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

____

#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

____

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

____

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

____

#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

____

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

____

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

____

#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

____

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

____

#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

____

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

____

#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

____

Monday, July 28, 2025

Updated joint #FAO / #WHO / #WOAH public #health #assessment of recent #influenza #H5 virus #events in animals and people (July 28 '25)

 


Key points 

-- At the present time, based on available information, FAO-WHO-WOAH assess the global public health risk of influenza A(H5) viruses to be low, while the risk of infection for occupationally or frequently exposed (e.g., with backyard poultry) persons is low to moderate depending on the risk mitigation and hygiene measures in place and the local avian influenza epidemiological situation. 

-- Transmission between animals continues to occur and, to date, a growing yet still limited number of human infections are being reported. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, the overall public health impact of such infections at a global level, at the present time, is considered minor. The assessment could change if and when additional epidemiological or virological information becomes available. 

-- This risk assessment from FAO, WHO and WOAH updates the assessment of the risk of zoonotic transmission (for example, animal to human) considering additional information made available since the previous assessment of 17 April 2025. 

-- This update is limited to the inclusion of additional information being made available globally. 

-- Due to the potential risk to human health and the far-reaching implications of the disease on the health of wild birds, poultry, livestock and other animal populations, timely notification to global authorities and the use of a One Health approach are essential to: 

- tackle avian influenza effectively, 

- to monitor and characterize virus circulation, 

- to prevent transmission within species and to new species 

- to reduce spread among animals, and 

- to prevent human infections from exposure to animals. 


Infections in animals 

-- To date, H5 avian influenza viruses have been detected in birds and/or mammals across all continents except Oceania. 

-- The predominant H5 virus clades currently circulating worldwide include clades 2.3.2.1 and 2.3.4.4. 

-- Between 1 March and 1 July 2025, an additional 807 A(H5N1) outbreaks in animals (including bird and mammal species) have been reported to WOAH. 

-- Of these, 268 outbreaks occurred in poultry (of any farming system), 389 outbreaks in wild bird and 92 outbreaks occurred in mammalian species. 

-- In Cambodia, 9 out of 14 outbreaks in poultry occurred in the vicinity of reported human cases. 


H5 clade 2.3.2.1 viruses 

-- Since 1 March 2025, clade 2.3.2.1a and 2.3.2.1e (previously classified as a 2.3.2.1c1) viruses have been detected in poultry in Bangladesh and Cambodia, respectively. 

-- Influenza A(H5N1) infections in felids were reported in January 2025 in a wildlife rescue centre in Maharashtra State, India, causing the death of one leopard and three tigers.{2} 

-- Influenza A(H5N1) clade 2.3.2.1a infections were reported in domestic cats and in samples from a live bird market in January 2025 in Madhya Pradesh, India.{3} 

-- The viruses were closely related to A/Victoria/149/2024, a sample identified in a traveller from India to Australia in 2024, which was characterized as a previously unreported reassortant virus consisting of clade 2.3.2.1a, 2.3.4.4b, and wild bird low pathogenicity avian influenza gene segments.{4} 

-- In April 2025, influenza A(H5N1) infections were reported in two captive Serval cats (Leptailurus serval) in Dhaka Division, Bangladesh.{5}   

-- Influenza A(H5N1) outbreaks observed in captive felines in Thailand during 2003-2004 were characterized by severe pneumonia and high mortality and have been associated with the feeding of infected poultry and likely tiger-to-tiger transmission.{6,7} 


H5 clade 2.3.4.4b viruses 

-- Detections of A(H5) in mammals and wild and domestic birds continue to be reported in many countries worldwide. 

-- Clade 2.3.4.4b A(H5) viruses are circulating in wild and domestic birds, have been involved in multiple spillover events affecting wild carnivorous and marine mammals as well as domestic cats and dogs

-- Clade 2.3.4.4b virus infections reported in mammals in the Americas, Asia and Europe have resulted in severe clinical presentation (e.g., pneumonia, myocardial necrosis), with neurological signs (e.g., meningoencephalitis) in some species. {8, 9} 

-- Amino acid changes potentially associated with increased virulence, transmission, or adaptation to mammalian hosts have been sporadically identified.{10,11} 

-- In March 2024, a clade 2.3.4.4b influenza A(H5N1) virus of the B3.13 genotype was detected in unpasteurized milk samples and oropharyngeal swabs from dairy cattle for the first time in the United States of America (USA).{12,13} Since then, influenza A(H5N1) virus detections have continued to be reported through the testing of dairy cattle and bulk milk samples.{14} 

-- Analyses of virus sequence data from infected dairy cattle in the USA indicated that the detections in dairy herds until February 2025 were linked to a single wild bird-to-dairy cow transmission event of a B3.13 genotype clade 2.3.4.4b A(H5N1) virus that occurred in late 2023 or early 2024.{15} 

-- During January-February 2025, the United States Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) National Veterinary Services Laboratories (NVSL) confirmed the detection of a genotype D1.1 H5N1 clade 2.3.4.4b virus in dairy cattle in the states of Nevada and Arizona , representing two additional separate spillover events from birds to cattle.{16,17} The exact mode of the virus introductions into dairy cattle remains unclear.{18} 

-- The genotype D1.1 virus has been the most frequently detected H5N1 genotype across North America in 2025 and has affected wild birds, poultry and  mammals, including wild and domestic felids and a marine mammal

-- Presently, to our knowledge, viruses from the clade 2.3.4.4b A(H5N1) B3.13 and D1.1 genotypes  have not been detected outside of North America in field conditions.  

