Thursday, July 17, 2025

Multidisciplinary #Tracking of Highly Pathogenic Avian #Influenza #H5N1 #Outbreak in Griffon #Vultures, Southern #Europe, 2022

Abstract

Since 2021, highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus has affected wild bird populations globally. Griffon vultures (Gyps fulvus), a species hitherto considered unexposed, experienced an HPAI H5N1 outbreak in 2022 in southern Europe, leading to moderate mortality and reduced breeding success. The integration of virological, serologic, phylogenetic, and ecologic data revealed a short yet intense viral circulation and a probable common source of infection. The dissemination across Spain and France was likely caused by frequent interpopulation movements of birds. This integrated overview of the 2022 HPAI outbreak in vultures provides novel insights into the role of large-scale movements of wild birds in the spread of such disease. Understanding the epidemiologic dynamics of HPAI H5N1 in these scavenger species is crucial because the birds play vital roles in ecosystem functioning. Their susceptibility to this virus highlights potential broader ecologic effects of the ongoing outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/24-1456_article

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Laboratory #Diagnosis of #Hendra and #Nipah: Two Emerging Zoonotic Diseases with One Health Significance

Abstract

Hendra virus (HeV) and Nipah virus (NiV) are two highly pathogenic RNA viruses with zoonotic potential, which can cause severe diseases with high mortality rates (50–100%) in humans and animals. Given this context, these viruses are classified as Biosafety Level 4 (BSL-4) pathogens, thus limiting research studies. Despite the high case fatalities, there are currently no human vaccines available for either virus, owing in part to the limitations in research and hesitancy in funding. In the absence of widespread vaccination, diagnostic tests are crucial for the rapid identification of cases and disease surveillance. This review synthesizes current knowledge on the epidemiology, transmission dynamics, and pathogenesis of NiV and HeV to contextualize a detailed assessment of the available diagnostic tools. We examined molecular and serological assays, including RT-PCR, ELISA, and LAMP, highlighting sample sources, detection windows, and performance. Diagnostic considerations across human and animal hosts are discussed, with emphasis on outbreak applicability and field-readiness, given the need for diagnostic assays that are suitable for use in low-income areas. Further development of diagnostic assays, including isothermal amplification tests and other next-generation approaches, is recommended to fill the gap in rapid, point-of-care diagnostics.

Source: Viruses, https://www.mdpi.com/1999-4915/17/7/1003

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Anthropozoonotic #spillovers reveal sustained long-term cryptic #circulation of #SARS-CoV-2 within and between #Lithuanian #mink farms

Abstract

Several studies have documented reverse zoonotic transmission of SARS-CoV-2, including in farmed mink which are susceptible to human respiratory viruses and are known for serving as a reservoir capable of generating new virus variants in densely populated farms. Here, we present the results of a genomic investigation launched in response to detected human infections with mink-origin SARS-CoV-2 lineages, and show evidence of at least 14 high-confidence introductions of SARS-CoV-2 from humans into farmed mink in Lithuania where sustained transmission in farmed mink lasted up to a year. We estimated the most likely timeframes for these introductions encompassing at least six SARS-CoV-2 lineages, some of which were already extinct in humans, with Bayesian phylogenetic and molecular clock analyses. This study highlights the public health risks posed by fur farms and underscores that passive genomic surveillance systems are ineffective without the active involvement and expertise of responsible institutions.


Competing Interest Statement

The authors have declared no competing interest.


Funding Statement

Gytis Dudas was supported by EMBO installation grant EMBO-IG-5305-2023.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.15.25331253v1

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Wednesday, July 16, 2025

Detection of low pre-existing humoral #immunity against #influenza virus #H5N1 clade 2.3.4.4b in unexposed individuals

Abstract

The spill-over of Influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of a human H5N1 pandemic. Given the impact of pre-existing immunity on the course and severity of viral infections, we comprehensively assessed the humoral immunity against the H5N1 A/Texas/37/2024 isolate in H5N1-naive individuals. To this end, we performed complementary binding and neutralization assays on 66 subjects and ranked activities among a panel of 76 influenza A virus isolates. We detected low but distinct cross-neutralizing titers against A/Texas/37/2024 with a 3.9 to 15.6-fold reduction compared to selected H1N1 or H3N2 strains. By cloning and evaluating 136 monoclonal antibodies from memory B cells, we identified potent A/Texas/37/2024-neutralizing monoclonal antibodies in five out of six investigated individuals. These antibodies cross-neutralize H1, compete with antibodies targeting the HA stem, and protect mice from lethal H5N1 challenge. Our findings demonstrate partial pre-existing humoral immunity to A/Texas/37/2024 in H5N1-naive individuals.


Competing Interest Statement

DR, MM, CK, FK, and ML are members of the non-profit Center for Predictive Analysis of Viral Evolution (Previr). LG, HG, CK and FK are inventors on patent applications on virus neutralizing antibodies filed by the University of Cologne and have received payments from the University of Cologne for licensed patents.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.22.634277v2

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Development of #DNA and #mRNA-LNP #vaccines against an #H5N1 clade 2.3.4.4b #influenza virus

ABSTRACT

Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States. While nucleic acid-based vaccines such as mRNA-lipid nanoparticles (LNPs) have several potential advantages during a viral epidemic compared to traditional seasonal influenza vaccines, their utility and efficacy against H5N1 viruses remain incompletely defined. Here, we developed novel DNA- and mRNA-LNP-based vaccines encoding both hemagglutinin (HA) and neuraminidase (NA) proteins from the human-isolated highly pathogenic avian influenza H5N1 strain, A/Texas/37/2024, in a single open reading frame. This dual-antigen expression approach elicited strong protective immune responses targeting both the HA and NA proteins and provided complete protection against lethal viral challenges in a murine model. The pre-clinical data described in this work suggest that these multi-valent, adaptable, and scalable vaccine approaches may represent practical and rapid solutions to mediate robust protection from emerging zoonotic influenza virus threats.


