Friday, June 6, 2025

Immediate #PB2-E627K amino acid #substitution after single #infection of highly pathogenic avian #influenza #H5N1 clade 2.3.4.4b in mice

Abstract

The highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b has rapidly disseminated globally, with mammalian infections reported in multiple species. Recent evidence of mammal-to-mammal transmission has heightened concerns about the virus’s potential adaptation to mammals. The polymerase basic 2 (PB2) protein E627K mutation appears to be of key importance for mammalian adaptation. We isolated an HPAI H5N1 clade 2.3.4.4b virus from wild birds in Korea with 96% E and 4% K at amino acid position 627 of PB2. To investigate the genomic characteristics of this clade regarding mammalian adaptation, we studied the replication and transmission of the H5N1 virus in mice. Two experiments with different challenge-to-contact ratios were conducted to assess transmission dynamics and mutation development. In experiment 1, a 4:1 challenge-to-contact ratio resulted in 100% transmission among direct-contact mice, with all mice succumbing to the infection. In experiment 2, a 1:1 ratio yielded 50% transmission, with all challenged mice also succumbing. High viral loads were observed in the lungs and brains in both experiments, with viral titers increasing over time. Notably, the PB2-E627K variant, initially present at 4% in the virus stock, was selected and reached near-fixation (~ 100%) in the lungs and brains by 6 days post-challenge and was subsequently transmitted. No other mammalian-adaptive mutations were identified, emphasizing the pivotal role of PB2-E627K in early stages of mammalian adaptation. These findings highlight the need for continuous genomic monitoring to detect mammalian adaptation markers and assess interspecies transmission risks.

Source: Virology Journal, https://virologyj.biomedcentral.com/articles/10.1186/s12985-025-02811-w

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Chimeric #hemagglutinin and #M2 #mRNA #vaccine for broad #influenza subtype protection

Abstract

Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries. In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells. Moreover, Fluaxe immunization inhibited the inflammatory response induced by influenza infection. In summary, we conclude that Fluaxe can elicit broad cross-protection against numerous influenza subtypes.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01178-x

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Thursday, June 5, 2025

Genetic diversity of #H9N2 avian #influenza viruses in #poultry across #China and implications for #zoonotic transmission

Abstract

Nationwide surveillance of avian influenza viruses (AIVs) in live poultry markets across China has occurred since 2014, providing a resource for AIV prevalence and genetic diversity studies. Here we report that 3,237 of 18,425 samples from poultry were AIV positive (17.57%) between 2019 and 2023, with H9N2 being the dominant subtype. We developed an automated phylogeny-based nomenclature system to classify genetic clades of the dominant H9N2 lineage, the BJ94 lineage. Using this model, we found that ten haemagglutinin (HA) sub-subclades cocirculated in poultry and showed antigenic variation. In addition, 99.46% and 96.17% of H9N2 AIVs in 2021–2023 possessed human-receptor binding-related HA-L226 and human MxA-resistance-related NP-N52 mutations, respectively. H9N2 strains with these two mutations preferred human-type receptors and increased replication in human cells in vitro, regardless of the presence of PB2-V/K/E627. Moreover, H9N2 AIVs containing HA-L226, PB2-V/K627 and NP-N52 were transmitted from infected to naive guinea pigs and ferrets through direct contact and respiratory droplet. This highlights the potential zoonotic risks of H9N2 AIVs.

Source: Nature Microbiology, https://www.nature.com/articles/s41564-025-02002-x

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No evidence of immune #exhaustion after repeated #SARS-CoV-2 #vaccination in vulnerable and healthy populations

Abstract

Frequent SARS-CoV-2 vaccination in vulnerable populations has raised concerns that this may contribute to T cell exhaustion, which could negatively affect the quality of immune protection. Herein, we examined the impact of repeated SARS-CoV-2 vaccination on T cell phenotypic and functional exhaustion in frail older adults in long-term care (n = 23), individuals on immunosuppressive drugs (n = 10), and healthy adults (n = 43), in Canada. Spike-specific CD4+ and CD8+ T cell levels did not decline in any cohort following repeated SARS-CoV-2 vaccination, nor did the expression of exhaustion markers on spike-specific or total T cells increase. T cell production of multiple cytokines (i.e. polyfunctionality) in response to the spike protein of SARS-CoV-2 did not decline in any cohort following repeated vaccination. None of the cohorts displayed elevated levels of terminally differentiated T cells following multiple SARS-CoV-2 vaccinations. Thus, repeated SARS-CoV-2 vaccination was not associated with increased T cell exhaustion in older frail adults, immunosuppressed individuals, or healthy adults.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-60216-3

