#Influenza #H1N1pdm09 Virus with Reduced Susceptibility to #Baloxavir, #Japan, 2024

Abstract

Influenza A(H1N1)pdm09 virus carrying an I38N substitution was detected in an untreated teenager in Japan. The I38N mutant virus exhibited reduced susceptibility to baloxavir but remained susceptible to neuraminidase inhibitors and showed reduced growth capability. Monitoring antiviral drug susceptibility of influenza viruses is necessary to aid public health planning and clinical recommendations.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1123_article

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#Outbreak of #Marburg Virus Disease, Equatorial Guinea, 2023

Abstract

In February 2023, the government of Equatorial Guinea declared an outbreak of Marburg virus disease. We describe the response structure and epidemiologic characteristics, including case-patient demographics, clinical manifestations, risk factors, and the serial interval and timing of symptom onset, treatment seeking, and recovery or death. We identified 16 laboratory-confirmed and 23 probable cases of Marburg virus disease in 5 districts and noted several unlinked chains of transmission and a case-fatality ratio of 90% (35/39 cases). Transmission was concentrated in family clusters and healthcare settings. The median serial interval was 18.5 days; most transmission occurred during late-stage disease. Rapid isolation of symptomatic case-patients is critical in preventing transmission and improving patient outcomes; community engagement and surveillance strengthening should be prioritized in emerging outbreaks. Further analysis of this outbreak and a One Health surveillance approach can help prevent and prepare for future potential spillover events.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/5/24-1749_article

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#Genomic #signatures and #host #adaptation of #H5N1 clade 2.3.4.4b: A call for global #surveillance and multi-target antiviral strategies

Highlights

• Phylogenetic analysis of genotype B3.13 and D1.1 across the species.

• Mutations on the receptor binding sites related to receptor preferring.

• Host adaptability differences between B3.13 and D1.1.

• Antivirals resistance mutations emergence of genotype B3.13 and D1.1.

Abstract

The recent report of the first fatality associated with infection by influenza virus H5N1 clade 2.3.4.4b, identified as genotype D1.1, which is distinct from the B3.13 genotype, has sparked fears of a potential human pandemic. However, the genetic relationships between B3.13 and D1.1, as well as their origins, host adaptability, and antiviral resistance, remain poorly understood. Here we conducted a comprehensive phylogenetic and comparative analysis of H5N1 clade 2.3.4.4b across multiple species, in order to identify the molecular characteristics and frequency of resistance mutations in these two genotypes, elucidate their evolutionary trajectories, and assess their implications for public health. Our results demonstrate that B3.13 exhibits mammalian adaptability, while D1.1 retains avian adaptability. Importantly, both genotypes display limited occurrences of human-like signatures, which can help alleviate public anxiety. Additionally, the emergence of the resistance mutations in the clade 2.3.4.4b on the binding sites of antivirals calls for the development of multi-target antiviral strategies to mitigate the risk of resistant strain reassortment.

Source: Current Research in Microbiological Sciences, https://www.sciencedirect.com/science/article/pii/S2666517425000392?via%3Dihub

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A #Wildlife #Health #Outbreak #Response Table-top Exercise for #Pandemic Preparedness #Planning

Abstract

Zoonotic diseases have received significantly more attention over the last few decades, emerging with increasing frequency and causing the majority of notable disease outbreaks in this century, including the COVID-19 pandemic. As human activities and shifting climate patterns induce changes in the environment that alter habitat and range of reservoir species, the potential for human and animal interactions will increase and enhance the opportunity for spillover. Thus, any emergency response preparedness planning must take into account the function and coordination of agencies across the sectors of human, animal and environmental health. Within the Commonwealth of Pennsylvania a table-top exercise was performed to evaluate a multi-agency response during a hypothetical zoonotic disease investigation. The exercise was evaluated by the participants to gain feedback on the overall process and lessons learned. Here, we describe the tabletop exercise scenario and the insights gained. We found that differences in operational structure create challenges for interdepartmental communication and in the ability to resource a coordinated response, highlighting opportunities to develop infrastructure that will facilitate future actions. A set of recommendations are outlined that may enhance cross-agency activities and promote more effective and efficient emergency response.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.01.646690v1

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

One red fox in Sachsen and one in Nordrhein-Westfalen States.

Source: WOAH, https://wahis.woah.org/#/in-review/6398

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#NASA #Update on the #Size Estimate and #Lunar #Impact Probability of #Asteroid 2024 #YR4

Since near-Earth asteroid 2024 YR4 was first discovered in December 2024, NASA and the worldwide planetary defense community have continued to observe the asteroid, which was ruled out as a significant impact risk to Earth. New infrared observations from NASA’s James Webb Space Telescope have decreased the uncertainty of the asteroid’s size and 2024 YR4 is now estimated to be 174-220 feet (53-67 meters), about the size of a 10-story building. The previous size estimate of 131-295 feet (40-90 meters) was derived from visible light measurements from ground-based telescopes.  

(...)

