Friday, August 1, 2025

A #Genome #Sequence Variant #Monitoring Program for Seasonal #Influenza #H3N2 & #RSV using #Wastewater-Based #Surveillance in #Ontario, Canada

Abstract

Seasonal respiratory viruses, such as the Influenza A virus and the respiratory syncytial virus, are responsible for over a billion infections worldwide each year resulting in a substantial burden on health care systems. Surveillance of these viruses, including their prevalence in communities and their evolution, are essential for informing public health decisions and recommending vaccine formulations and schedules. Typically, these viruses are monitored using clinical samples from patients seeking medical attention. Recently, wastewater-based surveillance (WBS) has been leveraged to understand transmission dynamics and genome evolution of SARS-CoV-2 and seasonal respiratory viruses. To further the utility of WBS we developed and implemented novel tiled-amplicon sequencing assays to identify and track Influenza A virus H3N2 and respiratory syncytial virus A circulating in Southern Ontario, Canada. We also developed virus specific deconvolution tools to estimate the abundance of mixed lineages in wastewater. These assays were able to accurately determine which lineages were circulating in wastewater with high sensitivity and specificity. If implemented in regular surveillance programs, they could be used to inform real-time public health decisions and determine potential disease surge with impact on emergency room visits and hospitalization, as well as track which emerging strains will become predominant in the future and determine which strains should be the focus of seasonal vaccines.


Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Integrated Network for the Surveillance of Pathogens (INSPIRE), CBRF2-2023-00008

Ministry of the Environment, Conservation and Parks, https://ror.org/01q2d8e83, 2021-02-1-1564736554

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.29.667219v1

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Differential modulation of #Interferon and Cell Death Responses defines #Human vs Avian #Influenza A Virus Strain-Specific Virulence and guides Combination #Therapy.

Abstract

Influenza A virus (IAV) poses a significant global health risk, with highly pathogenic strains like H5N1 (CFR ~52%) causing severe disease compared to less lethal but more transmissible strains like H1N1 (CFR 0.01-0.03%). Although IAV primarily infects lung epithelial cells, causing cell death and tissue damage, the molecular basis of strain-specific pathogenesis remains poorly understood. Here we show that in cell culture, H5N1 induced more rapid and extensive cell death than H1N1. Since Interferon (IFN) signaling is key to innate immunity, we examined its role in virus-induced cell death using STAT1-knockout A549 cells and JAK/STAT pathway inhibitors like Baricitinib. Both approaches reduced cell death across various IAV strains, including H1N1, H5N1, H7N9, and H3N2. However, inhibition increased viral titers, raising concerns about its clinical use in isolation. To overcome this, we tested a combination of Oseltamivir (antiviral) and Baricitinib (anti-inflammatory). Post-infection treatment in a murine model reduced lung inflammation and improved survival. Given that both drugs are FDA-approved, this approach has strong translational potential for clinical IAV treatment.


Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Wellcome Trust/DBT India Alliance, IA/I/18/1/503613

Indian Council of Medical Research, IIRPIG-2023-0000978

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.31.667854v1

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Thursday, July 31, 2025

Detection of #Hemagglutinin #H5 #Influenza A Virus #RNA and Model of Potential Inputs in an Urban #California #Sewershed

Abstract

In 2024, highly pathogenic avian influenza A H5N1 caused outbreaks in wild birds, poultry, cows, and other mammals in the United States with 61 human cases also reported by the CDC. Detection of influenza A H5 RNA in wastewater has been previously reported in sewersheds in Texas and North Carolina with nearby impacted dairy herds following the emergence of H5N1 in dairy cows. Here, we conduct retrospective testing of total influenza A and H5 hemagglutinin genes in wastewater as well as present and apply new assays for detection of H1 and H3 genes across a respiratory virus season in an urban California sewershed from September 2023 to May 2024. Total influenza A, H1, and H3 were regularly detected, while H5 was first detected in March. We developed a model that uses Monte Carlo simulations and previously published parameters to estimate the numbers of infected people, poultry, wild birds, or liters of H5-contaminated milk required to result in measured H5 concentrations in wastewater. Our findings demonstrate that in this California sewershed, contaminated milk or infected poultry were the most likely sources of H5 to wastewater. We created a publicly available tool to apply the H5 input model in other sewersheds to estimate the required inputs.