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qRT-PCR #Detection of Inactivated #H5 Avian #Influenza Virus in Raw #Milk Samples by Miniaturized Instruments Designed for On-Site Testing

Abstract

Highly pathogenic avian influenza virus (HPAIV) of H5 and H7 subtypes has emerged as one of the most important zoonotic pathogens in the 21st century with significant economic consequences. The recent outbreak of H5N1 avian influenza (AI) in dairy cattle highlighted the importance of early detection in managing and mitigating HPAIV outbreaks. A successful high-speed diagnostic response requires rapid site and specimen access, minimal time for test protocols, and prompt communication of the diagnostic results to government officials. A new diagnostic paradigm that consists of miniaturized extractor and qPCR instruments (EZextractor and EZcycler MiniQ), designed for mobile, on-site testing has been compared with a platform of benchtop instruments (QIAGEN RNeasy and QuantStudio 5) for detecting inactivated H5 avian influenza virus (AIV) spiked in raw milk samples. Two sets of experiments were performed: 1) 15 raw milk samples, obtained from 15 different farms, diluted with phosphate-buffered saline and spiked with the virus to reach approximately 10 copies/mcL virus concentration, and 2) raw milk samples from two farms, each spiked with the inactivated AIV H5 followed by 5 series of dilution to reach AIV concentrations of 1000, 100, 10, 1 and 0.1 copies/mcL. Results show that despite the inhibitors in raw milk, AIV in all samples can be detected by both platforms. The MT platform showed higher sensitivity than the benchtop platform: the Ct values from the MT were ~2 units lower than the benchtop Ct values. Our findings demonstrate the robustness of the MT platform for diagnosing AIV H5 in raw milk samples and support its use as an on-site diagnostic for rapid surveillance and response.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.02.657307v1

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#Corynebacterium diphtheriae #Outbreak in #Migrant Populations in #Europe

Abstract

Background

A surge of cases of Corynebacterium diphtheriae infection was observed in reception centers for migrants in Europe beginning in the summer of 2022. Most of the cases were cutaneous, although some respiratory cases as well as one death were reported. A pan-European consortium was created to assess the clinical, epidemiologic, and microbiologic features of this outbreak.

Methods

We assessed cases of toxigenic C. diphtheriae infection that were reported in 10 European countries from January through November 2022. Data regarding countries of origin and transit routes were obtained from interviews with the patients. Whole-genome sequencing and antimicrobial-susceptibility testing were performed on bacterial isolates that were obtained from the patients. The phylogenetic relationships of the isolates and their antimicrobial-resistance genes were evaluated.

Results

A total of 363 toxigenic C. diphtheriae isolates were identified among 362 patients during the study period. Clinical data were available for 346 patients (95.6%): 268 (77.5%) had cutaneous diphtheria, 53 (15.3%) had respiratory diphtheria (11 [3.2%] had a pseudomembrane), and 9 (2.6%) had both respiratory and cutaneous symptoms. Four major genetic clusters were identified, which indicated the multiclonal nature of the outbreak. The ermX gene (which codes for erythromycin resistance) and the pbp2m and blaOXA-2 genes (which code for beta-lactam resistance) were detected in a subgroup of isolates. Isolates that carried ermX were resistant to erythromycin, and isolates that carried pbp2m were resistant to penicillin but were susceptible to amoxicillin. On the basis of the genomic variation within the four genetic clusters, their most recent common ancestors were estimated to have existed between 2017 and 2020.