Experts at NASA’s Center for Near Earth Object Studies at the agency’s Jet Propulsion Laboratory have updated 2024 YR4’s chance of impacting the Moon on Dec. 22, 2032 from 1.7% as of late February to 3.8% based on the Webb data and observations from ground-based telescopes. There is still a 96.2% chance that the asteroid will miss the Moon. In the small chance that the asteroid were to impact, it would not alter the Moon’s orbit.  

After mid-April, asteroid 2024 YR4 will be too far and faint to be observed by ground-based telescopes but Webb will observe the asteroid again in May.  

Source: NASA, https://science.nasa.gov/blogs/planetary-defense/2025/04/02/nasa-update-on-the-size-estimate-and-lunar-impact-probability-of-asteroid-2024-yr4/

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#India, Andhra Pradesh reports first #human #death owing to #H5N1 virus

{Excerpt}

(...) Samples of a two-year-old girl from Palnadu district’s Narasaraopeta, who died of multi-organ failure at AIIMS-Mangalagiri on March 16, tested positive for H5N1 virus. The confirmation from National Institute of Virology (NIV-Pune) came on March 31. (...)

Source: The Hindu, https://www.thehindu.com/news/national/andhra-pradesh/ap-reports-first-human-death-owing-to-h5n1-virus/article69403347.ece

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#Clinical presentation of #Oropouche virus #infection: A systematic review and meta-analysis

Abstract

Background

The recent surge in incidence and geographic spread of OROV infections poses an escalating threat to global public health. However, studies exploring the clinical signs of OROV infection remains exceedingly limited.

Methods

We searched for OROV studies published until June 17, 2024, in several electronic databases including MEDLINE, EMBASE, SCOPUS, and the Cochrane Library.

Results

In total, 15 studies involving 806 patients with OROV infection were eligible for inclusion. General symptoms with fever and headache were the most common. Gastrointestinal disturbances like nausea/vomiting, anorexia, and odynophagia were also prevalent, along with ocular symptoms, mainly retro-orbital pain, photophobia, and redness. Respiratory symptoms, such as cough, sore throat and nasal congestion, are present, and skin-related issues like rash, pruritus, and pallor were also identified.

Conclusion

Overall, this study provides a foundational understanding of OROV’s clinical manifestations to guide diagnosis, management, and public health interventions against this neglected tropical disease.

Author summary

In the realm of life sciences, understanding the full scope of infectious diseases is crucial for protecting public health. Oropouche virus (OROV), a relatively under-studied pathogen, has been showing an alarming increase in both incidence and geographical spread recently. Despite its growing threat, our knowledge of the clinical symptoms it causes has been severely lacking. Our study is the first of its kind to comprehensively review and analyze available research on OROV-related symptoms. By pooling 15 studies involving 806 patients, we’ve uncovered a range of symptoms from common fever and headache to less-known ocular, gastrointestinal, and skin - related issues. This new understanding is vital. For scientists, it lays the groundwork for further research into OROV’s biology and disease mechanisms. For non-scientists, it helps in early recognition of the disease, which is key to getting proper medical care and preventing its spread.

Source: PLoS Neglected Tropical Diseases, https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012962

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Rates of #infection with other #pathogens after a positive #COVID19 test versus a negative test in #US #veterans (November, 2021, to December, 2023): a retrospective cohort study

Summary

Background

SARS-CoV-2 infection leads to post-acute sequelae that can affect nearly every organ system, including the immune system. However, whether an infection with SARS-CoV-2 is associated with increased risk of future infections with other pathogens is not yet fully characterised. In this study, we aimed to test the association between a positive test for COVID-19, compared with a negative test, and rates of future infections with other pathogens.

Methods

We used the US Department of Veterans Affairs health-care databases to build a spatiotemporally aligned cohort of 231 899 people with a positive COVID-19 test and 605 014 with a negative COVID-19 test (test-negative control group) between Nov 1, 2021, and Dec 31, 2023. We first did a discovery approach to map the associations between those with a positive COVID-19 test versus a negative test and laboratory-based outcomes of infectious illnesses. We then compared rates of a prespecified set of infectious disease outcomes between those with and without a positive COVID-19 test. To evaluate the specificity of the findings to COVID-19, we compared the rates of a prespecified set of infectious disease outcomes in a spatiotemporally aligned cohort of people admitted to hospital for COVID-19 (n=12 450) versus those admitted for seasonal influenza (n=3293). Outcomes were ascertained 30 days after the date of the first test until the end of follow-up (365 days after the first test plus 30 days, death, or July 18, 2024, whichever came first). An inverse probability weighting approach was used to balance demographic and health characteristics across cohorts. Log-binomial regression models were used to estimate risk ratios (RRs) and 95% CIs.

