral and cellular immune response to SARS-CoV-2 variants after primary vaccination with AZD1222/COVISHIELD protocol in healthy adults.
    Vaccine. 2025;50:126785.
    PubMed         Abstract available
    
    
44. SHINO MY, Ibarrondo FJ, Yang OO
    SARS-CoV-2 spike antibody levels in lung transplantation recipients versus the spectrum in non-immunocompromised persons.
    Vaccine. 2025;50:126851.
    PubMed         Abstract available
    
    
45. FU Y, Xu Z, Wang Q, Zhang J, et al
    Effectiveness and coverage of COVID-19 vaccination among the infection-naive population: A community-based retrospective cohort study in China.
    Vaccine. 2025;50:126836.
    PubMed         Abstract available
    
    
46. VAHORA MS, Leao O, da Silveira MF, Domingues MR, et al
    Impacts of vaccination, school attendance, and nutrition on SARS-CoV-2 antibody titer in a prospective birth cohort in Brazil.
    Vaccine. 2025;49:126838.
    PubMed         Abstract available
    
    
47. MCCLYMONT E, Wong JMH, Forward L, Blitz S, et al
    Acceptance and preference between respiratory syncytial virus vaccination during pregnancy and infant monoclonal antibody among pregnant and postpartum persons in Canada.
    Vaccine. 2025;50:126818.
    PubMed         Abstract available
    
    
48. KANG HS, Kim SY, De Gagne JC, Chae SM, et al
    Pregnant women's experiences of and attitudes toward COVID-19 vaccination: A qualitative descriptive study.
    Vaccine. 2025;50:126835.
    PubMed         Abstract available
    
    
49. LAO G, Feng J, Wu L, Su W, et al
    Development of a genetically modified full-length human respiratory syncytial virus preF protein vaccine.
    Vaccine. 2025;49:126799.
    PubMed         Abstract available
    
    
50. ITO S, Tsuchida N, Kusunoki S, Kaneko Y, et al
    Safety comparison between Pfizer BNT162b2, Moderna mRNA-1273, and AstraZeneca AZD1222 in a Nationwide prospective cohort survey at the beginning of the severe acute respiratory syndrome coronavirus 2 vaccination in Japan.
    Vaccine. 2025;49:126754.
    PubMed         Abstract available
    
    
51. WIEGAND RE, Devine O, Wallace M, Ortega-Sanchez IR, et al
    Estimating COVID-19 associated hospitalizations, ICU admissions, and in-hospital deaths averted in the United States by 2023-2024 COVID-19 vaccination: A conditional probability, causal inference, and multiplier-based approach.
    Vaccine. 2025;49:126808.
    PubMed         Abstract available
    
    
52. JI C, Senthinathan A, Apajee J, Dubey V, et al
    Impact of the COVID-19 pandemic on routine immunization coverage of children and teenagers in Ontario, Canada.
    Vaccine. 2025;49:126811.
    PubMed         Abstract available
    
    
53. YILMAZ IC, Ipekoglu EM, Golcuklu BS, Bildik T, et al
    A phase I/II study of CpG/alum-adjuvanted mammalian-derived quadruple antigen carrying virus-like particle COVID-19 vaccine.
    Vaccine. 2025;49:126787.
    PubMed         Abstract available
    
    
54. GRAILEY K, Crespo RF, Woldmann L, Chisambi M, et al
    Implementing behavioural science-informed letter interventions to increase COVID-19 vaccination uptake in London residents. A difference-in-difference study in London, United Kingdom.
    Vaccine. 2025;49:126781.
    PubMed         Abstract available
    
    
55. GSCHWEND MH, Marchese AM, Poelaert D, Warren B, et al
    Efficacy, immunogenicity, and safety of the Novavax COVID-19 vaccine in immunocompromised patients: A targeted literature review.
    Vaccine. 2025;49:126777.
    PubMed         Abstract available
    
    
56. MCGOLDRICK M, Truong TBQ, Campa C, Ali M, et al
    How to accelerate the supply of vaccines to all populations worldwide? Part III: Reflections after the pandemic.
    Vaccine. 2025;49:126782.
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57. KAN AKC, Mak HWF, Chiang V, Yim JSH, et al
    Leveraging COVID-19 vaccine allergy evaluations with coincident drug allergy delabelling: Effectiveness and impact on quality of life.
    Vaccine. 2025;50:126849.
    PubMed         Abstract available
    