Conclusions

The distribution of each genetic cluster of C. diphtheriae isolates across multiple countries in Europe showed repeated cross-border spread. The large number of C. diphtheriae infections among migrants is a cause for concern, particularly given that antimicrobial-resistance phenotypes threaten the efficacy of first-line treatments. (Funded by the Bavarian State Ministry of Health, Care, and Prevention and others.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2311981?query=TOC

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Wednesday, June 4, 2025

The #hemagglutinin proteins of clades 1 and 2.3.4.4b #H5N1 #HPAI viruses exhibit comparable attachment patterns to #avian and #mammalian tissues

Abstract

The global spread of the A/goose/Guangdong/1/96-lineage H5N1 highly pathogenic avian influenza (HPAI) viruses is accompanied by an expanded host range and the establishment of sustained viral transmission among dairy cattle. To evaluate if the evolving H5N1 viruses have changed tissue tropism over time, we compared the binding patterns of recombinant hemagglutinin (HA) proteins derived from clade 1 (A/Vietnam/1203/04, H5VN) and circulating clade 2.3.4.4b viruses detected from a wild bird (A/Eurasian Teal/Hong Kong/AFCD-HKU-23-14009-01020/2023, H5HK) and dairy cattle (A/bovine/Ohio/B24OSU-439/2024, H5OH). The HA protein of A(H1N1)pdm09 virus was included for comparison. Using bio-layer interferometry, H1 protein preferentially bound to the 2,6-linked sialoside 6'SLNLN while H5 proteins preferentially bound to the 2,3-linked sialoside 3'SLN. H5OH showed higher binding affinity to 3'SLN than H5HK and H5VN. The attachment pattern of H1 and H5 proteins to the respiratory tissues of different species and dairy cattle mammary glands were evaluated. Compared to the H1 protein, H5 proteins showed stronger binding to the lung epithelial cells of cat, cattle, chicken, ferret, human, and pig, and the clade 2.3.4.4b H5 proteins exhibited increased binding to pig and cattle bronchial epithelial cells. All H5 proteins attached to the alveolar and cistern epithelial cells in mammary glands where α2,3-linked and α2,6-linked sialyl glycans were detected by Maackia amurensis lectin II and Sambucus Nigra Lectin, respectively. Taken together, the HA proteins of clade 1 and 2.3.4.4b H5N1 viruses generally share comparable attachment patterns to avian and mammalian tissues, despite of evolving into antigenically distinct clades over the past 3 decades.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.06.02.657404v1

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#SARS-CoV-2 infection #enhancement by #amphotericin B: implications for disease management

ABSTRACT

Severe coronavirus disease 2019 (COVID-19) patients who require hospitalization are at high risk of invasive pulmonary mucormycosis. Amphotericin B (AmB), which is the first-line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, nystatin, natamycin, fluconazole, and caspofungin on SARS-CoV-2 infection and replication in vitro. Results showed that AmB and nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3, and Huh7 cells. At optimal concentrations, AmB and nystatin increase SARS-CoV-2 replication by up to 100- and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals tested had no impact on SARS-CoV-2 infection in vitro. Drug kinetic studies indicate that AmB enhances SARS-CoV-2 infection by promoting viral entry into cells. Additionally, knockdown of genes encoding for interferon-induced transmembrane (IFITM) proteins 1, 2, and 3 suggests AmB enhances SARS-CoV-2 cell entry by overcoming the antiviral effect of the IFITM3 protein. This study further elucidates the role of IFITM3 in viral entry and highlights the potential dangers of treating COVID-19 patients, with invasive pulmonary mucormycosis, using AmB.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00519-25?af=R

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Quantifying the #zoonotic #risk profile of European #influenza A viruses in #swine from 2010 to 2020 inclusive