This publication is licensed under CC-BY 4.0. © 2025 The Authors. Published by American Chemical Society

Source: Environmental Science & Technology, https://pubs.acs.org/doi/10.1021/acs.est.4c14792

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#Genetic characterization of the #marmot gut #virome in high-altitude #Qinghai Province and identification of novel #viruses with zoonotic potential

ABSTRACT

The high-altitude ecosystems of Qinghai Province, China, harbor unique viral communities shaped by extreme environmental conditions and host adaptations. This study presents a comprehensive genetic characterization of the marmot gut virome, revealing novel viral strains with zoonotic potential. Using viral metagenomics, we analyzed intestinal contents from 70 marmots collected from Chengduo and Maqin counties. Sequencing on the Illumina NovaSeq 6000 platform identified 19 viral genomes belonging to four major families: Adenoviridae, Astroviridae, Parvoviridae, and Picornaviridae, along with four novel circular Rep-encoding single-stranded DNA (CRESS DNA) viruses. Phylogenetic analyses demonstrated close relationships between marmot-derived strains and viruses from humans, bats, and other mammals, highlighting potential cross-species transmission risks. Notably, bat-associated adenoviruses showed closer phylogenetic proximity to human strains, while novel parvoviruses formed a distinct clade within the Dependoparvovirus genus. The discovery of a novel astrovirus with low sequence similarity to known genera underscores the need for taxonomic reclassification. Additionally, a novel picornavirus related to Sapelovirus and four divergent CRESS DNA viruses were identified, expanding our understanding of viral diversity in high-altitude rodents. These findings emphasize the role of marmots as viral reservoirs and highlight the importance of high-altitude ecosystems as hotspots for zoonotic pathogen emergence. This study provides critical insights into viral evolution, host adaptation, and zoonotic risks, advocating for integrated surveillance strategies to mitigate future spillover events.


IMPORTANCE

Viruses are the most abundant and diverse biological entities on Earth, yet their presence in wildlife from extreme environments remains poorly understood. High-altitude ecosystems, shaped by harsh conditions like intense UV radiation and low oxygen levels, create unique settings for virus evolution. This study is the first to comprehensively profile the gut virome of marmots in Qinghai Province, uncovering novel viral strains and highlighting how extreme environments drive viral diversity. Marmots, as key species in these regions, can act as bridges for virus transmission among wildlife, livestock, and humans, posing zoonotic risks. Understanding these viral communities is essential for predicting and preventing future outbreaks. Our findings emphasize the urgent need for integrated, One Health-based surveillance strategies to safeguard both public health and biodiversity in fragile high-altitude ecosystems.

Source: mSphere, https://journals.asm.org/doi/full/10.1128/msphere.00297-25?af=R

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Highly pathogenic avian #influenza: #pandemic #preparedness for a #scenario of high #lethality with no #vaccines

Abstract

Highly Pathogenic Avian Influenza (HPAI) viruses, particularly H5N1 and H7N9, have long been considered potential pandemic threats, despite the absence of sustained human-to-human transmission. However, recent outbreaks in previously unaffected regions, such as Antarctica, suggest we may be shifting from theoretical risk to a more imminent threat. These viruses are no longer limited to avian populations. Their increasing appearance in mammals, including dairy cattle and domestic animals, raises the likelihood of viral reassortment and mutations that could trigger a human pandemic. If such a scenario unfolds, the world may face a crisis marked by high transmissibility and lethality, without effective vaccines readily available. Unlike the COVID-19 pandemic, when vaccines were rapidly developed despite inequities in access, the current influenza vaccine production model, largely reliant on slow, egg-based technologies, is insufficient for a fast-moving outbreak. While newer platforms show promise, they remain in early stages and cannot yet meet global demand, which alerts to the urgent need for accelerating vaccine and drug development, especially universal vaccines, next-generation vaccine platforms designed to provide broad, long-lasting protection against a wide spectrum of HPAI virus subtypes and strains. Here we propose a paradigmatic shift toward a more integrated, digitalized One Health surveillance system that links human, animal, and environmental data, especially in high-risk spillover regions. We underscore that Artificial Intelligence can revolutionize pandemic preparedness strategies, from improving early detection to speeding up vaccine and drug development and access to medical care, but should not be considered a stand-alone solution.

Source: Frontiers in Public Health, https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2025.1613869/full

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#Mpox - Multi-country external #situation #report no. 56 published 31 July 2025 (#WHO, edited)

 


{Excerpt}

Highlights

-- All clades of monkeypox virus (MPXV) continue to circulate in several countries. 