IMPORTANCE

Vaccines capable of protecting from infection with the H5N1 influenza viruses actively circulating in dairy cattle could be deployed to protect livestock and potentially also be used to protect human health. Here, we describe the development of protective DNA and mRNA-lipid nanoparticle vaccines targeting hemagglutinin and neuraminidase proteins from the highly pathogenic avian influenza (HPAI) H5N1 A/Texas/37/2024 virus and show that they are both protective against severe morbidity and mortality in a mouse model. Thus, the vaccines described in this work represent effective approaches to limit the current circulation of H5N1 viruses in animals and may represent practical solutions for human vaccination in the event of sustained human transmission of HPAI H5N1 viruses.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00795-25?af=R

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Low levels of #H5N1 HA and NA #antibodies in the #human population are boosted by seasonal #H1N1 #infection but not by #H3N2 infection or influenza #vaccination

Abstract

An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus. Preexisting 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 responses were detected in a cohort of 73 individuals. Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses 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 neutralizing antibody, as well as increases in NA-binding and NA-inhibiting antibodies to bovine A/H5N1 NA. While the degree of protection afforded by these A/H5N1 cross-reactive antibodies is not known, incorporating NA or enhancing current seasonal vaccine formulations to increase NA-specific antibody responses may increase antibody breadth and protection against both seasonal and pandemic influenza viruses.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.13.664638v1

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

 



By Scott Wieman - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=24620634


A wild Herring Gull in Nordland Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6621

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#Russia - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification


Di dierat-stock - Crow-1, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=33155653


A wild Carrion Crow in Khabarovsk Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6622

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The #impact of highly pathogenic avian #influenza #H5N1 virus infection on dairy #cows

Abstract

Highly pathogenic avian influenza (HPAI) H5N1 virus has been associated with severe mastitis in dairy cows, leading to decreased milk production. Here we investigated the impact of H5N1 virus infection in health and production parameters in an affected dairy herd in Ohio. Clinical disease, which lasted for about three weeks, was recorded in 20.0% (777/3876) of the adult cows. Milk losses of ~900 kg per cow were recorded in affected cows during a 60 day-post-outbreak period. Seroprevalence was 89.4% (570/637) in the herd, with 76.1% (485/637) of seropositive animals being subclinically infected. Clinically affected cows presented an increased risk of death (6 times) and of premature herd removal (3.6 times) when compared to non-clinical cows. Economic losses due to decreased milk production, mortality, and early herd removal were estimated at $950 per clinically affected cow for a total cost of ~$737,500 for the herd during the observation period. Our results demonstrate a production impact lasting at least 60 days post-clinical diagnosis and major financial consequences of HPAI H5N1 virus infection to dairy farms.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61553-z

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#Surveillance and follow up #outcomes of #myocarditis after #mRNA #COVID19 #vaccination in #Australia

Abstract

Clinical progression and medium-long term morbidity from myocarditis following mRNA COVID-19 vaccinations remains an important but undefined public health concern. We conducted prospective follow-up of individuals with either confirmed or probable myocarditis following monovalent Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccination between 21 April 2021 and 5 July 2022 in Australia. Of 256 individuals who consented to follow up, mostly males following a second dose, 60% (133/221) had ongoing symptoms at 3-6 months and 35% (81/231) at 12-18 months. Self-reported ongoing exercise restrictions, medication requirements, and hospital re-presentations were associated with ongoing symptoms, as was a lower self-reported health status and quality of life. Clinical severity remained mild, with low hospitalisation rates and no deaths in the follow-up period and health-related quality of life improved over time. These findings support ongoing use of mRNA COVID-19 vaccines in at-risk individuals to prevent disease caused by SARS-CoV-2 infection.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01206-w

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Tuesday, July 15, 2025

Emergence of #Parechovirus-A5 #CNS #infections in #children from #Kansas City, #Missouri, #USA

HIGHLIGHTS

• PeV-A5 was the predominant PeV-A genotype detected from CSF/blood in 2024 at CM-KC.

• CM-KC PeV-A5 sequences resemble PeV-A5 sequences reported in Sapporo City, Japan, in 2018.

• The highest number of PeV-A5 detections within a single year in the USA.


ABSTRACT

Background

Parechovirus-A5 (PeV-A5) blood and central nervous system (CNS) infections are rare in the United States of America (USA) and globally. We report an emergence of PeV-A5 infections among infants in Kansas City, Missouri, in 2024.

Methods

Cerebrospinal fluid (CSF) and blood samples from infants were tested for Parechovirus (PeV-A) in 2024 as a part of standard of care at Children's Mercy Kansas City (CM-KC). PeV-A testing included a two-step reverse transcriptase-polymerase chain reaction, and genotyping was conducted using Sanger sequencing. We analyzed the amino acid sequences and phylogeny of the 2024 PeV-A viruses and described the clinical characteristics of PeV-A infected infants.