ABSTRACT

H1 and H3 influenza A viruses (IAVs) circulating in European pigs are markedly distinct from those circulating in other global swine populations. These viruses exhibit significant genetic diversity, further expanded by periodic interspecies transmission of IAVs from humans into pigs, followed by sustained circulation. Several zoonotic IAV infections in humans in Europe have been associated with the 1C lineage of H1 IAVs. Given the predominance of H1 detections in pigs and their zoonotic potential, we quantified antigenic evolution of H1 viruses in European pigs using ferret and pig models and assessed diversity relative to swine IAV vaccine strains. Ferret and swine antisera comparisons revealed no significant differences in antibody responses. Viruses of the 1A.3.3.2 clade exhibited reduced cross-reactivity to human seasonal vaccine strains from 2009. Viruses of the 1B.1.2.2 clade showed no cross-reactivity to the 1978 human seasonal influenza viruses nor to candidate vaccine viruses (CVVs). Clades 1C.2.1 and 1C.2.2 human variant strains had variable cross-reactivity to the tested 1C lineage CVVs, and 1C.2.4 and 1C.2.5 clade viruses exhibited rapid genetic diversification. Many viruses tested were antigenically distant from swine influenza vaccine-representative strains, highlighting the need for updated vaccine formulations. Importantly, age-stratified human serum panels revealed limited population cross-protection to tested viruses, particularly for antigenically heterogenous viruses. These findings quantify the genetic and antigenic diversity of co-circulating IAV lineages and identify specific groups of viruses that may represent a greater risk to animal and public health. These results can be used to inform future pre-pandemic preparedness efforts.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00306-25?af=R

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

ABSTRACT

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

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00389-25?af=R

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#Phage-induced #protection against lethal #bacterial #reinfection

Significance

In 2021, antimicrobial-resistant bacteria were responsible for 1.14 million deaths and associated with 4.71 million deaths globally. Patients who experience sepsis often face a higher risk of reinfections and hospital readmissions. To combat this crisis, bacteriophages—viruses that infect and kill bacteria—are regaining interest as a potential solution. Here, we show that mice infected with extraintestinal pathogenic Escherichia coli and treated with phage HP3 not only recover from the initial infection but also gain protection against a secondary challenge with the same bacterial strain. The protective effect is dependent on the bacteriolytic action of the phage. These findings shift phages from being solely therapeutic antimicrobials to dual-action immunotherapeutics capable of both clearing and preventing bacterial infections.


Abstract

Bacteriophages, or phages, are viruses that target and infect bacteria. Due to a worldwide rise in antimicrobial resistance (AMR), phages have been proposed as a promising alternative to antibiotics for the treatment of resistant bacterial infections. Up to this point in history, phage use in preclinical animal studies, clinical trials, and emergency-use compassionate care cases has centered around the original observation from 1915 showing phage as lytic agent, and thus a treatment that kills bacteria. Here, we describe an activity associated with phage therapy that extends beyond lytic activity that results in long-term protection against reinfection. This activity is potent, providing almost complete protection against a second lethal infection for animals treated with phage therapy. The activity also reduced infection burden an astounding billion-fold over the control. Reinfection protection requires phage lytic killing of its target bacterium but is independent of additional phage therapy. The effect is not driven by phage alone, lingering phage resistors, or a sublethal inoculum. In vitro phage-lysed bacteria provide partial protection, suggesting a combination of phage-induced lytic activity and immune stimulation by phage treatment is responsible for the effect. These observations imply certain phages may induce host adaptive responses following the lysis of the infecting bacteria. This work suggests phage therapy may contain a dual-action effect, an initial treatment efficacy followed by a long-term protection against reoccurring infection, a therapeutic-vaccination mechanism of action.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/abs/10.1073/pnas.2423286122?af=R

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#Neuroinvasive #Oropouche virus in a patient with #HIV from extra-Amazonian #Brazil

{Excerpt}

A novel reassortant Oropouche virus (OROV) lineage (with medium [M], large [L], and small [S] RNA segments: M1L2S2) has driven Brazil's largest and most geographically widespread OROV epidemic, expanding beyond the endemic Amazon basin to establish local transmission across multiple Brazilian states and other previously unaffected Latin American countries. The rapid spread of this lineage underscores its evolutionary potential and reinforces its significance as a public health threat.1 Similar to chikungunya and Zika viruses, expanding arboviruses can exhibit unexpected clinical and epidemiological shifts, including vertical transmissions, neuroinvasive effects, and potentially fatal outcomes.2–4 Although OROV typically causes self-limited febrile illness, accumulating clinical and experimental evidence suggests neurotropic potential.5 This Correspondence describes the first confirmed case of neuroinvasive OROV infection caused by the emergent M1L2S2 lineage in extra-Amazonian Brazil, highlighting a potential synergistic mechanism of CNS invasion facilitated by HIV-induced immune dysregulation.