    
58. DOUA J, Ndembi N, Auerbach J, Kaseya J, et al
    Advancing local manufacturing capacities for vaccines within Africa - Opportunities, priorities and challenges.
    Vaccine. 2025;50:126829.
    PubMed         Abstract available
    
    
59. HONDA-OKUBO Y, Sajkov D, Wauchope B, Turner JV, et al
    Immunogenicity and safety study of a single dose of SpikoGen(R) vaccine as a heterologous or homologous intramuscular booster following a primary course of mRNA, adenoviral vector or recombinant protein COVID-19 vaccine in ambulatory adults.
    Vaccine. 2025;49:126744.
    PubMed         Abstract available
    
    

    
    Virology

60. HARADA R, Hiono T, Igarashi M, Kobayashi D, et al
    Altered receptor-binding specificity of gull-adapted H13 avian influenza viruses corresponds to their unique host preferences.
    Virology. 2025;605:110460.
    PubMed         Abstract available

 

Molecular #patterns of #matrix protein 1 (M1): A strong predictor of adaptive #evolution in #H9N2 avian #influenza viruses

Significance

The dominance of the H9N2 subtype of avian influenza virus (AIV) within the influenza A virus family has raised questions regarding the factors influencing its epidemiological dominance. This study concentrates on the role of five major evolutionary patterns of the matrix protein M1 in the replication and transmission of H9N2 AIVs. The findings indicate a strong correlation between the epidemiological dominance of H9N2 AIVs and the specific M1 patterns, particularly M1P5. It highlights the significance of genetic patterns in M1 for understanding the adaptive differences and turnover of epidemiological dominant H9N2 AIVs.

Abstract

The H9N2 subtype of avian influenza virus (AIV) emerges as a significant member of the influenza A virus family. However, the varying degrees of epidemiological dominance among different lineages or clades of H9N2 AIVs have not been fully clarified. The matrix protein M1, a key structural component of the virion, plays a crucial role in maintaining the viral structure and lifecycle. To elucidate the intrinsic relationship between the genetic patterns of M1 and the adaptive dynamics of H9N2 AIVs, this study focused on the five major evolutionary patterns of M1 and conducted in vitro and in vivo investigations from the perspectives of vRNP release after viral uncoating, polymerase activity, mRNA and vRNA levels, the nuclear export of vRNPs, plasma membrane–binding capacity, proliferation capacity, growth competitiveness, and transmission potential. The results revealed a strong correlation between the epidemiological dominance of H9N2 AIVs and the specific patterns of M1, with M1P5 standing out as particularly significant. This finding highlights the pivotal influence of the M1 gene patterns on the replication and transmission dynamics of H9N2 AIVs, thereby offering valuable insights into the mechanisms driving differences in adaptive evolution and shifts in epidemiological dominance within the H9N2 AIV population.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2423983122

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Dynamics of natural #selection preceding #human viral #epidemics and #pandemics.

Abstract

Using a phylogenetic framework to characterize natural selection, we investigate the hypothesis that zoonotic viruses require adaptation prior to zoonosis to sustain human-to-human transmission. Examining the zoonotic emergence of Ebola virus, Marburg virus, influenza A virus, SARS-CoV, and SARS-CoV-2, we find no evidence of a change in the intensity of natural selection immediately prior to a host switch, compared with typical selection within reservoir hosts. We conclude that extensive pre-zoonotic adaptation is not necessary for human-to-human transmission of zoonotic viruses. In contrast, the reemergence of H1N1 influenza A virus in 1977 showed a change in selection, consistent with the hypothesis of passage in a laboratory setting prior to its reintroduction into the human population, purportedly during a vaccine trial. Holistic phylogenetic analysis of selection regimes can be used to detect evolutionary signals of host switching or laboratory passage, providing insight into the circumstances of past and future viral emergence.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.26.640439v1

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Phylogenetic #discordance cannot identify #genomic #reassortment events: a case study with the avian #influenza virus #H5Nx