Results

Among 211 CSF and 46 blood samples from 248 patients, 10 (4%) PeV-A infected patients were detected (8 CSF, 2 blood). Genotyping was successful for viruses from 9 PeV-A infected patients, with 8 identified as PeV-A5 (6 CSF, 2 blood) and 1 as PeV-A4 (CSF). PeV-A5 viral sequences from CM-KC clustered with other known PeV-A5 sequences, being most similar (>97%) to a PeV-A5 viral sequence from Sapporo City, Japan, in 2018. PeV-A5 detections from CM-KC occurred with a summer-fall seasonality. All 8 PeV-A5 infected patients had symptoms of rash with less irritability and lower maximum temperature when compared to previous PeV-A3 and PeV-A4 infected patients at CM-KC.

Conclusions

PeV-A5 emerged as the predominant PeV-A genotype detected from sterile sites (CSF, blood) in infants in Kansas City, Missouri in 2024, representing the highest number of PeV-A5 systemic illness in infants in the USA within a year.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000770?dgcid=rss_sd_all

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Co-circulation of distinct high pathogenicity avian #influenza virus #subtypes in a mass #mortality event in wild #seabirds and co-location with dead #seals

Abstract

H5Nx clade 2.3.4.4b high pathogenicity avian influenza viruses (HPAIV) have been detected repeatedly in Great Britain (GB) since autumn 2020, with H5N1 dominating detections but with low level detection of H5N5 during 2025. Globally, these viruses have caused mass mortalities in captive and wild avian and mammalian populations, including terrestrial and marine mammals. H5N1 has been the dominant subtype, and whilst incursions have overlapped temporally, occurrences have often been spatially distinct. Here, we report the detection of a mortality event in wild birds on the Norfolk coastline in the east of England, where H5N1 HPAIV was detected in five Great Black-backed Gulls (Larus marinus) and a Northern Fulmar (Fulmarus glacialis). Interestingly, at the same site, and as part of the same mortality event, a total of 17 Great Black-backed Gulls, one Herring Gull (Larus argentatus), one Atlantic Puffin (Fratercula arctica) and one Northern Fulmar tested positive for H5N5 HPAIV. Additionally, H5N5 was also detected in 17 co-located Grey Seal carcases (Halichoerus grypus). The H5N1 HPAIV from an infected bird belonged to genotype DI.2, closely related to contemporaneous detections in GB wild birds and poultry. In contrast, all H5N5 HPAIVs from birds and seals were genotype I with a 22-amino acid stalk deletion in NA and the 627K polymorphism in PB2. This represents the first recorded instance in GB of two subtypes being detected within the same avian population at the same location. It is also the first mass detection of HPAIV H5N5 in mammals within GB. Potential infection mechanisms are discussed.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.11.664278v1

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Extended #nirmatrelvir–ritonavir #treatment durations for immunocompromised #patients with #COVID19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial

Summary

Background

Nirmatrelvir–ritonavir is approved for adults with mild-to-moderate COVID-19 who are at risk of severe disease. There are little clinical data to guide the duration of therapy in patients who are immunocompromised. We aimed to compare the approved 5-day regimen of nirmatrelvir–ritonavir with 10-day and 15-day regimens.

Methods

This placebo-controlled, randomised, double-blind, phase 2 trial enrolled non-hospitalised, immunocompromised individuals aged 12 years or older with symptomatic COVID-19 from 73 sites across nine countries. Participants were randomly assigned (1:1:1) to receive 300 mg nirmatrelvir and 100 mg ritonavir orally twice per day for 5, 10, or 15 days. Randomisation was stratified according to whether participants were considered immunocompromised due to use of corticosteroids or tumour necrosis factor blockers. Investigators, participants, and caregivers were masked to the assigned study group. The primary endpoint was proportion of randomly assigned and dosed participants with sustained nasopharyngeal SARS-CoV-2 RNA concentrations below the lower limit of quantification (2·0 log10 copies per mL) from days 15 to 44. Secondary endpoints included the incidence of viral rebound after the end of treatment up to day 44. Safety, a secondary endpoint, was assessed in all randomly assigned participants who received at least one dose of nirmatrelvir–ritonavir. This trial was registered with ClinicalTrials.gov (NCT05438602) and is completed.

Findings

Among 156 participants (84 female, 72 male) randomly assigned from Aug 3, 2022 to July 17, 2023, 150 comprised the analysis population. The primary endpoint was reached in 32 (61·5%, 95% CI 48·3–74·8) of 52 participants in the 5-day treatment group, 34 (70·8%, 58·0–83·7) of 48 participants in the 10-day treatment group, and 33 (66·0%, 52·9–79·1) of 50 participants in the 15-day treatment group. Viral rebound occurred in 17·3% (95% CI 8·2–30·3) of participants in the 5-day group, 2·1% (0·1–11·1) in the 10-day group, and 2·0% (0·1–10·6) in the 15-day group. Adverse events occurred in 28 (52·8%) of 53, 34 (66·7%) of 51, and 31 (60·8%) of 51 participants across the 5-day, 10-day, and 15-day groups, respectively. Two COVID-19-related hospitalisations were reported, both in the 5-day treatment group.

Interpretation

No difference was observed between the three treatment durations in the primary endpoint. Extending nirmatrelvir–ritonavir treatment beyond 5 days resulted in a nominal improvement in the frequency of viral rebound and was generally well tolerated.