(...)


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Persistence of #SARS-CoV-2 #Alpha #Variant in White-Tailed #Deer, #Ohio, USA

Abstract

Free-ranging white-tailed deer (WTD) are highly susceptible to the SARS-CoV-2 virus. Through an opportunistic sampling of WTD in northeast Ohio, USA, during January–March 2023, we identified 6 SARS-CoV-2 lineages from 36 sequences using the pangolin lineages tool, including the B.1.1.7 lineage (Alpha variant) and BQ.1.1, BQ.1.1.63, BQ.1.1.67, BQ.1.23, and XBB.1.5.35 lineages (Omicron variant). The Alpha variant, introduced by a single human-to-deer transmission event, was detected in 5 WTD in January 2023, more than 1 year after the most recent detection of the Alpha variant in humans in Ohio (August 2021). A genetically similar B.1.1.7 lineage virus from WTD in a nearby county in Pennsylvania was positioned with our Ohio deer transmission cluster, suggesting deer-to-deer transmission. The persistence of the Alpha variant in WTD in Ohio warrants continued surveillance to monitor if WTD can become a reservoir for displaced SARS-CoV-2 variants.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/7/24-1922_article

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#Risk #evaluation of newly emerging #flu viruses based on genomic #sequences and AI

Abstract

The recent resurgence of highly pathogenic avian influenza H5N1 viruses in North America and Europe has heightened global concerns regarding potential influenza pandemics. Despite significant progress in the surveillance and prevention of emerging influenza viruses, effective tools for rapid and accurate risk assessment remain limited. Here, we present FluRisk, an innovative computational framework that integrates viral genomic data with artificial intelligence (AI) to enable rapid and comprehensive risk evaluation of emerging influenza strains. FluRisk incorporates a curated database of over 1,000 experimentally validated molecular markers linked to key viral phenotypes, including mammalian adaptation, mammalian virulence, mammalian transmission, human receptor-binding preference, and antiviral drug resistance. Leveraging these markers, we developed three state-of-the-art machine learning models to predict human adaptation, mammalian virulence, and human receptor-binding potential, all of which demonstrated superior performance compared to traditional approaches such as BLAST, prior models, and baseline classifiers. In addition, a reference-based method was implemented to provide preliminary estimates of human transmissibility and resistance to six commonly used antiviral drugs. To facilitate broad accessibility and practical application, we developed a user-friendly web server that integrates both the molecular marker atlas and predictive tools for influenza virus phenotyping (available at: http://www.computationalbiology.cn/FluRisk/#/). This computational platform offers a valuable resource for the timely risk assessment of emerging influenza viruses and supports global influenza surveillance efforts.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.18.649608v2

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Tuesday, June 3, 2025

#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 23 April to 27 May 2025 (#WHO, June 3 '25)

 


New human cases{2}: 

-- From 23 April to 27 May 2025, based on reporting date, the detection of influenza A(H5N1) in three humans, the detection of influenza A(H9N2) virus in eight humans and the detection of influenza A(H10N3) in one human were reported officially. 

-- Circulation of influenza viruses with zoonotic potential in animals: 

- High pathogenicity avian influenza (HPAI) outbreaks in poultry and non-poultry animals continue to be reported to the World Organisation for Animal Health (WOAH).{3} 

- The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4} 

-- Risk assessment{5}: 

- Sustained human to human transmission has not been reported in these events. Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not changed and remains low. 

- The occurrence of sustained human-to-human transmission of the viruses characterized so far from these events is currently considered unlikely

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

-- IHR compliance

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

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

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


Avian influenza viruses in humans 

Current situation:  

Since the last risk assessment of 22 April 2025, laboratory-confirmed human cases of A(H5N1) infection were reported to WHO from Bangladesh and China. 