Abstract

Recombination plays a central role in the evolution of the RNA virus genome, as it allows the exchange of genetic material between different viral lineages. Reassortment is a form of recombination specific to viruses with segmented genomes that involves the exchange of entire segments between lineages. This process has played a significant role in the adaptation and spread of influenza viruses, where novel combinations of genomic segments are produced from divergent lineages (i.e., antigenic shift). In this study, we investigated reassortment events in a representative sample of n = 11, 765 complete genomes of H5Nx influenza A viruses from avian hosts. Using tanglegrams and subtree-prune-regraft (SPR) methods to quantify discordance between segment trees, we found evidence of widespread reassortment among these genomes that is consistent with previous studies. However, we obtained the comparable numbers of reassortment events when applying the same methods to sequence data simulated in the complete absence of any reassortment. This outcome indicates a high false positive rate in identifying reassortment events due to uncertainty in phylogenetic reconstruction. There was also no significant difference between SPR events inferred from real data versus simulated false positives with respect to subtree size, or the distance between prune and regraft points in the reference tree. Although there is no doubt that reassorment has played a significant role in the origin of new pandemic strains of influenza viruses, these results imply that previous reports of extensive reassortment in the avian influenza virus literature should be interpreted with caution.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.24.639875v1

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Elucidating the Characteristics and #Clonal Evolutionary #Trajectory of #Influenza #Neuraminidase Broadly Reactive B Cell

Abstract

Influenza virus neuraminidase (NA) is receiving increasing attention as a target for universal flu vaccines. Several broad NA inhibition monoclonal antibodies (BImAbs) targeting the highly conserved enzymatic pocket have been previously described. However, the molecular characteristics, clonal evolutionary trajectory, and B cell sources of BImAbs remain poorly understood. Here, using NA-mutant probes, we comprehensively profiled the immune signatures of NA-specific memory B cells (MBCs) from a healthy individual with NA cross-inhibition activity. From the NA-specific MBC repertoires, we identified a series of NA BImAbs with molecular features characterized by long HCDR3 regions with an xxxDRxxx motif, which exhibited broad inhibition against diverse influenza NAs. Clonal lineage tracing revealed that these BImAbs followed a clonal evolutionary trajectory encompassing classical MBC (cMBC) and atypical MBC (aMBC). Both cMBC- and aMBC-derived NA BImAbs displayed similar inhibitory activity against the influenza NAs. These findings enhance our understanding of the development of NA BImAbs and provide a foundation for the rational design of NA-based universal flu vaccines.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.23.639775v1

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#USA, #NJ: #H5N1 Highly Pathogenic Avian #Influenza Confirmed in New Jersey Cats {DoH}

TRENTON, NJ - The first feline case of H5 Highly Pathogenic Avian Influenza (HPAI or “bird flu”) in New Jersey has been confirmed in a feral cat from Hunterdon County. 

The case was confirmed by the United States Department of Agriculture (USDA) National Veterinary Services Laboratory, and follows previous national reports of confirmed feline cases in other states.  

The cat developed severe disease, including neurologic signs, and was humanely euthanized. 

Other cats on the same property were also reported ill, and one additional indoor-outdoor cat was subsequently confirmed positive for H5 HPAI. Other tests are still pending, and the investigation is ongoing.

The overall public health risk remains low at this time. While H5 HPAI has been detected in humans in the U.S. – primarily in individuals with close contact with infected poultry or dairy cattle – there have been no human cases reported in New Jersey, and none of the cases across the country are known to have resulted from exposure to an infected cat.

Local health officials are working closely with the New Jersey Department of Health in conducting follow up and symptom monitoring on individuals that have been in contact with these cats. All exposed individuals are currently asymptomatic. 

Residents who have had close, unprotected contact with a cat or other animal infected with H5 HPAI should contact their local health department and monitor themselves for symptoms for 10 days following their last exposure.

“While the risk of H5 infection to the general population remains low at this time, it is important for people to learn more about the situation and take steps to avoid potential infection through exposure to animals, including feral cats,” said New Jersey Health Commissioner Kaitlan Baston, MD, MSc, DFASAM. “We continue to work with state and federal partners to monitor the spread of this virus and provide public information on mitigating the risks.”

Cats are particularly susceptible to H5 HPAI and often experience severe disease and high mortality when infected. Potential exposure sources of H5 HPAI for cats include consuming raw (unpasteurized) milk or raw/undercooked meat contaminated with the virus, infected birds or other animals and their environments, or exposure to contaminated clothing or items (fomites) worn or used on affected premises.

The cats tied to this incident in Hunterdon County had no known reported exposures to infected poultry, livestock, or consumption of raw (unpasteurized) milk or meat, but did roam freely outdoors, so exposure to wild birds or other animals is unknown.

Clinical signs in cats can include:

-- General signs: Loss of appetite, fever, lethargy

-- Respiratory signs: Discharge from the eyes and mouth, sneezing, coughing, difficulty breathing

-- Neurologic signs: Seizures, circling, wobbling gait, blindness.