- When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, they continue to pose a risk of sustained community transmission.  

-- Since the last edition of this report, one new country, the Gambia, has reported an mpox case for the first time. 

- Genomic sequencing analysis has identified clade IIb MPXV. 

-- Furthermore, Mozambique, has reported cases of mpox due to clade Ib MPXV for the first time.  

-- Twenty-one countries in Africa have reported ongoing mpox transmission in the past six weeks. 

- Clade IIb MPXV continues to be reported in West Africa, while Central African countries report both clade Ia and clade Ib MPXV, and East African countries report clade Ib MPXV. 

-- The recent overall downward trend of confirmed cases across the continent is driven by the decline in cases in Sierra Leone and the Democratic Republic of the Congo.  

-- Uganda continues to experience community transmission of clade Ib MPXV, reporting the third-highest number of laboratory-confirmed cases in the continent. 

- Cases continue to be reported primarily among young adults of both sexes and 48% of deaths were among people living with HIV

- The slight increase in weekly cases that had been reported in the previous edition of this report appears to have been shortlived, with a downward trend reported in the most recent weeks. 

-- Australia, China and the United Kingdom have reported additional cases of mpox due to clade Ib MPXV since the last situation report. 

- These cases have been linked to travel, and community transmission of clade Ib MPXV continues to be reported only in countries in central and Eastern Africa. 

(...)

Source: World Health Organization, https://www.who.int/publications/m/item/multi-country-outbreak-of-mpox--external-situation-report--56---31-july-2025

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#Italy, Integrated #WNV & #USUV #Surveillance - Bulletin no. 3, July 31 2025 (IZS Teramo): 57 new human cases reported


{Excerpts}

During the epidemiological week comprised between 24 and 30 July 2025, there were fifty-seven new confirmed cases of human infection with West Nile Virus.

-- Since the start of the epidemic season, eighty-nine cases have been reported (there were thirty-two cases in the last week report), of which:

-- forty were WNND (West Nile Neuroinvasive Disease):

- 2 cases in Piedmont, 1 Lombardy, 3 Veneto, 1 Emilia-Romagna, twenty-three Latium, ten Campania);

-- two cases of asymptomatic infection were detected among blood donors (one in Veneto and one in Campania);

-- forty-six cases of West Nile Fever have been confirmed: 

- one in Lombardy, five in Veneto, thirty-five in Latium, four in Campania, one in Sardinia;

-- one asymptomatic case is from Campania;

-- Among confirmed cases, eight fatalities have been recorded: one in Piedmont, two in Latium and five in Campania. The case-fatality rate among WNND so far is at 20% (during epidemic seasons 2018 it was 20% and in 2024, 14%). 

-- The first case of the 2025 season was reported in Piedmont (a sporadic case in Novara Province). The second case was notified on July 3 in Modena Town. 

-- In the current epidemiological week, no confirmed human cases of infection with Usutu virus have been reported.

(...)

Source: National Veterinary Institute of Teramo, https://westnile.izs.it/j6_wnd/home

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A Phylogeny-Informed Mathematical #Modeling of #H5N1 #Transmission Dynamics and Effectiveness of #Control Measures

Abstract

The highly pathogenic avian influenza (HPAI) subtype H5N1 is a severe viral disease which continues to pose a significant threat to public health and a rigorous understanding of its transmission dynamics across its major pathways is essential for developing effective control strategies. Phylogenetic analysis suggests that H5N1 spillover occurs primarily between wild and domestic birds. However, increasing contact between these species and humans increases the risk of zoonotic transmission. In this work, we develop a mathematical model to examine the transmission dynamics of H5N1 and evaluate the effectiveness of proposed control measures. The model employs a compartmental framework that includes human, domestic, and wild bird populations. We then use this model to estimate the basic reproduction number for each population group and perform a sensitivity analysis to assess the contribution of the parameters to the spread of the disease. Numerical simulations are also conducted to evaluate the impact of inter-species interactions on H5N1 infection in humans and to determine the effectiveness of different control measures. The results suggest that a vaccination strategy with high vaccine efficacy, combined with a vaccination rate above 50%, significantly reduces transmission. In addition, decreasing cross-species interactions leads to a substantial reduction in disease transmission within the human population. Moreover, an optimal control analysis indicates that a combined approach involving environmental sanitation, vaccination, and targeted culling of confirmed infected poultry is an effective strategy to control the outbreak, reducing the likelihood of spillover to humans.


Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This work has been funded in part from the National Institute of Allergy and Infectious Diseases, a component of the NIH, Department of Health and Human Services, under contract no. 75N93021C00018 (NIAID Centers of Excellence for Influenza Research and Response, CEIRR) and Centers for Disease Control and Prevention, Department of Health and Human Services, under contract NU50CK000626.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.29.25331913v1

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Wednesday, July 30, 2025

#Influenza-Associated Acute Necrotizing #Encephalopathy in #US #Children

Key Points

-- Question: What were the clinical characteristics, management approaches, and outcomes among children with influenza-associated acute necrotizing encephalopathy (ANE) in the US during the 2023-2024 and 2024-2025 influenza seasons?

-- Findings:  In this multicenter case series of 41 children from 23 US hospitals, influenza-associated ANE carried a 27% mortality rate despite multimodal therapy. Most patients (76%) had no significant medical history, despite 15 of 32 tested (47%) having genetic risk alleles potentially related to risk of ANE identified during diagnostic evaluation. The H1 2009 influenza A strain predominated (34% of cases), and only 16% had received seasonal influenza vaccination. Among survivors, 63% had moderate to severe disability at 90-day follow-up.

-- Meaning: Influenza-associated ANE represents a rare but devastating neurologic complication primarily affecting previously healthy children. The high morbidity and mortality emphasize the need for prevention, early recognition, intensive treatment, and standardized management protocols.


Abstract

Importance

Acute necrotizing encephalopathy (ANE) is a rare, but severe, neurologic condition for which epidemiologic and management data remain limited. During the 2024-2025 US influenza season, clinicians at large pediatric centers anecdotally reported an increased number of children with influenza-associated ANE, prompting this national investigation.

Objective

To understand the clinical presentation, interventions, and outcomes among US children diagnosed with influenza-associated ANE.

Design, Setting, and Participants

This study was a multicenter case series of children diagnosed with ANE with longitudinal follow-up. A call for cases was issued via academic societies, public health agencies, and by directly contacting pediatric specialists at 76 US academic centers, requesting cases between October 1, 2023, and May 30, 2025. Inclusion criteria required acute encephalopathy with radiologic evidence of acute thalamic injury and laboratory confirmation of influenza infection in individuals aged 21 years or younger.

Exposure

Influenza-associated ANE.

Main Outcomes and Measures

Presenting symptoms, vaccination history, laboratory and genetic findings, interventions, and clinical outcomes, including modified Rankin Scale score (0: no symptoms; 1-2: mild disability; 3-5: moderate to severe disability; 6: death), length of stay, and functional outcomes.

Results  

Of 58 submitted cases, 41 cases (23 females; median age, 5 years [IQR, 2-8]) from 23 US hospitals met inclusion criteria. Thirty-one cases (76%) had no significant medical history; 5 (12%) were medically complex. Clinical presentation included fever in 38 patients (93%), encephalopathy in 41 (100%), and seizures in 28 (68%). Thirty-nine patients (95%) had influenza A (14 with A/H1pdm/2009, 7 with A/H3N2, and 18 with no subtype) and 2 had influenza B. Laboratory deviations included elevated liver enzymes (78%), thrombocytopenia (63%), and elevated cerebrospinal fluid protein (63%). Among 32 patients (78%) with genetic testing, 15 (47%) had genetic risk alleles potentially related to risk of ANE including 11 (34%) with RANBP2 variants. Among 38 patients with available vaccination history, only 6 (16%) had received age-appropriate seasonal influenza vaccination. Most patients received multiple immunomodulatory treatments, including methylprednisolone (95%), intravenous immunoglobulin (66%), tocilizumab (51%), plasmapheresis (32%), anakinra (5%), and intrathecal methylprednisolone (5%). Median intensive care unit and hospital lengths of stay were 11 days (IQR, 4-19) and 22 days (IQR, 7-36), respectively. Eleven patients (27%) died a median of 3 days (IQR, 2-4) from symptom onset, primarily from cerebral herniation (91%). Among the 27 survivors with 90-day follow-up, 63% had at least moderate disability (modified Rankin Scale score ≥3).