-- A(H5N1), Bangladesh 

A human infection with an H5 clade 2.3.2.1a A(H5N1) virus was detected in a sample collected from a child in Khulna Division in April 2025, who recovered from his illness. Genetic sequence data are available in GISAID (E EPI_ISL_19875512; submission date 18 May 2025; Institute of Epidemiology, Disease Control & Research (IEDCR); Virology - National Influenza Centre (NIC)). 

WHO was notified of this case on 4 May 2025. In March 2025, an avian influenza A(H5N1) outbreak was reported in poultry in the same district (Jessore) where the case resides.{7} 

A second human infection with an H5 clade 2.3.2.1a A(H5N1) virus was retrospectively detected in a sample collected from a child in Khulna Division in February 2025, who recovered from his illness, according to genetic sequence data available in GISAID (EPI_ISL_19882255;  submission date 26 May 2025; Institute of Epidemiology, Disease Control & Research (IEDCR); Virology - National Influenza Centre (NIC)). WHO was notified of this case on 27 May 2025. 

-- A(H5N1), China 

On 10 May 2025, China notified WHO of one confirmed case of human infection with an avian influenza A(H5N1) virus in an adult traveling from Viet Nam that was detected through routine screening at the port of entry in China

The case was admitted to hospital in China on 7 April and had recovered at the time of notification. 

The likely source of exposure was domestic poultry at the case’s home. 

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

Infections in non-human mammals are also reported, including in marine and terrestrial mammals.{8} 

A list of bird and mammalian species affected by HPAI A(H5) viruses is maintained by FAO.{9}


Risk Assessment for avian influenza A(H5) viruses:  

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

- Most human cases so far have been documented as infections in people exposed to A(H5) viruses, for example, through contact with infected poultry or contaminated environments, including live poultry markets, and occasionally infected mammals and contaminated environments. 

- While the viruses continue to be detected in animals and related environments humans are exposed to, further human cases associated with such exposures are expected but unusual. 

- The impact for public health if additional cases are detected is minimal

- The current overall global public health risk of additional human cases is low

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

- No sustained human-to-human transmission has been identified associated with the recent reported human infections with avian influenza A(H5). 

- There has been no reported human-to-human transmission of A(H5N1) viruses since 2007, although there may be gaps in investigations. 

- In 2007 and the years prior, small clusters{10} of A(H5) virus infections in humans were reported, including some involving health care workers, where limited human-to-human transmission could not be excluded; however, sustained human-to-human transmission was not reported.  

- Available evidence suggests that the currently circulating influenza A(H5) viruses have not acquired the ability to efficiently transmit between people, therefore the likelihood of sustained human-tohuman transmission is thus currently considered unlikely at this time.  

-- 3. What is the likelihood of international spread of avian influenza A(H5) viruses by travellers?  

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


-- A(H9N2), China 

- Since the last risk assessment of 22 April 2025, eight human cases of infection with A(H9N2) influenza viruses were notified to WHO from China on 10 May 2025. 

- The cases were detected in Guizhou (two), Hunan (four) and Yunnan (one) provinces and Chongqing municipality (one). 

- Seven cases were in children

- All cases had symptom onset in April 2025. 

- One of the cases (a child) was hospitalized with pneumonia and a respiratory syncytial virus infection at the time of detection but had recovered at the time of reporting. 

- The other cases involved mild illnesses, were detected through the influenza-like illness (ILI) surveillance system, and the cases have recovered. 

- All cases but one had a known history of exposure to poultry prior to the onset of symptoms. 

- In all but one of the cases with known poultry exposure, environmental samples collected from areas associated with the cases tested positive for influenza A(H9) virus. 

- No further cases were detected among contacts of these cases and there was no epidemiological link between the cases.  


Risk Assessment for avian influenza A(H9N2):  

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

- Most human cases follow exposure to the A(H9N2) virus through contact with infected poultry or contaminated environments. 

- Most human infections of A(H9N2) to date have resulted in mild clinical illness. 

- Nearly 130 human infections with A(H9N2) cases have been reported to date since 2003, and six of these have been severe or fatal and three of these were known to have underlying medical conditions. 

- Since the virus is endemic in poultry in multiple countries in Africa and Asia{11}, further human cases associated with exposure to infected poultry are expected but remain unusual. 