New Jersey residents should contact their veterinarian immediately if they are concerned that their cat may have H5 bird flu. Anyone who suspects a possible exposure or who has H5 HPAI concerns about their cat should contact their veterinarian prior to bringing the cat in to be seen so that the veterinarian can take the necessary precautions to prevent spread of disease. Residents who observe a sick stray or feral cat should contact their local animal control for assistance.

Veterinarians who suspect H5 HPAI in a cat should follow CDC recommendations to help protect themselves and prevent exposures, including wearing personal protective equipment (PPE) when handling the cats. All suspect feline cases should be reported to the New Jersey Department of Health Communicable Disease Service at 609-826-4872 or zoonoticrn@doh.nj.gov. Testing for suspect feline cases is available at the New Jersey Animal Health Diagnostic Laboratory, a member of the USDA’s National Animal Health Laboratory Network. Guidance for veterinarians on specimen collection and submission can be found here.

New Jersey residents can find additional information and recommendations on ways to help prevent H5 bird flu infection in cats from the American Veterinary Medical Association.

Additionally, cat owners can take the following steps to help protect their pets:

-- Do not feed cats raw (unpasteurized) milk or dairy products, and avoid feeding any raw or undercooked meat treats or diets.

-- Keep cats indoors to prevent exposure to birds and other wildlife.

-- Keep cats away from livestock, poultry, and their environments.

-- Avoid contact with sick or dead birds and other wildlife yourself.

-- Thoroughly wash your hands after handling your cat and after any encounters with poultry, livestock, or wild birds and other animals.

-- Change your clothes and shoes, and thoroughly wash any exposed skin, after interacting with sick or dead animals that may harbor the H5N1 virus, and before interacting with your cat.

-- Contact a veterinarian if you notice signs of H5 HPAI or think your cat might have been exposed to the virus.

“The H5N1 virus has the ability to move from one species to another,” New Jersey Agriculture Secretary Ed Wengryn said. "That is why we have worked closely with our poultry and dairy industries on biosecurity measures to prevent exposure by wild animals, and feral cats are another example of the risks to livestock and humans.”

“Despite low risk to the public, avian influenza is believed to be present in wild birds in all of New Jersey’s counties,” Environmental Protection Commissioner Shawn M. LaTourette said. “The Department of Environmental Protection continues to work closely with state and federal partners to track and respond to avian flu in wild birds and keep the public informed.” 

NJDOH continues to work in collaboration with the NJ Department of Environmental Protection (NJDEP) and the NJ Department of Agriculture (NJDA) to monitor occurrences of H5N1 Avian Influenza and its impact in the State.

If you find sick or dead wild birds, do not handle them. Contact the NJDEP’s Fish and Wildlife hotline at 1-877-WARNDEP. 

To report sick or dead poultry, do not handle them. Contact the NJDA Division of Animal Health at 609-671-6400. 

Additional Resources

- NJ.gov - H5N1 Information: nj.gov/H5N1

- NJ Department of Health, Communicable Disease Service - Novel Influenza: nj.gov/health/cd/topics/novel_flu.shtml

- NJ Department of Agriculture, Animal Health Diagnostic Laboratory - Contact Information: nj.gov/agriculture/ahdl/contact

- Centers for Disease Control and Prevention - Avian Influenza (Bird Flu): cdc.gov/bird-flu/hcp/animals/index.html

- American Veterinary Medical Association - Avian influenza A (H5N1) in cats: avma.org/resources-tools/animal-health-and-welfare/animal-health/avian-influenza/avian-influenza-h5n1-cats

Source: Department of Health, https://www.nj.gov/health/news/2025/approved/20250228a.shtml

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

This is a farm with pheasants for game restocking. The birds are being euthanized 27 February  A protection zone (3km) and a surveillance zone (10 km) have been put in place around the infected farm and all other restrictions and necessary measures according to Regulation (EU) 2016/429 and (EU) 2020/687.

Source: WOAH, https://wahis.woah.org/#/in-review/6297

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#Recommendations announced for #influenza #vaccine #composition for the 2025-2026 northern hemisphere influenza season

The World Health Organization (WHO) today announced the recommendations for the viral composition of influenza vaccines for the 2025-2026 influenza season in the northern hemisphere. 

The announcement was made at an information session at the end of a 4-day meeting on the Composition of Influenza Virus Vaccines, a meeting that is held twice annually. 