-- Between March 2024 and 1 July 2025, 1074 dairy cattle herds in 17 states of the USA have tested positive for A(H5N1). Since the last joint assessment of 17 April 2025, the number of H5N1 detections in dairy herds has significantly decreased despite a surge in the State of Idaho during the month of April.{19} 

-- The exact routes of transmission between dairy cattle, and the roles of viremia and protective immunity remain unclear. 

-- While virus shedding in milk seems to be consistently linked with clinical disease, viral RNA has also been found in respiratory and urine samples intermittently and earlier in infection. 

-- Also, while transmission to new herds has been linked with movement of lactating cows, in multiple instances herds without a link to recent movement of lactating cattle have been affected. Some results indicate seroconversion in non-lactating cattle.{20} 

-- Experimental intramammary infection and re-infection of lactating cows with an A(H5N1) B3.13 virus indicated that while the primary inoculation led to mastitis and viral shedding in milk, secondary inoculation in an unaffected quarter, following resolution of infection from the primary inoculation, resulted in neither clinical manifestations nor virus shedding in milk.{21} 

-- Further studies are needed to understand the continued transmission of A(H5N1) in dairy cattle.  

-- In 2025, over 70 confirmed cases of A(H5) infection were reported in domestic cats in the USA across 19 states. Many cases were presumably linked to raw food diets, exposure to dairy farms, or they occurred in indoor-only cats with unknown exposure routes. Infections frequently resulted in severe respiratory and neurological illness, with high mortality. Detections in other mammals continued to be reported as well.{22} 

-- On 11 February 2025, an outbreak in a mixed backyard flock (chickens, ducks and turkeys) in Chaco province, Argentina was reported to the Servicio Nacional de Sanidad y Calidad Agroalimentaria (SENASA). The SENASA reference laboratory deposited the sequences in GISAID database (EPI_ISL_19752381 and EPI_ISL_19823059–68). The phylogenies showed that the A(H5N1) viruses from Argentina collected in 2025 are triple reassortants; the genome resembles that of North American genotypes B3.6 and B3.13, but with the Eurasian PA segment replaced by one from South American low pathogenicity avian influenza viruses.{23} 

-- On 4th March 2025, A(H5N1) virus infection was confirmed in domestic cats on a poultry farm in Belgium. The cats showed severe disease and were euthanized. They were likely infected by consuming contaminated eggs or drinking infected water, although the precise transmission route remains unconfirmed.{24} 

-- On 24 March 2025, the Department for Environment, Food & Rural Affairs (DEFRA) of the United Kingdom reported their first detection of influenza A(H5N1) clade 2.3.4.4b virus in a milk sample from a single sheep in Yorkshire. The case was identified on a premises where high pathogenicity avian influenza (HPAI) viruses had been confirmed in domestic birds in February 2025. This H5N1 virus is different from the ones being detected in dairy cattle in the US.{25} 

-- A(H5)-specific antibodies were also detected in multiple samples from the sheep who lived in close proximity to the infected poultry and on a premises likely heavily contaminated with the virus.{26}  

-- On 12 May (confirmed on 15 May) 2025, A(H5N1) clade 2.3.4.4b viruses were detected on a commercial breeder farm in Montenegro, Rio Grande do Sul, Brazil. Over 17,000 birds on the premises either died or were culled.  Subsequently, several suspected cases were reported, and H5 detections in wild birds were confirmed in several states. 

-- In May 2025, A(H5N1) clade 2.3.4.4b viruses were detected in harbour seals and sea otters in Hokkaido, Japan, during investigations of their mortality. The viral sequences, including the hemagglutinin gene, were very similar or identical to clade 2.3.4.4b viruses detected in wild birds in the region, suggesting likely spillover from avian sources. 

-- For the latest information on avian influenza situation in animals worldwide, see the FAO Global Avian Influenza Viruses with Zoonotic Potential situation update and the WOAH situation reports on HPAI, as well as WOAH’s World Animal Health Information System. 


Detections in humans 

-- Since the last joint assessment of April 2025 and as of 1 July 2025, an additional 16 human cases of infection with A(H5N1) viruses have been detected. Of these, nine were detected in Cambodia, two were detected in Bangladesh and India, and single cases were detected in China, Mexico and Viet Nam

-- Of the nine cases detected in Cambodia, four died. The cases detected in India and Mexico were also fatal. All but two cases reported direct or indirect exposure to domestic birds. The source of infection of the case in Mexico was determined as likely indirect exposure to either domestic or wild birds and the exposure information for one case in India was not available. 

-- No human-tohuman transmission was suspected associated with these confirmed cases. 

-- The viruses from  the case in India and from both cases in Bangladesh belong to HA clade 2.3.2.1a viruses. Viruses from all the cases from Cambodia belong to clade 2.3.2.1e viruses. The viruses from the cases in China and Mexico belong to clade 2.3.4.4b viruses.  


Virus characteristics  

-- Regular monitoring and screening of viral sequences from birds has rarely found markers of mammalian adaptation in A(H5) viruses. Those that have been detected are mainly in the polymerase proteins of the virus. Sporadic mutations in polymerase proteins have been observed more frequently in viruses from mammals. 

-- Additional studies on A(H5N1) genotype B3.13 viruses indicate no differences in receptor binding (retaining a preference for binding to avian-like sialic acid receptors).{27} 

-- Some of the D1.1 genotype viruses detected in dairy cattle have the amino acid mutation D701N in the PB2 protein, which has been associated with increased polymerase activity in mammalian cells. 