Funding

Pfizer.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00221-X/fulltext?rss=yes

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Efficacy and safety of #obeldesivir in low-risk, non-hospitalised #patients with #COVID19 (OAKTREE): a phase 3, randomised, double-blind, placebo-controlled study

Summary

Background

Obeldesivir is an oral nucleoside analogue prodrug antiviral that inhibits SARS-CoV-2 replication. We aimed to assess the efficacy, safety, and tolerability of obeldesivir for the treatment of COVID-19 in non-hospitalised individuals at low risk of progression to severe disease.

Methods

OAKTREE was a phase 3, randomised, double-blind, placebo-controlled trial in 107 centres (including research centres, primary care centres, and hospitals) in Japan and the USA. Low-risk, non-hospitalised adults and adolescents with mild-to-moderate COVID-19 were enrolled within 3 days of symptom onset. Eligible participants were randomly assigned 1:1 using permuted block randomisation (block size of four), stratified by historical completion of a primary COVID-19 vaccination series, to receive either oral obeldesivir 350 mg or matched placebo twice daily for 5 days. The primary efficacy endpoint was time to COVID-19 symptom alleviation by day 29, which was assessed in all randomly assigned participants who received one or more doses of study drug, had positive SARS-CoV-2 RT-PCR (per central laboratory testing) at baseline, and had COVID-19 symptom data (full analysis positive set). The primary safety endpoint was the incidence of adverse events and laboratory abnormalities and was assessed in all randomly assigned participants who received one or more doses of study drug. As a secondary endpoint we assessed change from baseline in nasal swab viral RNA copy number at day 5 in all randomly assigned participants who received one or more doses of study drug and had a quantifiable baseline value. This trial is registered with ClinicalTrials.gov, NCT05715528, and is complete.

Findings

Between Feb 13, 2023 and Oct 31, 2023, 1955 participants (1155 female and 800 male; 1698 White, 207 Black, 42 Asian, and eight Other) were randomly assigned and received at least one dose of either obeldesivir (n=979) or placebo (n=976). Overall, 1368 (70·0%) participants had completed a primary COVID-19 vaccination series and 1938 (99·6%) were seropositive for SARS-CoV-2 antibodies. There were 884 participants in each group in the full analysis positive set. Among those in the full analysis positive set who completed the symptom questionnaire (ie, who had COVID-19 symptom data; 879 obeldesivir, 882 placebo), median time to COVID-19 symptom alleviation was 5·9 days (95% CI 5·4–6·1) in the obeldesivir group and 6·0 days (5·8–6·3) in the placebo group (hazard ratio 1·099 [95% CI 0·997–1·211], p=0·068). The least-squares mean change from baseline in viral RNA copy number at day 5 was –2·13 log10 copies per mL (SE 0·04) and –1·95 log10 copies per mL (0·04) for the obeldesivir group (n=637) and placebo group (n=622), respectively, with a least-squares mean difference of –0·18 (95% CI –0·30 to –0·06) log10 copies per mL (p=0·0037). The safety profile was comparable between groups. 53 (5·4%) of 979 participants in the obeldesivir group and 56 (5·7%) of 976 participants in the placebo group had one or more treatment-emergent adverse events. 753 (77·5%) participants in the obeldesivir group and 757 (78·5%) participants in the placebo group had one or more graded laboratory abnormalities, most of which were grade 1 or 2.

Interpretation

Obeldesivir was generally safe and well tolerated, with greater reduction of SARS-CoV-2 viral RNA copy number versus placebo at day 5. However, obeldesivir did not significantly reduce time to symptom alleviation, possibly reflecting the challenges of assessing efficacy in this population in an era of high rates of vaccine-induced and natural immunity.

Funding

Gilead Sciences.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00238-5/fulltext?rss=yes

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Monday, July 14, 2025

Viral #tropism is a cornerstone in the spread and #spillover of avian #influenza viruses

ABSTRACT

In recent years, high pathogenicity avian influenza viruses (HPAIVs) have spread among wild, captive, and domestic birds, as well as mammals. Beyond the resulting economic and ecological losses, spillover into mammals has raised concerns about a potential pandemic. Viral tropism refers to the spectrum of host species, organs, and cells susceptible and permissive to viral infection. It is a potent driver of infection dynamics and shedding patterns, which presents important variations both between and within hosts: in poultry, HPAIV leads to systemic endothelial infection in domestic chickens, whereas neurological and selective epithelial infections are observed in domestic ducks. In mammals, infection can result in respiratory and neurological disease, but the recent outbreaks in domestic dairy cows highlighted a unique and remarkable adaptation to the mammary gland prone to viral shedding in milk. The present review explores viral tropism of HPAIV across recent spillover from birds to mammals and discusses its critical involvement in viral ecology, requiring the constant surveillance and adaptation of control measures.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.01690-25

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#Neurologic Manifestations Associated with #Parvovirus B19 #Epidemic, #Madrid, #Spain, 2024

Abstract

A reemergence of parvovirus B19 infections in Spain in early 2024 prompted a 10-year review of the virus at a tertiary center. We identified 8 case-patients with neurologic manifestations who had parvovirus B19 in cerebrospinal fluid. Early recognition and management of parvovirus B19–associated neurologic conditions will help yield favorable outcomes.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0278_article

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#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 28 May to 1 July 2025 (#WHO)


 

New human cases{2}: 

-- From 28 May to 1 July 2025, based on reporting date, the detection of influenza A(H5N1) in nine humans, influenza A(H9N2) in three humans and influenza A(H10N3) in one human were reported officially. Additionally, one human case of infection with an influenza A(H5N1) virus was detected. 