Conclusions and Relevance

In this case series of children with influenza-associated ANE from the 2 most recent influenza seasons in the US, the condition was associated with high morbidity and mortality in this cohort of predominantly young and previously healthy children. The findings emphasize the need for prevention, early recognition, intensive treatment, and standardized management protocols.

Source: JAMA, https://jamanetwork.com/journals/jama/fullarticle/2836871?guestAccessKey=c2292d76-607e-48ca-999a-ae3cea795c8b&utm_medium=email&utm_source=postup_jn&utm_campaign=article_alert-jama&utm_content=olf-tfl_&utm_term=073025

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


By gary noon - Flickr, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=4077294

{England, Somerset} A game rearing site with approx. 2.500 9-week-old pheasants. Increased mortality and other clinical signs were reported. Samples were taken and were tested positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6679

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Effectiveness of #BNT162b2 and #mRNA-1273 #JN1-adapted #vaccines against #COVID19-associated #hospitalisation and #death ...

Summary

Background

Little epidemiological evidence exists on the protective effects of the JN.1-adapted mRNA vaccines against COVD-19 hospitalisation and death. In this study, we estimated vaccine effectiveness against COVID-19 hospitalisation and death.

Methods

This nationwide, register-based, cohort study included all Danish residents older than 65 years on Oct 1, 2024. We used Denmark's national COVID-19 surveillance system and comprehensive population-based registers, which are updated daily and linked via the unique civil registration number assigned to all residents. To minimise differences between the comparison groups with regard to vaccination history, participants were required to have completed a primary vaccination course in 2021 and have received the 2023–24 XBB.1.5-adapted vaccine between Oct 1, 2023, and Jan 15, 2024. Participants with a recent recorded infection, or a vaccine dose since the previous season and prior to study start, were excluded. COVID-19 hospitalisation was defined as hospital admissions lasting more than 12 h, with associated ICD-10 primary diagnosis codes B342 or B972 (indicating that COVID-19 was the primary reason for admission) and occurring no earlier than 2 days before, and no later than 14 days after, a positive PCR test. Since cause-of-death data were unavailable, a COVID-19 death was defined as a death due to any cause occurring within 30 days of a positive SARS-CoV-2 PCR test. Participants were followed up from study start on Oct 1, 2024, until Jan 31, 2025, or, if earlier, until their date of death, emigration, first positive SARS-CoV-2 PCR test during follow-up, or further vaccination, whichever occurred first. Hazard ratios comparing event rates among those with and without a JN.1 booster dose during follow-up were derived using Cox regression. Vaccine effectiveness was estimated separately by vaccine brand, time since vaccination, and for the predominant circulating variants KP.3.1.1 and XEC. We used a case-only analysis to assess comparative vaccine effectiveness between the two variants.

Findings

Of nearly 6 million people resident in Denmark on Oct 1, 2024, 1 247 315 were older than 65 years and 894 560 met inclusion criteria and were included in the study. Median age was 76 years (IQR 70–81); 484 735 (54·2%) of 894 560 people were female and 409 825 (45·8%) were male. Among those without JN.1 vaccination, 278 COVID-19 hospitalisations and 84 deaths were observed during 25·6 million person-days compared with 197 COVID-19 hospitalisations and 56 deaths observed during 62·9 million person-days in those vaccinated with BNT162b2 JN.1 and ten COVID-19 hospitalisations and one death observed during 9·2 million person-days in those vaccinated with mRNA-1273 JN.1. Vaccine effectiveness for BNT162b2 JN.1 was 70·2% (95% CI 62·0–76·6) against hospitalisation and 76·2% (63·4–84·5) against death. We found little evidence of waning effectiveness 4 months after vaccination. For mRNA-1273 JN.1, vaccine effectiveness was 84·9% (70·9–92·2%) against hospitalisation and 95·8% (69·2–99·4%) against death; however those vaccinated with mRNA-1273 JN.1 were younger and healthier. The BNT162b2 JN.1 vaccine effectiveness against hospitalisation was 71·7% (44·4–85·6) after infection with KP.3.1.1 and 76·8% (59·0–86·9) after infection with XEC. BNT162b2 JN.1 vaccine effectiveness against death from these variants was 90·9% (67·4–97·5) for KP.3.1.1 and 76·3% (24·7–92·6) for XEC. The case-only analysis found no differential protection.