-- As of 1 March 2025, this mutation has neither been observed in D1.1 viruses detected in wild birds nor in poultry. The virus from the patient in Wyoming infected with A(H5N1) clade 2.3.4.4b genotype D1.1 had the E627K mutation in the PB2 protein which is associated with more efficient virus replication in mammalian cells.{28} This change has not been observed in any D1.1 viruses which have been detected in dairy cattle, but the E627K mutation has been found in some B3.13 viruses detected in dairy cows.  

-- Available virus sequences from human cases have shown some genetic markers that may reduce susceptibility to neuraminidase inhibitors (antiviral medicines such as oseltamivir) or endonuclease inhibitors (such as baloxavir marboxil). While these changes may reduce antiviral susceptibility in laboratory testing, the clinical impact of these genetic changes requires further studies.{29}  

-- Experimental studies with A(H5N1) clade 2.3.4.4b viruses, including a B3.13 virus from the human case in Texas and a human case from Michigan, have shown variable transmission between ferrets  by direct contact, but no or inefficient transmission via respiratory droplets in most studies.{30,31,32,33,34,35,36}  

-- An unpublished study in ferrets done by the US CDC with a D1.1 A(H5N1) virus (A/Washington/239/2024) did not show transmission via respiratory droplets.{37} 

-- Currently circulating A(H5N1) viruses would need further genetic changes to gain the ability to spread efficiently among humans via respiratory droplets, consistent with the current level of risk to public health, which is low. 

-- Based on limited seroprevalence information available on A(H5) viruses, human population immunity against the HA of A(H5) viruses is expected to be minimal; human population immunity targeting the N1 neuraminidase is found to be present although the impact of this immunity is yet to be understood.{38} 

-- Experimental studies suggest prior A(H1N1) immunity reduced virus replication and disease severity of bovine-derived B3.13 genotype A(H5N1) virus in ferrets and that ferrets with this pre-existing immunity expressed A(H5N1) cross-reacting antibodies to the neuraminidase protein.{39} However, the effectiveness of quadrivalent seasonal influenza vaccine (QIV) against influenza A(H5N1) virus remains a speculation, as a recent study observed no cross-neutralisation of H5N1 viruses by sera from patients vaccinated against seasonal influenza with QIV.{40}  


Candidate vaccine viruses (CVV) 

-- The WHO Global Influenza Surveillance and Response System (GISRS), in collaboration with animal health partners (FAO, WOAH, OFFLU (Joint WOAH-FAO network of expertise on animal influenza) and others), continue to evaluate candidate vaccine viruses for pandemic preparedness purposes both bi-annually and on an ad hoc basis. 

-- Regular genetic and antigenic characterization of contemporary zoonotic influenza viruses are published here with the most recent update on A(H5) CVVs published in February 2025 following the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2025-2026 Northern Hemisphere Influenza Season.  

-- The majority of circulating clade 2.3.4.4b viruses reacted well to at least one of the post-infection ferret antisera raised against the existing CVVs. The majority of the clade 2.3.2.1e viruses characterized antigenically reacted well to ferret antisera raised against the existing and CVV proposed in September 2024. Clade 2.3.2.1a viruses detected recently in poultry and felines in India were not characterized antigenically but had HA genes similar to that of the A(H5N1) virus detected in a traveller returning to Australia from India. This virus reacted poorly with ferret antisera raised again available CVVs, thus a new clade 2.3.2.1a CVV was proposed. A new clade 2.3.4.4h CVV was also proposed due to the ongoing detections of this clade of viruses in poultry in China and continued genetic evolution leading to reduced reactivity to existing CVVs. The updated list of available zoonotic influenza candidate vaccine viruses (CVVs) which include A(H5N1) viruses and potency testing reagents is updated on the WHO website. 


Assessment of current public health risk posed by influenza A(H5N1) viruses{41} 

1. What is the global public health risk of additional human cases of infection with avian influenza A(H5) viruses? 

-- Despite the continued detections of A(H5) viruses in animals and continued human exposures to the virus at the human-animal-environment interface, there have been relatively few human infections reported to date.  Of the human cases of A(H5) detections reported since the beginning of 2021, the vast majority were infections in people associated with exposure to A(H5) viruses through direct or indirect contact with infected animals, or contaminated environments, such as live poultry markets or other premises with infected animals. Severity of illness has ranged from mild to fatal, with the majority of mild cases reported by the USA associated with exposure to infected dairy cattle. Thus far, among the cases, there has been no reported or identified human-to-human transmission through follow up epidemiologic, virologic and serologic investigations. Investigations for some of the cases continue. Current virologic and epidemiologic information indicates that these viruses remain avian influenza viruses without established adaptation to mammalian hosts and have not acquired the capacity for sustained transmission between humans.  The epidemiological situation changed in 2024 with the spread of A(H5) virus in the USA dairy cattle population following an initial spillover event from birds to dairy cattle in 2023/24 followed by two additional spillover events identified in 2025. Persons exposed to affected dairy cattle and other infected animals may be in prolonged and close contact with potentially contaminated surfaces and animal products. As long as A(H5) viruses continue to be detected in wild and domestic birds and mammals, including dairy cattle, and related environments, including in unpasteurized/raw milk, further human cases are expected, particularly amongst exposed individuals not wearing appropriate personal protective equipment and/or in environments where mitigation measures are not in place.  

-- Based on currently available information, FAO-WHO-WOAH assesses the global public health risk of influenza A(H5) viruses as low. Although additional human infections associated with exposure to infected animals or contaminated environments are expected to occur, they remain limited in the general population and the overall current public health impact of such infections at a global level is minor, considering the surveillance, response, mitigation and control measures in place.  