Circulation of influenza viruses with zoonotic potential in animals

-- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).{3} The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4} 

Risk assessment{5}: 

-- Sustained human to human transmission has not been reported from these events. 

-- Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not changed remains low

-- The occurrence of sustained human-to-human transmission of these viruses is currently considered unlikely

-- Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.  

IHR compliance

-- All human infections caused by a new influenza subtype are required to be reported under the International Health Regulations (IHR, 2005).{6} 

-- This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin (HA) gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. 

-- Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.  


Avian influenza viruses in humans 

Current situation:  

Since the last risk assessment of 27 May 2025, single laboratory-confirmed human cases of A(H5N1) infection were detected in Bangladesh and India. Eight confirmed human cases of A(H5N1) infection were reported to WHO from Cambodia

-- A(H5N1), Bangladesh 

On 31 May 2025, Bangladesh notified WHO of one confirmed human case of avian influenza A(H5) in a child in Chittagong division detected through hospital-based surveillance. The patient was admitted to hospital on 21 May with diarrhea, fever and mild respiratory symptoms and a respiratory sample was collected on admission. On 28 May, the IEDCR confirmed infection with avian influenza A(H5) through RT-PCR. The N-type was later confirmed as N1. The patient has recovered, and exposure to backyard poultry was reported prior to symptom onset. No further cases were detected among the contacts of the case. This is the 11th human infection with influenza A(H5N1) notified to WHO from Bangladesh since the first case was reported in the Dhaka division in 2008 and the third confirmed case in 2025. 

-- A(H5N1), Cambodia 

Between 29 May and 1 July 2025, Cambodia notified WHO of eight laboratory-confirmed cases of A(H5N1) virus infection.  

(...)

All cases above had exposure to sick or dead backyard poultry. The most recent case was from a different village than the other three cases from Siem Reap. The 46-year-old female and the 16-yearold male cases are members of the same family and are neighbors of the first case detected in Siem Reap; they were sampled as part of active case finding during the response to the first case because they also handled sick and dead poultry from their own backyard. 

Rapid response teams from the public health and animal health sectors have been deployed to investigate and respond to the outbreak.  

Eleven human infections with A(H5N1) viruses have been confirmed in Cambodia in 2025 and six of these have been fatal

All these cases in 2025 had exposure to domestic birds or their environments. In some cases, the domestic birds were reported to be sick or dead. 

Influenza A(H5N1) viruses continue to be detected in domestic birds in Cambodia in 2025, including in areas where human cases have been detected.{7} 

Where the information is available, the genetic sequence data from the viruses from the human cases closely matches that from recent local animal viruses and are identified as clade 2.3.2.1e viruses. From the information available thus far on these recent human cases, there is no indication of human-to-human transmission of the A(H5N1) viruses.  

-- A(H5N1), India  

A human infection with an H5 clade 2.3.2.1a A(H5N1) virus was detected in a sample collected from a man in Khulna state in May 2025, who subsequently died. Genetic sequence data are available in GISAID (EPI_ISL_19893416; submission date 4 June 2025; ICMR-National Institute of Virology; Influenza). 

According to reports received by WOAH, various influenza A(H5) subtypes continue to be detected in wild and domestic birds in Africa, the Americas, Asia and Europe. 

Infections in non-human mammals are also reported, including in marine and land mammals.{8} A list of bird and mammalian species affected by HPAI A(H5) viruses is maintained by FAO.{9}    


Risk Assessment for avian influenza A(H5N1) viruses:  

1. What is the current global public health risk of additional human cases of infection with avian influenza A(H5N1) viruses?  

-- Most human cases so far have been infections in people exposed to A(H5) viruses, for example, through contact with infected poultry or contaminated environments, including live poultry markets, and occasionally infected mammals and contaminated environments. While the viruses continue to be detected in animals and related environments humans are exposed to, further human cases associated with such exposures are expected but unusual. The impact for public health if additional cases are detected is minimal. The current overall global public health risk of additional human cases is low

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H5N1) viruses related to the events above?  

No sustained human-to-human transmission has been identified associated with the recent reported human infections with avian influenza A(H5N1) viruses. There has been no reported human-tohuman transmission of A(H5N1) viruses since 2007, although there may be gaps in investigations. In 2007 and the years prior, small clusters of A(H5) virus infections in humans were reported, including some involving health care workers, where limited human-to-human transmission could not be excluded; however, sustained human-to-human transmission was not reported.  Current evidence suggests that influenza A(H5N1) viruses related to these events did not acquire the ability to efficiently transmit between people, therefore the likelihood of sustained human-tohuman transmission is thus currently considered unlikely.  

3. What is the likelihood of international spread of avian influenza A(H5N1) viruses by travellers?  

Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further community-level spread is considered unlikely as current evidence suggests these viruses have not acquired the ability to transmit easily among humans.  


-- A(H9N2), China

Since the last risk assessment of 27 May 2025, three human cases of infection with A(H9N2) influenza viruses were notified to WHO from China on 9 June 2025. The cases were detected in Henan, Hunan and Sichuan provinces. Two infections were detected in adults who were also hospitalized. The cases had symptom onset in May 2025 and have recovered. All cases had a known history of exposure to poultry prior to the onset of symptoms. No further cases were detected among contacts of these cases and there was no epidemiological link between the cases.   