Interpretation

Both JN.1-adapted vaccines offered high levels of sustained protection for 4 months against hospitalisation and death. These findings support continued use of regularly updated variant-adapted mRNA vaccines in older adults as an effective strategy to reduce severe COVID-19 outcomes.

Funding

None.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00380-9/fulltext?rss=yes

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The combinatorial activities of #oseltamivir and #molnupiravir against #influenza virus infections in vitro and in vivo

Highlights

• Mol shows greater antiviral effects against IAV and IBV in cell cultures.

• Mol and Ose together showed a synergistic effect against IAV.

• In mice, Mol alone or with Ose reduced lung injury and viral load.


Abstract

Oseltamivir, a neuraminidase inhibitor, is widely used in the clinic for treating influenza virus infections. However, suboptimal efficacy and risk of drug resistance development remain major challenges. Molnupiravir, a ribonucleoside analog, was originally developed to treat influenza, but was repurposed and first approved for treating COVID-19 in 2021. Considering their complementary mode-of-actions, this study aimed to investigate the combinatorial activities of oseltamivir and molnupiravir against influenza virus infections. In cell culture models, we found that β-d-N4-hydroxycytidine (NHC), the active form of molnupiravir, exerted more potent antiviral activities against influenza A and B viruses, when compared to oseltamivir treatment. Combination of NHC with oseltamivir exhibited a synergistic antiviral effect against the influenza A/Puerto Rico/8/34 H1N1 strain, but not the influenza B/Washington/02/2019 strain. In a mouse model infected with the PR/8 virus strain, treatment with molnupiravir alone or in combination with oseltamivir effectively attenuated lung injury and reduced viral load in the tissue. Taken together, molnupiravir can be explored in combination with oseltamivir to treat influenza, especially for patients infected with the oseltamivir-resistant strains, whereas further research is warranted.

Source: Virology, https://www.sciencedirect.com/science/article/abs/pii/S0042682225002557?via%3Dihub

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#Biosecurity uptake and perceived #risk of avian #influenza among people in contact with #birds

Abstract

Introduction

Recent intercontinental spread of highly pathogenic avian influenza (HPAI) A(H5N1) among kept and wild birds, and transmission to mammalian hosts, including cattle and humans, has heightened the need to review public health risk assessments. Biosecurity is essential for limiting disease spread, but how widely practices are implemented is not fully known. 

Methods

Here, we report on uptake of biosecurity measures and risk perception of avian influenza virus (AIV) in the context of preventing zoonotic transmission to persons potentially at high risk of exposure. Questionnaire data from 225 people in contact with birds in the UK (Avian Contact Study, May to July 2024) was analysed. 

Results

We found hand washing after contact with birds was the most common biosecurity measure implemented (89%, 196/218), followed by using disinfecting footwear dips (78%, 170/218). Individuals in contact with a higher number of birds were more likely to use at least one PPE measure for the face or body (χ^2 (1, n=217) = 32.452, p<0.001) or at least one footwear-related PPE measure (Df=1, n=217, p<0.001). The perceived risk of AIV to the health of birds was high for individuals in contact with large flocks (≥1001 birds) and associated with uptake of at least one footwear-related PPE measure (χ^2 (1, n=185)= 9.171, p=0.002). Perceived risk of AIV to respondents' own health was low, regardless of the number of birds a respondent had daily contact with. 

Conclusions

Routinely used biosecurity measures are implemented to limit AIV spread among birds, but not with the purpose of limiting zoonotic transmission from birds to humans. Identifying cohort characteristics which could lead to low BM uptake, alongside barriers and facilitators to BM uptake is important for informing zoonotic AIV public health campaigns.


Competing Interest Statement

LES, SG, SM, JT and RP are employees of the UK Health Security Agency. LES receives consultancy fees from the Sanofi group of companies and other life sciences companies. PM is an employee of the Animal Plant and Health Agency. The views expressed are those of the authors and not necessarily those of the UKHSA or the Department of Health and Social Care.

Funding Statement

Funding for the Avian Contact Study was awarded by PolicyBristol from the Research England QR Policy Support Fund (QR PSF) 2022-24 for investigating Zoonotic spillover of avian influenza. AT is funded by the Wellcome Trust, Early Career Award [227041/Z/23/Z]. EBP acknowledges support from the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Evaluation and Behavioural Science at the University of Bristol (NIHR207385).