-- However, while the risk of infection to the general public is low, among persons with exposure to infected birds or mammals or contaminated environments, the risk of infection can range from low to moderate, depending on nature of the exposure, the duration of exposure, the consistent and appropriate use of personal protective equipment, and the use of other response, mitigation and control measures particularly in environments where animals are kept.  

-- The pandemic potential of these viruses requires enhanced vigilance, especially in animal populations where animal to animal transmission is known to occur, and close monitoring in animals and humans. It remains essential that, while farmers enhance biosecurity on their farms, governments should focus efforts on strengthening surveillance in susceptible animal populations and in persons exposed to infected animals. 

-- In addition to prevention and mitigation  efforts to reduce and/or stop animal to animal transmission and reduce environmental contamination. Furthermore, prevention efforts to stop animals to human transmission and to improve risk communication and community engagement in particular to those occupationally exposed or with backyard poultry and training in the use of personal protective equipment are key to preventing new human infection with these viruses. 


2. What is the likelihood of human-to-human transmission of avian influenza A(H5) viruses?  

-- There has been no reported human-to-human transmission of A(H5) viruses since 2007, although there may be knowledge gaps in investigations around identified human infections. In 2007 and the years prior, small clusters of A(H5) virus infections in humans were reported, including limited human to human transmission from patients to health care workers. Since then, sustained human-to-human transmission of A(H5) viruses has not been reported.{42}  

-- The A(H5) viruses currently detected in mammals, including in human cases, largely retain genomic and biological characteristics of avian influenza viruses and remain well-adapted to spread among birds. Except for within-host acquired amino acid mutations in polymerase proteins, there is still limited evidence for adaptation to mammals and humans even when transmission in non-human mammals has been suspected.{43} 

-- No changes in receptor binding tropism have been consistently observed that would increase binding to receptors in the human upper respiratory tract which is one of several adaptations required to increase the probability of transmission to and among people. In addition, available preliminary sero-studies and seroinvestigations have not identified human-to-human transmission of A(H5N1) in the USA. Therefore, sustained human-to-human transmission of the currently circulating A(H5) viruses is considered unlikely without further genetic changes in the virus. This is actively being assessed by agencies in affected Member States, FAO, WHO, WOAH and partners. WHO, together with FAO and WOAH, continues to evaluate A(H5) viruses closely and will reassess the risk associated with the currently circulating A(H5) viruses as more information becomes available.  

-- Further antigenic characterization of A(H5) viruses, including in relation to the existing CVVs, and development of specific reagents are being prioritized at the WHO Collaborating Centres and Essential Regulatory Laboratories of GISRS in collaboration with public health, animal health, and veterinary sector colleagues.  


Confidence level of the assessment 

-- The overall confidence in the risk assessment is considered medium. The information used is derived from reports from national animal and human health authorities. There may be biases in surveillance, testing and reporting. Although the results and conclusions from peer-reviewed publications, pre-print publications and unpublished data informed this risk assessment, no systematic literature review was undertaken. Critical knowledge gaps remain in the understanding of the epidemiology. 


Recommended actions  

-- It is recommended that Member States and national authorities: 

increase surveillance and vigilance, in human populations, especially amongst occupationally exposed persons, for the possibility of zoonotic infections, particularly through National Influenza Centres (NICs) and other influenza laboratories associated with GISRS; 

assess and reduce the risk among occupationally exposed persons using methods such as active case finding and molecular and serologic methods, reducing environmental exposures, providing adequate and appropriate personal protective equipment; 

conduct active case finding around suspected and confirmed human cases to determine if there are additional cases or indications of human-to-human transmission; and   

work with national agencies and partners to better understand the exposure to and risk from raw/unpasteurized milk and milk products.  

-- Under the International Health Regulations (IHR) (2005),{44} States Parties are required to notify WHO within 24 hours of any laboratory-confirmed case of human influenza caused by a new subtype according to the WHO case definition.{45} 

-- WHO has published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005).{46}  

-- Member States and national authorities are also recommended to: 

increase surveillance and timely reporting efforts for the early detection of A(H5) influenza viruses in domestic birds, wild birds and mammals{47}; 

include infection with an A(H5) influenza virus as a differential diagnosis, in non-avian species, including cattle, swine and other livestock and farmed domestic and wild animal populations, with high likelihood of exposure to A(H5) viruses; 

implement preventive and early response measures to break the chain of infection among domestic animals (for example, poultry and dairy cattle), including considering the use of vaccination to reduce circulation in poultry as per national policies and according to guidance provided by animal health organizations{48,49}; 

promptly report high pathogenicity avian influenza (HPAI) events in all animal species, including cattle (according to the WOAH case definition{50}) and other domestic and wild mammals, to WOAH and other international organizations such as FAO;  

conduct genetic sequencing and share genetic sequences of influenza viruses and associated metadata in publicly available databases; 

protect animals by mitigating the risk of introduction and spread of the disease through implementation and/or strengthening biosecurity in livestock holdings/premises and along the value chain; 

protect persons by employing good production and hygiene practices when handling animals and animal products; and 

protect persons in contact with suspected/infected animals by providing appropriate personal protective equipment and communicating and educating on the importance and proper use of personal protective equipment and providing information and access to testing. 

(...)