Risk Assessment for avian influenza A(H9N2):   

1. What is the global public health risk of additional human cases of infection with avian influenza A(H9N2) viruses?   

Most human cases follow exposure to the A(H9N2) virus through contact with infected poultry or contaminated environments. Most human infections of A(H9N2) to date have resulted in mild clinical illness. Since the virus is endemic in poultry in multiple countries in Africa and Asia{11}, further human cases associated with exposure to infected poultry are expected but remain unusual. The impact to public health if additional cases are detected is minimal. The overall global public health risk of additional human cases is low.  

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H9N2) viruses related to this event?   

At the present time, no sustained human-to-human transmission has been identified associated with the recent reported human infections with A(H9N2) viruses. Current evidence suggests that influenza A(H9N2) viruses from these cases did not acquire the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely.   

3. What is the likelihood of international spread of avian influenza A(H9N2) virus by travellers?   

Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. If this were to occur, further community level spread is considered unlikely as current evidence suggests the A(H9N2) virus subtype has not acquired the ability to transmit easily among humans.   


-- A(H10N3), China  

On 9 June 2025, China notified the WHO of one confirmed case of human infection with avian influenza A(H10N3) virus in an adult from Shaanxi Province, with a history of asthma. Symptom onset occurred on 21 April, and the patient was admitted to hospital with pneumonia on 25 April. At the time of reporting, that patient was under treatment and improving.    According to the epidemiological investigation, a history of exposure to backyard poultry in Inner Mongolia was reported. The patient is a farmer and raises chickens and sheep. Environmental samples did not test positive for influenza A(H10) viruses. All close contacts tested negative for influenza A and remained asymptomatic during the monitoring period.    Since 2021, China has notified WHO of a total of six confirmed human cases of avian influenza A(H10N3) virus infection. 

Risk Assessment for avian influenza A(H10N3):   

1. What is the global public health risk of additional human cases of infection with avian influenza A(H10N3) viruses?   

Human infections with avian influenza A(H10) viruses have been detected and reported previously.   The circulation and epidemiology of these viruses in birds have been previously reported.{12} Avian influenza A(H10N3) viruses with different genetic characteristics have been detected previously in wild birds since the 1970s and more recently spilled over to poultry in some countries. As long as the virus continues to circulate in birds, further human cases can be expected but remain unusual. The impact to public health if additional sporadic cases are detected is minimal. The overall global public health risk of additional sporadic human cases is low.    

2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H10N3) viruses related to this event?   

No sustained human-to-human transmission has been identified associated with the event described above or past events with human cases of influenza A(H10N3) viruses. Current epidemiologic and virologic evidence suggests that influenza A(H10N3) viruses related to this event did not acquire the ability of sustained transmission among humans, therefore sustained human-tohuman transmission is thus currently considered unlikely.    

3. What is the likelihood of international spread of avian influenza A(H10N3) virus by travellers?   

Should infected individuals from affected areas travel internationally, their infection may be   detected in another country during travel or after arrival. If this were to occur, further community   level spread is considered unlikely based on current limited evidence.   


Overall risk management recommendations

Surveillance and investigations 

Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global strategic surveillance in animals and humans to detect virologic, epidemiologic and clinical changes associated with circulating influenza viruses that may affect human (or animal) health. Continued vigilance is needed within affected and neighbouring areas to detect infections in animals and humans. Close collaboration with the animal health and environment sectors is essential to understand the extent of the risk of human exposure and to prevent and control the spread of animal influenza. WHO has published guidance on surveillance for human infections with avian influenza A(H5) viruses. 

As the extent of influenza virus circulation in animals is not clear, epidemiologic and virologic surveillance and the follow-up of suspected human cases should continue systematically. Guidance on investigation of non-seasonal influenza and other emerging acute respiratory diseases has been published on the WHO website. 

Countries should increase avian influenza surveillance in domestic and wild birds, enhance surveillance for early detection in cattle populations in countries where HPAI is known to be circulating, include HPAI as a differential diagnosis in non-avian species, including cattle and other livestock populations, with high risk of exposure to HPAI viruses; monitor and investigate cases in non-avian species, including livestock, report cases of HPAI in all animal species, including unusual hosts, to WOAH and other international organizations, share genetic sequences of avian influenza viruses in publicly available databases, implement preventive and early response measures to break the HPAI transmission cycle among animals through movement restrictions of infected livestock holdings and strict biosecurity measures in all holdings, employ good production and hygiene practices when handing animal products, and protect persons in contact with suspected/infected animals.{10}  

When there has been human exposure to a known outbreak of an influenza A virus in domestic poultry, wild birds or other animals – or when there has been an identified human case of infection with such a virus – enhanced surveillance in potentially exposed human populations becomes necessary. Enhanced surveillance should consider the health care seeking behaviour of the population, and could include a range of active and passive health care and/or community-based approaches, including: enhanced surveillance in local influenza-like illness (ILI)/SARI systems, active screening in hospitals and of groups that may be at higher occupational risk of exposure, and inclusion of other sources such as traditional healers, private practitioners and private diagnostic laboratories. 

Vigilance for the emergence of novel influenza viruses of pandemic potential should be maintained at all times including during a non-influenza emergency. In the context of the cocirculation of SARS-CoV-2 and influenza viruses, WHO has updated and published practical guidance for integrated surveillance. 