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.04.23.25326059v2

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Tuesday, July 29, 2025

Genomic profiling of #cefotaxime-resistant #Haemophilus influenzae from #Norway and #Sweden reveals extensive expansion of virulent #MDR international clones

Abstract

Cefotaxime-resistant Haemophilus influenzae (CRHI) are a global concern, but little is known about their molecular epidemiology. The goal of this study was to perform genomic profiling of 191 CRHI from Norway (n = 183) or Sweden (n = 8) (2006–2018) and assess clonal spread using core genome multilocus sequence typing (cgMLST)-based Life Identification Number (LIN) codes based on whole genome sequencing (Ion Torrent). Cefotaxime resistance was confirmed with broth microdilution minimal inhibitory concentration (MIC), interpreted with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. 35.7% of isolates with cefotaxime gradient MIC of 0.25 mg/L were falsely resistant. All but two isolates (blood) were non-invasive, and all but two (serotype f) were non-typeable. Characterization included calling of resistance determinants, ftsI typing (penicillin-binding protein 3, PBP3), and classification of PBP3-mediated beta-lactam resistance (rPBP3), with assignment to rPBP3 stage and group. All isolates had rPBP3-defining substitutions, and 78.5% were stage 3 (L389F positive). Beta-lactam MICs correlated well with rPBP3 genotypes. Significant proportions of stage 3 isolates were cross-resistant to ceftriaxone (86.0%) and meropenem (meningitis breakpoints, 26.0%). The CRHI prevalence in Norway doubled during the study period and approached 1%. A shift from stage 2 to stage 3 rPBP3 in 2011–2012 led to emergence of CRHI with higher beta-lactam MICs and co-resistance to multiple non-beta-lactams, including extensively drug-resistant (XDR) strains. The shift was driven by transformation with two distinct variants of the transpeptidase region and multiclonal expansion. 66.0% of the isolates belonged to 27 clusters. Ten clusters or singletons belonged to international CRHI clones represented in the PubMLST database. The study provides new insight into CRHI evolution, resistance profiles, and clonal dynamics in a period when this phenotype went from exceptional to unusual in Europe. International CRHI clones are described for the first time, including eight high-risk clones associated with invasive disease, calling for enhanced genomic surveillance. LIN coding, supplemented with ftsI typing and rPBP3 staging, is well-suited for definition of CRHI clones. LIN9, defined by ≤ 10 allelic differences, offered the highest resolution level fully supported by maximum likelihood core genome phylogeny and is proposed as a global standard for genomic surveillance of H. influenzae.

Source: Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2025.1601390/full

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Experimental #infection of #alpacas (Vicugna pacos) with #Influenza C and D viruses results in subclinical upper respiratory tract disease

Abstract

Influenza D virus (IDV), a new genus within the Orthomyxoviridae family, was initially detected in pigs and cattle. IDV is structurally similar to influenza C virus (ICV). Influenza A, C and D viruses all have non-human maintenance hosts and likely circulate in several mammalian species. Camelids, as a reservoir for zoonotic viruses, were not extensively studied until the emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. Antibody responses to both ICV and IDV could be detected in dromedary camels from Kenya but not differentiated, owing to cross-reactivity. It was unclear whether these findings reflected a technical issue or suggested a role for camelids in ICV and IDV ecology. In the present study, therefore, alpacas (Vicugna pacos), a camelid species, were experimentally inoculated with ICV (C/Victoria/1/2011) or IDV (D/bovine/France/5920/2014) to assess susceptibility and assess the antibody response. We have demonstrated that alpacas can be experimentally infected with both ICV and IDV with subclinical infection of the upper respiratory tract (URT), suggesting that virus transmission could potentially occur. These findings accord with previous serology results obtained for camelids and indicate a putative role for these species in ICV and IDV ecology.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.28.667103v1

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#Cambodia reports 14th #human case of #H5N1 avian #influenza virus infection in 2025

PHNOM PENH, July 29 (Xinhua) -- A 26-year-old man from northwest Cambodia's Siem Reap province has been confirmed for H5N1 human avian influenza, raising the number of the cases to 14 so far this year, the Ministry of Health said in a statement on Tuesday.

"A laboratory result from the National Institute of Public Health showed on July 26 that the man was positive for H5N1 virus," the statement said.

"The patient has the symptoms of fever, cough, sore throat, stomach ache, and breathing difficulty, and is currently being rescued by a team of doctors," it added.