-- Additional studies/surveillance, applying One Health principles are warranted, which could provide information to enhance confidence in the risk assessment. These may include serological studies in high-risk animal populations, in high-risk human populations, and epidemiological investigations.  Anyone who may have been exposed to infected or potentially infected animals or contaminated environments should be advised to promptly seek health care if they feel unwell, and to inform their health care provider of their possible exposure. Following prompt testing, early and appropriate clinical management should be initiated, and precautionary measures put in place to assess and prevent potential further spread among humans and animals.  

-- Clinicians should also be alerted to potential zoonotic infection in patients with an exposure history to birds or animals especially in areas where A(H5N1) viruses are known or suspected to be circulating in animals but also in areas where surveillance in animals may be limited.  

-- Routine epidemiologic and virologic surveillance for influenza should be conducted ideally yearround using a standard case definition in healthcare facilities according to WHO guidance.{51}  

-- Timely sharing of information and sequence data from both the human and animal health sectors from all regions should continue to be strongly recommended and is critical for rapid and robust joint risk assessment. 

-- The rapid sharing of virus materials with WHO Collaborating Centres of GISRS continues to be essential to conduct a thorough risk assessment and develop or adjust targeted response measures. 

-- 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.{52} 

-- Data pertaining to the risk elements within TIPRA should be generated and shared with WHO.  

-- Efforts to reduce human exposure to birds, livestock, and other mammals infected with or potentially infected with avian and other animal influenza viruses should be implemented and enhanced to minimize the risk of zoonotic infections. 

-- Individuals with activities that involve exposure to infected animals and/or contaminated environments are at higher risk and should take necessary precautions to prevent infection.{53} 

-- Those who are exposed to potentially infected animals should have access to, be trained in their use under different environmental conditions, and wear personal protective equipment including eye protection.{54} 

-- If they develop respiratory symptoms or conjunctivitis, they should be rapidly tested, and precautionary infection control measures should be put in place to prevent potential further spread among humans and to animals. 

-- For detailed guidance on treatment, refer to relevant global and national guidance.{55} 

-- Some manufacturers have initiated production of an A(H5) human vaccine that matches current circulating strains. Although a few countries are procuring vaccine to vaccinate occupationally exposed persons, this is not currently being recommended as a global strategy considering the limited number of human infections with A(H5N1) 2.3.4.4b viruses.  

-- Investigations are ongoing to understand the risk to humans from consuming raw/unpasteurized milk contaminated with A(H5N1) virus. FAO, WHO and WOAH advise consuming pasteurized milk, instead of raw/unpasteurized milk. 

-- Due to the potential health risks from many dangerous zoonotic pathogens, raw/unpasteurized milk consumption should be avoided.{56} If pasteurized milk is not available, heating raw milk until it boils makes it safer for consumption.{57}  

-- More information will be available as investigations are actively ongoing in the USA and elsewhere. WHO and GISRS, jointly with FAO, WOAH and OFFLU are working closely together to continuously assess the avian influenza situation. This includes increased surveillance and testing to monitor the evolution and geographic spread of avian influenza viruses, including A(H5N1) viruses, to provide timely and updated joint risk assessments.  


References 

{1} Formerly classified as A(H5) clade 2.3.2.1c. Ort JT, Zolnoski SA, Lam TT, Neher R, Moncla LH. Development of avian influenza A(H5) virus datasets for Nextclade enables rapid and accurate clade assignment. bioRxiv [Preprint]. 2025 Feb 3:2025.01.07.631789. doi.org/10.1101/2025.01.07.631789. 

{2} WOAH. Report from World Animal Health Information System (WAHIS). wahis.woah.org/#/inreview/6218?reportId=171807&fromPage=event-dashboard-url

{3} Raut AA, Aasdev A, Kumar N, Pathak A, Mishra A, Sehgal P et al. Highly Pathogenic Avian Influenza A (H5N1) Clade 2.3.2.1a virus infection in domestic cats, India, 2025. bioRxiv 2025.02.23.638954; doi:  doi.org/10.1101/2025.02.23.638954. 

{4} Deng YM, Wille M, Dapat C, Xie R, Lay O, Peck H et al. Influenza A(H5N1) Virus Clade 2.3.2.1a in Traveler Returning to Australia from India, 2024. Emerg Infect Dis. 2025 Jan;31(1):135-138. doi.org/10.3201/eid3101.241210. 

{5} WOAH. Report from World Animal Health Information System (WAHIS). wahis.woah.org/#/inreview/6453?reportId=174033&fromPage=event-dashboard-url

{6} Thanawongnuwech R, Amonsin A, Tantilertcharoen R, Damrongwatanapokin S, Theamboonlers A, Payungporn S, et al. Probable Tiger-to-Tiger Transmission of Avian Influenza H5N1. Emerg Infect Dis. 2005;11(5):699-701. doi.org/10.3201/eid1105.050007. 

{7} Keawcharoen J, Oraveerakul K, Kuiken T, Fouchier R, Amonsin A, Payungporn S, et al. Avian Influenza H5N1 in Tigers and Leopards. Emerg Infect Dis. 2004;10(12):2189-2191. doi.org/10.3201/eid1012.040759. 

{8} Elsmo EJ, Wünschmann A, Beckmen KB, Broughton-Neiswanger LE, Buckles EL, Ellis J, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Clade 2.3.4.4b Infections in Wild Terrestrial Mammals, United States, 2022. Emerg Infect Dis. 2023;29(12):2451-2460. doi.org/10.3201/eid2912.230464. 

{9} Plaza PI, Gamarra-Toledo V, Euguí J, Lambertucci SA. Recent Changes in Patterns of Mammal Infection with Highly Pathogenic Avian Influenza A(H5N1) Virus Worldwide. Emerg Infect Dis. 2024;30(3):444-452. doi.org/10.3201/eid3003.231098. 