Notifying WHO 

All human infections caused by a new subtype of influenza virus are notifiable under the International Health Regulations (IHR, 2005).{11} State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed{12} case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic{13}. Evidence of illness is not required for this report. 

WHO published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005): https://www.who.int/teams/global-influenzaprogramme/avian-influenza/case-definitions


Virus sharing and risk assessment 

It is critical that these influenza viruses from animals or from people are fully characterized in appropriate animal or human health influenza reference laboratories. Under WHO’s Pandemic Influenza Preparedness (PIP) Framework, Member States are expected to share influenza viruses with pandemic potential on a timely basis{14} with a WHO Collaborating Centre for influenza of GISRS. The viruses are used by the public health laboratories to assess the risk of pandemic influenza and to develop candidate vaccine viruses.  

The Tool for Influenza Pandemic Risk Assessment (TIPRA) provides an in-depth assessment of risk associated with some zoonotic influenza viruses – notably the likelihood of the virus gaining human-to-human transmissibility, and the impact should the virus gain such transmissibility. TIPRA maps relative risk amongst viruses assessed using multiple elements. The results of TIPRA complement those of the risk assessment provided here, and those of prior TIPRA analyses will be published at http://www.who.int/teams/global-influenza-programme/avian-influenza/toolfor-influenza-pandemic-risk-assessment-(tipra).  


Risk reduction 

Given the observed extent and frequency of avian influenza in poultry, wild birds and some wild and domestic mammals, the public should avoid contact with animals that are sick or dead from unknown causes, including wild animals, and should report dead birds and mammals or request their removal by contacting local wildlife or veterinary authorities.  

Eggs, poultry meat and other poultry food products should be properly cooked and properly handled during food preparation. Due to the potential health risks to consumers, raw milk should be avoided. WHO advises consuming pasteurized milk. If pasteurized milk isn’t available, heating raw milk until it boils makes it safer for consumption. 

WHO has published practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses. 


Trade and travellers 

WHO advises that travellers to countries with known outbreaks of animal influenza should avoid farms, contact with animals in live animal markets, entering areas where animals may be slaughtered, or contact with any surfaces that appear to be contaminated with animal excreta. Travelers should also wash their hands often with soap and water. All individuals should follow good food safety and hygiene practices.  

WHO does not advise special traveller screening at points of entry or restrictions with regards to the current situation of influenza viruses at the human-animal interface. For recommendations on safe trade in animals and related products from countries affected by these influenza viruses, refer to WOAH guidance.  


Links:  

-- WHO Human-Animal Interface web page https://www.who.int/teams/global-influenza-programme/avian-influenza 

-- WHO Influenza (Avian and other zoonotic) fact sheet https://www.who.int/news-room/fact-sheets/detail/influenza-(avian-and-other-zoonotic) 

-- WHO Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases https://www.who.int/publications/i/item/WHO-WHE-IHM-GIP-2018.2 

-- WHO Public health resource pack for countries experiencing outbreaks of influenza in animals:  https://www.who.int/publications/i/item/9789240076884 

-- Cumulative Number of Confirmed Human Cases of Avian Influenza A(H5N1) Reported to WHO  https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-a-h5n1-virus 

-- Avian Influenza A(H7N9) Information https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-influenza-a-(h7n9)virus 

-- World Organisation of Animal Health (WOAH) web page: Avian Influenza  https://www.woah.org/en/home/ 

-- Food and Agriculture Organization of the United Nations (FAO) webpage: Avian Influenza https://www.fao.org/animal-health/avian-flu-qa/en/ 

-- OFFLU http://www.offlu.org/ 

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{1} This summary and assessment covers information confirmed during this period and may include information received outside of this period. 

{2} For epidemiological and virological features of human infections with animal influenza viruses not reported in this assessment, see the reports on human cases of influenza at the human-animal interface published in the Weekly Epidemiological Record here.  

{3} World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2

{4} Food and Agriculture Organization of the United Nations (FAO). Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential

{5} World Health Organization (2012). Rapid risk assessment of acute public health events. World Health Organization. Available at: https://iris.who.int/handle/10665/70810

{6} World Health Organization. Case definitions for the 4 diseases requiring notification to WHO in all circumstances under the International Health Regulations (2005). Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005).   

{7} https://wahis.woah.org/#/in-event/5754/dashboard 

{8} World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2

{9} Food and Agriculture Organization of the United Nations. Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential/bird-species-affected-by-h5nx-hpai/en

{10} World Organisation for Animal Health. Statement on High Pathogenicity Avian Influenza in Cattle, 6 December 2024. Available at: https://www.woah.org/en/high-pathogenicity-avian-influenza-hpai-in-cattle/

{11} World Health Organization. Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005).    

{12} World Health Organization. Manual for the laboratory diagnosis and virological surveillance of influenza (2011). Available at: https://apps.who.int/iris/handle/10665/44518 

{13} World Health Organization. Pandemic influenza preparedness framework for the sharing of influenza viruses and access to vaccines and other benefits, 2nd edition. Available at: https://iris.who.int/handle/10665/341850 

{14} World Health Organization. Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework (2017). Available at: https://apps.who.int/iris/handle/10665/25940 

Source: World Health Organization, https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--1-july-2025

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Sunday, July 13, 2025

#Risk #Assessment #Report using #TIPRA - 2nd edition For Avian #influenza clade 2.3.4.4b #H5N1 #B313 viruses - Executive Summary (#WHO)



{Excerpt}

1. Background 

A risk assessment exercise using the Tool for Influenza Pandemic Risk Assessment (TIPRA) was conducted for Clade 2.3.4.4b A(H5N1) genotype B3.13 virus in Aug – Oct 2024.  