- The impact to public health if additional cases are detected is minimal. 

- The overall global public health risk of additional human cases is low. 


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

- At the present time, no sustained human-to-human transmission has been identified associated with the event described above. 

- Current evidence suggests that influenza A(H9N2) viruses from these cases have not acquired the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely.  


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

- Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 

- If this were to occur, further community level spread is considered unlikely as current evidence suggests the A(H9N2) virus subtype has not acquired the ability to transmit easily among humans.  


-- A(H10N3), China 

- On 10 May 2025, China notified WHO of one confirmed case of human infection with avian influenza A(H10N3) virus in an adult from Shaanxi province. 

- The case developed symptoms on 13 April 2025, was admitted to hospital on 18 April with pneumonia and was improving at the time of notification. 

- According to the notification, the case had exposure to backyard poultry

- No additional cases have been reported among family members. 

- Environmental samples collected from the backyard tested negative for influenza A(H10) virus. 


Risk Assessment for avian influenza A(H10N3):  

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

- Human infections with avian influenza A(H10) viruses have been detected and reported previously.  

- The circulation and epidemiology of these viruses in birds have been previously reported.{12} 

- Avian influenza A(H10N3) viruses with different genetic characteristics have been detected previously in wild birds since the 1970s and more recently spilled over to poultry in some countries. 

- As long as the virus continues to circulate in birds, further human cases can be expected but remain unusual. 

- The impact to public health if additional sporadic cases are detected is minimal. 

- The overall global public health risk of additional sporadic human cases is low.   


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

- No sustained human-to-human transmission has been identified associated with the event described  above or past events with human cases of influenza A(H10N3) viruses. 

- Current epidemiologic and virologic evidence suggests that contemporary influenza A(H10N3) viruses assessed by the Global Influenza Surveillance and response System (GISRS) have not acquired the ability of sustained transmission among humans, therefore sustained human-to-human transmission is thus currently considered unlikely.   


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

- Should infected individuals from affected areas travel internationally, their infection may be  detected in another country during travel or after arrival. 

- If this were to occur, further community  level spread is considered unlikely based on current limited evidence. 


Overall risk management recommendations

Surveillance and investigations 

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

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

Countries should increase avian influenza surveillance in domestic and wild birds, enhance surveillance for early detection in cattle populations in countries where HPAI is known to be circulating, include HPAI as a differential diagnosis in non-avian species, including cattle and other livestock populations, with high risk of exposure to HPAI viruses; monitor and investigate cases in non-avian species, including livestock, report cases of HPAI in all animal species, including unusual hosts, to WOAH and other international organizations, share genetic sequences of avian influenza viruses in publicly available databases, implement preventive and early response measures to break the HPAI transmission cycle among animals through movement restrictions of infected livestock holdings and strict biosecurity measures in all holdings, employ good production and hygiene practices when handing animal products, and protect persons in contact with suspected/infected animals.{13}  

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

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


Notifying WHO 

All human infections caused by a new subtype of influenza virus are notifiable under the International Health Regulations (IHR, 2005).{14} State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed{15} case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic{16}. Evidence of illness is not required for this report. 

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


Virus sharing and risk assessment 

It is critical that these influenza viruses from animals or from people are fully characterized in appropriate animal or human health influenza reference laboratories. Under WHO’s Pandemic Influenza Preparedness (PIP) Framework, Member States are expected to share influenza viruses with pandemic potential on a timely basis{17} with a WHO Collaborating Centre for influenza of GISRS. The viruses are used by the public health laboratories to assess the risk of pandemic influenza and to develop candidate vaccine viruses.  

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


Risk reduction 

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

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

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


Trade and travellers 

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

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


Links:  

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

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

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

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

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

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

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

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

OFFLU http://www.offlu.org/

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

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

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

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

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

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

{7} WOAH. WAHIS. Bangladesh - High pathogenicity avian influenza viruses (poultry) (Inf. with). Event 6351. Available at: https://wahis.woah.org/#/in-event/6351/dashboard

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

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

{10} A cluster is defined as two or more persons with onset of symptoms within the same 14-day period and who are associated with a specific setting, such as a classroom, workplace, household, extended family, hospital, other residential institution, military barracks or recreational camp. 