{10} Puryear W, Sawatzki K, Hill N, Foss A, Stone JJ, Doughty L, et al. Highly Pathogenic Avian Influenza A(H5N1) Virus Outbreak in New England Seals, United States. Emerg Infect Dis. 2023;29(4):786-791. doi.org/10.3201/eid2904.221538. 

{11} Uhart MM, Vanstreels RET, Nelson MI, Olivera V, Campagna J, Zavattieri V et al. Epidemiological data of an influenza A/H5N1 outbreak in elephant seals in Argentina indicates mammal-to-mammal transmission. Nat Commun 15, 9516 (2024). doi.org/10.1038/s41467-024-53766-5. 

{12} Lee D, Bahl J, Torchetti M, Killian M, Ip HS, DeLiberto TJ, et al. Highly Pathogenic Avian Influenza Viruses and Generation of Novel Reassortants, United States, 2014–2015. Emerg Infect Dis. 2016;22(7):1283-1285. doi.org/10.3201/eid2207.160048.  

{13} United States Department of Agriculture (USDA). Federal and State Veterinary, Public Health Agencies Share Update on HPAI Detection in Kansas, Texas Dairy Herds. 25 March 2024. www.aphis.usda.gov/news/agencyannouncements/federal-state-veterinary-public-health-agencies-share-update-hpai

{14} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. www.aphis.usda.gov/livestockpoultry-disease/avian/avian-influenza/hpai-detections/livestock

{15} Nguyen T-Q, Hutter C, Markin A, Thomas M, Lantz K, Killian ML et al. Emergence and interstate spread of highly pathogenic avian influenza A(H5N1) in dairy cattle. bioRxiv 2024.05.01.591751; doi.org/10.1101/2024.05.01.591751. 

{16} USDA. APHIS Confirms D1.1 Genotype in Dairy Cattle in Nevada, 31 Jan 2025. www.aphis.usda.gov/news/program-update/aphis-confirms-d11-genotype-dairy-cattle-nevada-0.   

{17} USDA. APHIS Identifies Third HPAI Spillover in Dairy Cattle, 13 Feb 2025. www.aphis.usda.gov/news/program-update/aphis-identifies-third-hpai-spillover-dairy-cattle.  

{18} Lowen AC, Baker AL, Bowman AS, García-Sastre A, Hensley SE, Lakdawala SS et al. 2025. Pandemic risk stemming from the bovine H5N1 outbreak: an account of the knowns and unknowns. J Virol 99:e00052-25. doi.org/10.1128/jvi.00052-25. 

{19} USDA. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock. www.aphis.usda.gov/livestockpoultry-disease/avian/avian-influenza/hpai-detections/livestock

{20} Lombard J, Stenkamp-Strahm, McCluskey B, Abdul-Hamid C, Cardona C, Petersen B et al. Invited review: The One Health challenges and opportunities of the H5N1 outbreak in dairy cattle in the United States, Journal of Dairy Science, Volume 108, Issue 7, 2025, Pages 6513-6537, ISSN 0022-0302, doi.org/10.3168/jds.2024-26222. 

{21} Facciuolo A, Aubrey L, Barron-Castillo U, Berube N, Norleen C, McCreary S et al. Dairy cows develop protective immunity against reinfection with bovine H5N1 influenza virus. Nat Microbiol 10, 1366–1377 (2025). doi.org/10.1038/s41564-025-01998-6. 

{22} USDA. Detections of Highly Pathogenic Avian Influenza in Mammals. 26 June 2025. Available at: https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/mammals

{23} Vanstreels RET, Nelson MI, Artuso MC, Marchione VD, Piccini LE, Benedetti E et al. Novel Highly Pathogenic Avian Influenza (A)H5N1 Triple Reassortant in Argentina, 2025. Available at: doi.org/10.1101/2025.05.23.655175. 

{24} Agence fédérale pour la sécurité de la chaîne alimentaire. Communiqué de presse conjoint de l'AFSCA, Sciensano et du SPF Santé publique, Sécurité de la Chaîne alimentaire et Environnement, 4 Mar 2025. favvafsca.be/fr/publication/communique-de-presse-conjoint-de-lafsca-sciensano-et-du-spf-sante-publiquesecurite-de-la-chaine. 

{25} Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency. Influenza of avian origin confirmed in a sheep in Yorkshire, 24 Mar 2025. www.gov.uk/government/news/influenza-of-avianorigin-confirmed-in-a-sheep-inyorkshire#:~:text=The%20UK's%20Chief%20Veterinary%20Officer,been%20confirmed%20in%20captive%20bir ds.   

{26} Banyard AC, Coombes H, Terrey J, McGinn N, Seekings J, Clifton B et al. Detection of clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus in a sheep in Great Britain, 2025. doi.org/10.1101/2025.06.27.661969. 

{27} Yang J, Qureshi M, Kolli R, Peacock TP, Sadeyen J-R, Carter T et al. The Haemagglutinin Gene of Bovine Origin H5N1 Influenza Viruses Currently Retains an Avian Influenza Virus phenotype.  doi.org/10.1101/2024.09.27.615407. 