From late 2023, unexplained illnesses were reported in dairy cattle across multiple states in the United States

Following those events, detection of avian influenza A(H5N1) in dairy cattle from Texas was confirmed on 25 March 2024. 

As of 9 December 2024, the virus has been detected in 720 dairy cattle herds across 15 states, according to the United States Department of Agriculture (USDA), with a total of 47 human infections from poultry and dairy cattle sources, excluding 11 human cases from Washington state, that might belong to genotype D1.1, also reported. 

Wild and domestic animals (e.g., cats, raccoons) near infected herds have been affected as well. 

The outbreak remains uncontrolled

Due to the unprecedented spread of the virus among dairy cattle and associated human cases, a pandemic risk assessment was warranted to evaluate its potential impact and identify research gaps. 


2. Objectives 

Characterize the pandemic risk from Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses. 

Identify knowledge gaps for Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses. 

Recognize strengths, limitations, and room for improvement of the risk assessment protocol of TIPRA for further facilitation and standardization. 

Engage international stakeholders in TIPRA to help facilitate information sharing for current and future assessments. 


3. Risk Question 

What is the overall public health risk of Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses, as compared to other viruses that were subject to previous TIPRA exercises? 

For this risk question, two components were assessed: 

-- the likelihood of the viruses acquiring the capacity for sustained human-to-human transmission and 

-- the public health impact if human-to-human transmission were to occur.  


4. Risk Assessment 

Method 

Tool Applied 

The Tool for Influenza Pandemic Risk Assessment (TIPRA) was used to assess the above risk question. 

As per Step 1 in TIPRA, epidemiological and virological criteria triggered a risk assessment of Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses. 

The triggering was based on the following the internal epidemiological and experimental information provided from multiple stakeholders provided and literature review: 

• The first detection of avian A(H5N1) viruses from dairy cattle, 

• The sporadic but ongoing detection of human cases of avian A(H5N1) infection, 

• The multiple outbreaks and spread of avian influenza A(H5N1) viruses among dairy cattle,  

• Specific genotypes  of avian influenza A(H5N1) viruses isolated among dairy cattle, human, birds, and wild animals, 

• Molecular signatures associated with better replication in mammals. 

The risk was characterized using the statistical model described in TIPRA. 

Technical experts (TEs) scored risk elements based on evidence (a virus profile1) available about the virus at the time of assessment, and discussions based on the scores were used to characterize the risk and develop recommendations. 

Ten risk elements are described in the TIPRA guidance. The ten risk elements and their relevant weights per component (likelihood and impact) were then applied and risk scores generated.  


Summary of relative risk evaluation result of Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses 

-- Date of Assessment: Risk assessment teleconference date on 22 August and 10 October 2024 

-- Final risk scores: Likelihood: 5.62, Impact: 4.25 

-- Countries that have reported human infections: United States of America

Risk evaluation

- Clade 2.3.4.4b A(H5N1) genotype B3.13 viruses have moderate likelihood of developing sustained human-to-human transmission capacity with low to moderate impact on the human population if the event occurs.  

- Confidence level: Moderate confidence for likelihood, moderate confidence for impact. Risk assessed was underpinned by the information available in October 2024 and the knowledge provided by TEs.  

(...)

Source: World Health Organization, https://cdn.who.int/media/docs/default-source/influenza/tipra/tipra-risk-assessment-reports/outcome-summaries/15.-oct-2024_h5n1-b3.13__summary-report.pdf?sfvrsn=65ed5a2a_3

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The Seven Deadly Sins and the Four Last Things, Hieronymus Bosch (1485)

 


Public Domain.

Source: WikiArt, https://www.wikiart.org/en/hieronymus-bosch/the-seven-deadly-sins-and-the-four-last-things-1485

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#Thermal #tolerance and #inactivation of #Ebola virus

{Summary}

HIGHLIGHTS

• The investigation demonstrated a high level of tolerance of EBOV to thermal disinfection.

• A water-bath is recommended and the tubes should be fully submerged during the process.

• The established inactivation guidelines should be followed very strictly.


Dear Editor,

Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever, with case fatality rates ranging from 25% to 90% (Mahanty and Bray, 2004). Six species of the virus (Orthoebolavirus zairense, sudanense, bundibugyoense, taiense, restonense, and bombaliense) have so far been identified (Biedenkopf et al., 2023). Among these, Orthoebolavirus zairense, commonly known as Ebola virus (EBOV), stands out as the most virulent. Given its high contagiousness and lethality, EBOV must be manipulated under biosafety level 4 (BSL-4) conditions, as stipulated by the National Health Commission of the People's Republic of China's list of human pathogenic microorganisms. Prior to being removed from a BSL-4 laboratory, it is imperative that infectious EBOV undergoes complete inactivation. Here we systematically evaluate viral thermostability under BSL-4 containment conditions, demonstrating EBOV’s marked thermotolerance.

(...)

Source: Virologica Sinica, https://www.sciencedirect.com/science/article/pii/S1995820X25000975

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