The victim lives in Kravann village of Siem Reap city.

"Investigations revealed that there were dead chickens near the patient's house and he also culled and plucked chickens three days before he fell ill," the statement said.

Health authorities are looking into the source of the infection and are examining any suspected cases or people who have been in contact with the victim in order to prevent an outbreak in the community.

So far this year, the Southeast Asian country has reported a total of 14 human cases of H5N1 bird flu, with five deaths, according to the Ministry of Health.

Source: Xinhua, https://english.news.cn/asiapacific/20250729/9882ad9fd0eb4ebeba5b9d60295727d1/c.html

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




This case indicates the recurrence of the high pathogenicity avian influenza (HPAI) H5N1 subtype (clade 2.3.4.4b) on a poultry farm in Taiwan. The owner of the poultry farm reported the situation to the local veterinary authority in Yunlin County, and samples were collected on July 10. These samples were sent to the National Reference Laboratory for diagnosis on July 11. Clinical signs included increased mortality rates, reduced appetite, and decreased egg production. On July 13, the outbreak was confirmed as HPAI. Subsequently, 2,616 geese were culled, and comprehensive cleaning and disinfection were conducted on July 21. Farms within a 3-kilometer radius of this location will undergo heightened surveillance and visits for the next 28 days.

Source: WOAH, https://wahis.woah.org/#/in-review/6670

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#SARS-CoV-2 #Remdesivir Exposure Leads to Different Evolutionary Pathways That Converge in Moderate Levels of Drug #Resistance

Abstract

Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC50 and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC50). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance.

Source: Viruses, https://www.mdpi.com/1999-4915/17/8/1055

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Potential #impacts of 2.3.4.4b highly pathogenic #H5N1 avian #influenza virus #infection on Snow #Goose (Anser caerulescens) movement #ecology

Abstract

While wild waterfowl are known reservoirs of avian influenza viruses and facilitate the movement of these viruses, there are notable differences in the response to infection across species. This study explored differential responses to infection with highly pathogenic avian influenza in Snow Geese (Anser caerulescens) located in the California Central Valley. Though H5 antibody prevalence was high across years among birds sampled in the winter (75% in both years via hemagglutination inhibition), these values were even higher among birds sampled in summer that failed to migrate (i.e., August 2023 = 100% and August 2024 = 93% via hemagglutination inhibition). Birds that failed to migrate were also generally lighter than birds sampled in the winter and presented notable damage to cerebrum and cerebellum. In December 2022, a single individual positive for infection with H5N1 at the time of sampling indicated reduced movement during the 14 days following sampling but completed spring migration comparably with uninfected conspecifics. However, while no birds were actively infected during sampling and marking in 2023, two marked geese departed for migration late and one did not migrate at all. Additional banded birds marked in August have been reencountered in scenarios ranging from hunter harvest at a different site over a year later to found dead shortly after banding. Our data indicate that Snow Geese infected with HPAI have the potential to express variable outcomes following infection with highly pathogenic H5N1, ranging from rapid recovery within a migratory season to death. These data also suggest that the abnormal failure of some Snow Geese to migrate from the Central Valley is likely driven by HPAI infection.

Source: PLoS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0328149

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#Statement of the 42nd #meeting of #Polio #IHR #Emergency Committee (#WHO, July 29 '25)



{Excerpts}

The Forty-second meeting of the Emergency Committee under the International Health Regulations (2005) (IHR) on the international spread of poliovirus was convened by the WHO Director-General on 18 June 2025 with committee members and advisers meeting via video conference with affected countries, supported by the WHO Secretariat.  

The Emergency Committee reviewed the data on wild poliovirus (WPV1) and circulating vaccine derived polioviruses (cVDPV) in the context of the global target of interruption and certification of WPV1 eradication by 2027 and interruption and certification of cVDPV2 elimination by 2029. 

Technical updates were received about the situation in the following countries: Afghanistan, Angola, Burkina Faso, Guinea, Nigeria, Pakistan, and Papua New Guinea.

(...)

Conclusion

The Committee unanimously agreed that the risk of international spread of poliovirus continues to constitute a Public Health Emergency of International Concern (PHEIC) and recommended extending the Temporary Recommendations for a further three months.

(...)

Source: World Health Organization, https://www.who.int/news/item/28-07-2025-statement-of-the-forty-second-meeting-of-the-polio-ihr-emergency-committee

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