{28} US CDC. CDC A(H5N1) Bird Flu Response Update February 26, 2025. www.cdc.gov/bird-flu/spotlights/h5n1response-02262025.html

{29} US CDC. CDC A(H5N1) Bird Flu Response Update November 18, 2024. www.cdc.gov/bird-flu/spotlights/h5n1response-11152024.html

{30} US CDC. CDC Reports A(H5N1) Ferret Study Results. 7 June 2024. www.cdc.gov/bird-flu/spotlights/ferretstudy-results.html

{31} Pulit-Penaloza JA, Brock N, Belser JA, Sun X, Pappas C, Kieran TJ et al. Highly pathogenic avian influenza A(H5N1) virus of clade 2.3.4.4b isolated from a human case in Chile causes fatal disease and transmits between co-housed ferrets. Emerg Microbes Infect. 2024 Mar 17:2332667. doi.org/10.1080/22221751.2024.2332667. 

{32} Eisfeld AJ, Biswas A, Guan L, Gu C, Maemura T, Trifkovic S et al. Pathogenicity and transmissibility of bovine H5N1 influenza virus. Nature (2024). doi.org/10.1038/s41586-024-07766-6. 

{33} Restori KH, Septer KM, Field CJ, Patel DR, VanInsberghe D, Raghunathan V et al. Risk assessment of a highly pathogenic H5N1 influenza virus from mink. Nat Commun 15, 4112 (2024). doi.org/10.1038/s41467-02448475-y. 

{34} Pulit-Penaloza JA, Belser JA, Brock N, Kieran TJ, Sun X, Pappas C et al. Transmission of a human isolate of clade 2.3.4.4b A(H5N1) virus in ferrets. Nature. Published online October 28, 2024. doi.org/10.1038/s41586024-08246-7. 

{35} Gu C, Maemura T, Guan L, Eisfeld AJ, Biswas A, Kiso M et al. A human isolate of bovine H5N1 is transmissible and lethal in animal models. Nature (2024). doi.org/10.1038/s41586-024-08254-7. 

{36} Brock N, Pulit-Penaloza JA, Belser JA, Pappas C, Sun X, Kieran TJ, et al. Avian Influenza A(H5N1) Isolated from Dairy Farm Worker, Michigan, USA. Emerg Infect Dis. 2025;31(6):1253-1256. doi.org/10.3201/eid3106.250386. 

{37} US CDC. Influenza Risk Assessment Tool (IRAT) - Virus Report. Highly pathogenic avian influenza A(H5N1) virus; clade 2.3.4.4b Viruses: A/California/147/2024 and A/Washington/239/2024. Date of Evaluation: March 14, 2025. www.cdc.gov/pandemic-flu/media/pdfs/2025/IRATA-California-Washington.pdf 

{38} Daulagala P, Cheng S, Chin A, Luk L, Leung K, Wu JT, et al. Avian Influenza A(H5N1) Neuraminidase Inhibition Antibodies in Healthy Adults after Exposure to Influenza A(H1N1)pdm09. Emerg Infect Dis. 2024;30(1):168171. doi.org/10.3201/eid3001.230756. 

{39} Le Sage V, Werner BD, Merrbach GA, Petnuch SE, O'Connell AK, Simmons HC et al. Pre-existing H1N1 immunity reduces severe disease with bovine H5N1 influenza virus. bioRxiv [Preprint]. 2024 Oct 23:2024.10.23.619881. https://doi.org/10.1101/2024.10.23.619881  

{40} Stevenson-Leggett P, Adams L, Greenwood D, Lofts A, Libri V, Williams B, et al. Investigation of Influenza A(H5N1) Virus Neutralization by Quadrivalent Seasonal Vaccines, United Kingdom, 2021–2024. Emerg Infect Dis. 2025;31(6):1202-1206. doi.org/10.3201/eid3106.241796.  

{41} WHO. (2012). Rapid risk assessment of acute public health events. iris.who.int/handle/10665/70810.  

{42} US CDC. Past Examples of Probable Limited, Non-Sustained, Person-to-Person Spread of Avian Influenza A Viruses. www.cdc.gov/bird-flu/php/avian-flu-summary/h5n1-humaninfections.html?CDC_AAref_Val=https://www.cdc.gov/flu/avianflu/h5n1-human-infections.htm

{43} US CDC. Technical Update: Summary Analysis of Genetic Sequences of Highly Pathogenic Avian Influenza A(H5N1) Viruses in Texas, 2 April 2024. www.cdc.gov/bird-flu/spotlights/h5n1-analysis-texas.html.  

{44} International Health Regulations (2005). Third edition. Geneva: World Health Organization; 2016. iris.who.int/handle/10665/246107

{45} Case definitions for the four diseases requiring notification to WHO in all circumstances under the IHR (2005). Geneva: World Health Organization; 2009. www.who.int/publications/m/item/case-definitions-for-thefour-diseases-requiring-notification-to-who-in-all-circumstances-under-the-ihr-(2005)

{46} WHO case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005). Geneva: World Health Organization; 2024. www.who.int/teams/global-influenza-programme/avianinfluenza/case-definitions

{47} El Masry I, Delgado AH, Silva GOD, Dhingra M, Lyons NA. 2024. Recommendations for the surveillance of influenza A(H5N1) in cattle – With broader application to other farmed mammals. FAO Animal Production and Health Guidelines, No. 37. Rome, FAO. doi.org/10.4060/cd3422en. 