WHO organizes these consultations with an advisory group of experts gathered from WHO Collaborating Centres and WHO Essential Regulatory Laboratories to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS). 

The recommendations issued are used by the national vaccine regulatory agencies and pharmaceutical companies to develop, produce, and license influenza vaccines for the following influenza season. 

The periodic update of viruses contained in influenza vaccines is necessary for the vaccines to be effective due to the constant evolving nature of influenza viruses, including those circulating and infecting humans.

The WHO recommends that trivalent vaccines for use in the 2025-2026 northern hemisphere influenza season contain the following: 

-- Egg-based vaccines

- an A/Victoria/4897/2022 (H1N1)pdm09-like virus;

- an A/Croatia/10136RV/2023 (H3N2)-like virus; and

- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus.

-- Cell culture-, recombinant protein- or nucleic acid-based vaccines

- an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;

- an A/District of Columbia/27/2023 (H3N2)-like virus; and

- a B/Austria/1359417/2021 (B/Victoria lineage)-like virus. 

The recommendation for the B/Yamagata lineage component of quadrivalent influenza vaccines remains unchanged from previous recommendations:

- a B/Phuket/3073/2013 (B/Yamagata lineage)-like virus.

Source: World Health Organization, https://www.who.int/news/item/28-02-2025-recommendations-announced-for-influenza-vaccine-composition-for-the-2025-2026-northern-hemisphere-influenza-season

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {Feb. 28 '25}

 

{Excerpt}

Time Period: February 16 - February 22, 2025

-- H5 Detection: 10 sites (2.6%)

-- No Detection: 379 sites (97.4%)

-- No samples in last week: 75 sites

(...)

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

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A replicating #recombinant #VSV #model for dairy #cattle #H5N1 #influenza virus glycoprotein #evolution

Abstract

A panzootic of highly pathogenic avian influenza (HPAI) H5N1 viruses from clade 2.3.4.4b has triggered a multistate outbreak in United States dairy cattle and an unknown number of human infections. HPAI viruses are handled in specialized biocontainment facilities. Ethical considerations limit certain experimental evolution experiments aimed at assessing viral resistance to potential therapeutics. We have developed a replicating recombinant vesicular stomatitis virus (rVSV) where we replaced its glycoprotein with the hemagglutinin (HA) and neuraminidase (NA) genes of a 2.3.4.4b H5N1 virus (rVSV-H5N1dc2024), which is free of these constraints. This virus grows to high titers and encodes a fluorescent reporter to track infection. We demonstrate the utility of rVSV-H5N1dc2024 in neutralization experiments, evaluating antibody escape and characterization of resistance mutations to NA inhibitors. rVSV-H5N1dc2024 or similar viruses may accelerate efforts to develop and evaluate interventions against this emerging threat to human and animal health.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.27.640582v1

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Novel #human #coronavirus in an #infant #patient with #pneumonia, Republic of #Korea

ABSTRACT

Coronaviruses (CoVs) pose a significant threat to public health, causing a wide spectrum of clinical manifestations and outcomes. Beyond precipitating global outbreaks, Human CoVs (HCoVs) are frequently found among patients with respiratory infections. To date, limited attention has been directed towards alphacoronaviruses due to their low prevalence and fatality rates. Nasal swab and serum samples were collected from a paediatric patient, and an epidemiological survey was conducted. Retrospective surveillance investigated the molecular prevalence of CoV in 880 rodents collected in the Republic of Korea (ROK) from 2018 to 2022. Next-generation sequencing (NGS) and phylogenetic analyses characterized the novel HCoV and closely related CoVs harboured by Apodemus spp. On 15 December 2022, a 103-day-old infant was admitted with fever, cough, sputum production, and rhinorrhea, diagnosed with human parainfluenza virus 1 (HPIV-1) and rhinovirus co-infection. Elevated AST/ALT levels indicated transient liver dysfunction on the fourth day of hospitalization. Metagenomic NGS (mNGS) identified a novel HCoV in nasal swab and serum samples. Retrospective rodent surveillance and phylogenetic analyses showed the novel HCoV was closely related to alphacoronaviruses carried by Apodemus spp. in the ROK and China. This case highlights the potential of mNGS to identify emerging pathogens and raises awareness of possible extra-respiratory manifestations, such as transient liver dysfunction, associated with novel HCoVs. While the liver injury in this case may be attributable to the novel HCoV, further research is necessary to elucidate its clinical significance, epidemiological prevalence, and zoonotic origins.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2466705

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