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

{12} Wang X, Yu H, Ma Y, Zhang P, Wang X, Liang J et al. 2025. The novel H10N3 avian influenza virus acquired airborne transmission among chickens: an increasing threat to public health. [Pre-print] mBio 16:e02363-24. https://doi.org/10.1128/mbio.02363-24

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

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

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

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

{17} World Health Organization. Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework (2017). Available at: https://apps.who.int/iris/handle/10665/259402

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Source: World Health Organization, https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--27-may-2025

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Single-Cell #Analysis of Host Responses in #Bovine #Milk Somatic Cells (bMSCs) Following #HPAIV Bovine #H5N1 #Influenza Exposure

Abstract

The 2024 outbreak of highly pathogenic avian influenza virus (HPAIV) H5N1 in U.S. dairy cattle presented an unprecedented scenario where the virus infected bovine mammary glands and was detected in milk, raising serious concerns for public health and the dairy industry. Unlike previously described subclinical influenza A virus (IAV) infections in cattle, H5N1 infection induced severe clinical symptoms, including respiratory distress, mastitis, and abnormal milk production. To understand the host immune responses and changes, particularly in the mammary gland, we performed single-cell RNA sequencing analysis on bovine milk somatic cells (bMSCs) in vitro exposed to an H5N1 isolate from an infected dairy farm. We identified ten distinct cell clusters and observed a shift toward type-2 immune responses, characterized by T cells expressing IL13 and GATA3, and three different subtypes of epithelial cells based on the expression of genes associated with milk production. Our study revealed temporal dynamics in cytokine expression, with a rapid decline in luminal epithelial cells and an increase in macrophages and dendritic cells, suggesting a role in increased antigen presentation. While viral RNA was detected in bulk-exposed bMSC samples via qRT-PCR, no viral reads were observed in the scRNA-seq data, indicating that the immune responses captured may be due to exposure to viral components rather than productive infection. This research fills a critical gap in understanding the immune responses of bovine mammary glands to H5N1 exposure and highlights the need for further investigation into therapeutic strategies for managing such outbreaks.

Source: Viruses, https://www.mdpi.com/1999-4915/17/6/811

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Monday, June 2, 2025

Recurrent #MERS-CoV #Transmission in #Saudi Arabia– Renewed Lessons in #Healthcare #Preparedness and Surveillance

{Excerpt}

The World Health Organization (WHO) had recently announced on May 12, 2025, the reporting of nine new laboratory-confirmed cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Saudi Arabia [1]. This announcement is a sobering reminder that while the global community remains focused on emergent threats like avian influenza or post-pandemic resilience, endemic zoonotic diseases like MERS-CoV may continue to circulate, evolve, and exploit gaps in infection prevention.

(...)

Source: Journal of Epidemiology and Global Health, https://link.springer.com/article/10.1007/s44197-025-00426-6

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

The samples collected in two (2) wild bird species: Red Shank (Tringa totanus) and Arctic Warbler (Phylloscopus borealis), that tested positive for Notifiable Avian Influenza Subtype H5N1 were part of the regular wildlife disease surveillance activity being conducted by the wetland park. In response, additional samples were collected from wild birds, and all tested negative for Avian Influenza. Comprehensive surveillance and sample collection efforts in the surrounding domestic poultry population also confirmed no presence of Avian Influenza.

Source: WOAH, https://wahis.woah.org/#/in-review/6523

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

HPAI H5N1 confirmed in backyard poultry farm with approx. 190 birds (laying hens). Susupicion date 27/05/2025 - some birds with neurological signs, one dead. Laboratory diagnosis confirmed at the Latvian National Reference Laboratory for avian influenza.

Source: WOAH, https://wahis.woah.org/#/in-review/6528

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Sunday, June 1, 2025

The Jabach Altarpiece, Albrecht Durer (1504)

 


Public Domain.

Source: WikiArt, https://www.wikiart.org/en/albrecht-durer/the-jabach-altarpiece-1504

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