{48} OFFLU Avian Influenza Vaccine Matching (AIM) for poultry vaccines: H5Nx executive summary, October 2024. www.offlu.org/wp-content/uploads/2024/11/OFFLU-Avian-Influenza-Vaccine-Matching-final-clean.pdf

{49} WOAH. Avian influenza vaccination: why it should not be a barrier to safe trade, December 2023. www.woah.org/app/uploads/2023/12/en-woah-policybrief-avianinfluenzavaccinationandtrade.pdf

{50* WOAH. Case definition for infection of bovines with influenza a viruses of high pathogenicity in poultry (high pathogenicity avian influenza in cattle), 26 March 2025. www.woah.org/en/document/case-definition-hpai-cattle/

{51} WHO. Implementing the integrated sentinel surveillance of influenza and other respiratory viruses of epidemic and pandemic potential by the Global Influenza Surveillance and Response System: standards and operational guidance. Geneva: World Health Organization; 2024. iris.who.int/handle/10665/379678.  

{52} WHO. Tool for influenza pandemic risk assessment. www.who.int/teams/global-influenzaprogramme/avian-influenza/tool-for-influenza-pandemic-risk-assessment-(tipra)

{53} US CDC. Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public Health Investigations, 26 Dec 2024. www.cdc.gov/bird-flu/prevention/hpaiinterim-recommendations.html

{54} Animal and Plant Health Inspection Service, USDA. APHIS Recommendations for Highly Pathogenic Avian Influenza (HPAI) H5N1 Virus in Livestock For Workers, 12 April 2024. www.aphis.usda.gov/sites/default/files/recommendations-workers-hpai-livestock.pdf

{55} Guidelines for the clinical management of severe illness from influenza virus infections. Geneva: World Health Organization; 2022. apps.who.int/iris/handle/10665/352453

{56} FAO. Preliminary rapid risk assessment of foodborne avian influenza A (H5N1) virus. openknowledge.fao.org/server/api/core/bitstreams/ca83524e-b3f9-4abe-b52b-dea213227fcf/content

{57} Joint FAO/WHO Codex Alimentarius Commission. Codex Alimentarius: Code of hygienic practice for milk and milk products. www.fao.org/fileadmin/user_upload/livestockgov/documents/CXP_057e.pdf


DISCLAIMER 

The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization (WHO), the Food and Agriculture Organization of the United Nations (FAO) or of the World Organisation for Animal Health (WOAH) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. All reasonable precautions have been taken by WHO, FAO and WOAH to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO, FAO and WOAH be liable for damages arising from its use. 

©FAO, WHO, WOAH, 2025 Some rights reserved. This work is available under a CC BY-NC-SA 3.0 IGO licence. 

Source: World Health Organization, https://www.who.int/publications/m/item/updated-joint-fao-who-woah-public-health-assessment-of-recent-influenza-a(h5)-virus-events-in-animals-and-people-july2025

____

#SARS-CoV-2 #rebound and post-acute #mortality and hospitalization among patients admitted with #COVID19: cohort study

Abstract

Recent investigations have demonstrated a relationship between the persistence of SARS-CoV-2 and post-COVID-19 conditions. Building upon a potential connection between SARS-CoV-2 persistence and early virologic rebound, we examine the association of early virologic rebound with post-acute mortality and hospitalization due to post-acute sequelae among hospitalized patients with COVID-19 in Hong Kong. Our study includes 13,859, 3959, and 4502 patients in the all-patient, nirmatrelvir/ritonavir, and molnupiravir group, respectively. Results show that patients who experienced virologic rebound exhibited a significantly higher risk of post-acute mortality (hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.36–1.70) with a risk difference [RD] of 7.19%, compared with patients without virologic rebound. A similar increase in the risk of post-acute mortality is also observed in nirmatrelvir/ritonavir-treated patients (HR, 1.78; 95% CI, 1.41–2.25; RD, 12.55%) and molnupiravir-treated patients (HR, 1.47; 95% CI, 1.18–1.82; RD, 4.90%). The virologic rebound may thus serve as an early marker for post-COVID-19 condition, enabling healthcare officials to monitor and provide timely intervention for long COVID.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61737-7

____

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

 


Backyard poultry operation in Chobe Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6676

____

Sunday, July 27, 2025

Primary #bovine embryonic #fibroblasts support seasonal #influenza A virus #infection and demonstrate variable #fitness of #HPAI #H5N1

Abstract

The emergence of highly pathogenic avian influenza (HPAI) H5N1 (clade 2.3.4.4b, genotype B3.13) in dairy cattle presents substantial challenges to the agricultural sector and public health. Mechanistic studies of infection and transmission in cattle have proven difficult due to animal handling restrictions as well as limited availability of established cell culture models. Primary Bovine Embryonic Fibroblasts (BeEFs) were collected from a Montana cow and are investigated here as a model to study influenza A virus (IAV) infection dynamics. We compared sialylation profiles, infectious virus production, viral replication, and plaque morphology in both BeEFs and chicken DF-1 cells following infection with the bovine HPAI H5N1 and an earlier 2.3.4.4b genotype (B1.1) isolated in 2022. The data presented here show increased viral fitness of the bovine origin HPAI H5N1 strains across multiple species and bovine susceptibility to human seasonal IAV. This study highlights the ability of BeEFs to serve as a model for studying IAV infections in bovine hosts.


Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

United States Department of Agriculture, https://ror.org/01na82s61, 35208-11567

Montana Agricultural Experiment Station (MAES), MONB00443

HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID), R21 AI178432-01, N7593021C00045

HHS | NIH | National Institute of General Medical Sciences (NIGMS), P20GM12549

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.26.666677v1

____

The Judgment of Paris, Peter Paul Rubens (c.1636)

 


Public Domain.

Source: WikiArt, https://www.wikiart.org/en/peter-paul-rubens/the-judgment-of-paris-1636

____

My New Space

Most Popular Posts