Findings

In the 12 months of follow-up, compared with participants who had a negative test for COVID-19, people with COVID-19 who did not require admission to hospital during the acute phase of infection had increased test positivity rates for bacterial infections (in blood, urine, and respiratory cultures) and viral diseases (including Epstein–Barr virus, herpes simplex virus reactivation, and respiratory viral infections). People who were positive for COVID-19 and admitted to hospital also had increased rates of bacterial infections in blood, respiratory, and urine biospecimens, and viral infections in blood and respiratory biospecimens. Analyses of prespecified outcomes showed that, compared with the test-negative control group, participants with a positive COVID-19 test who were not admitted to hospital had significantly increased rates of outpatient diagnosis of infectious illnesses (RR 1·17 [95% CI 1·15–1·19]), including bacterial, fungal, and viral infections; outpatient respiratory infections (1·46 [1·43–1·50]); and admission to hospital for infectious illnesses (1·41 [1·37–1·45]), including for sepsis and respiratory infections; the rates of prespecified outcomes were generally higher among those who were admitted to hospital for COVID-19 during the acute phase. Compared with people admitted to hospital for seasonal influenza, those admitted for COVID-19 had higher rates of admission to hospital for infectious illnesses (1·24 [1·10–1·40]), admission to hospital for sepsis (RR 1·35 [1·11–1·63]), and in-hospital use of antimicrobials (1·23 [1·10–1·37]).

Interpretation

Our results suggest that a positive test for COVID-19 (vs a negative test) was associated with increased rates of diagnosis of various infections in the 12 months following an acute SARS-CoV-2 infection. The putative long-term effects of COVID-19 on the immune system and the propensity for infection with other pathogens should be further evaluated in future studies.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00831-4/abstract?rss=yes

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Dairy #cattle #herds mount a characteristic #antibody response to highly pathogenic #H5N1 avian #influenza viruses

Abstract

An unprecedented outbreak of a highly pathogenic avian influenza virus, H5 clade 2.3.4.4b, was reported in United States dairy cattle during the spring of 2024. It has now spread to hundreds of herds across multiple states. In humans, antibodies to the hemagglutinin (HA) protein confer the strongest protection against infection. Human herd immunity limits viral spread but also drives the emergence of antigenic variants that escape dominant antibody responses. We used store-bought milk to profile the collective H5N1 antibody response of dairy cattle herds. We detected HA binding antibodies in specific samples from states with recent/ongoing outbreaks. These antibodies present in milk neutralized replicating virus expressing dairy cattle HA and neuraminidase (NA). Despite originating from independent vendors, dairies/plants, geographic regions, and time, antibodies present in these samples are remarkably similar in activity and HA binding specificity. The dominant antibody response was clade 2.3.4.4b HA specific, followed by cross-reactivity with other H5s. Whether the uniformity of the response is a pathway to achieve herd immunity or an avenue for antigenic variants to rapidly escape remains to be seen.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.04.01.646587v1

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Highly pathogenic avian #influenza #management in high-density #poultry #farming areas

Abstract

The continuous spread of highly pathogenic avian influenza H5 viruses poses significant challenges, particularly in regions with high poultry farm densities where conventional control measures are less effective. Using phylogeographic and phylodynamic tools, we analysed virus spread in Southwestern France in 2020-21, a region with recurrent outbreaks. Following a single introduction, the virus spread regionally, mostly affecting duck farms, peaking in mid-December with a velocity of 27.8 km/week and an effective reproduction number between farms (Re) of 3.8, suggesting the virus can spread beyond current control radii. Transmission declined after late December following preventive culling. Farm infectiousness was estimated around 9 days. Duck farm density was the main driver of virus spread and we identified farm density and proximity thresholds required to maintain effective control (Re < 1). These findings offer actionable guidance to support regional biosecurity and to improve the robustness of the poultry sector to mitigate future outbreaks.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.25.645233v1

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Intranasal #influenza virus-vectored #vaccine offers protection against clade 2.3.4.4b #H5N1 #infection in small animal #models

Abstract

The highly pathogenic avian influenza (HPAI) H5N1 virus has been endemic in aquatic birds since 1997, causing outbreaks in domestic poultry and occasional human infections worldwide. Recently, the cross-species transmission of a new reassortant variant from clade 2.3.4.4b of H5N1 to cattle in the US has heightened concerns regarding the expansion of host range and potential human infection. As eradicating the H5N1 virus from its reservoir is impossible, it is essential to prepare for a potential pandemic caused by an H5N1 derivative. Utilizing a deleted-NS1 live attenuated influenza viral vector vaccine system (DelNS1 LAIV), a system we have previously used in the development of a COVID-19 vaccine, we have rapidly developed an intranasal vaccine for cattle H5N1 and related clade 2.3.4.4b strains, based on publicly available sequences. Our research demonstrates that a single intranasal immunization can provide effective protection against lethal challenges from HPAI cattle or mink H5N1 variants, offering strong, sustained immunity after two months in female mouse and male hamster models. Immunogenicity analysis reveals that intranasal vaccination with DelNS1 LAIV induces robust neutralizing antibody, mucosal IgA and T cell responses in mice. It is crucial to further evaluate the DelNS1-H5N1 LAIV system to prepare for potential future H5N1 outbreaks in humans.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-58504-z

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

On 31 March 2025 a clinical suspicion was reported to the Danish Veterinary and Food Administration. The affected poultry holding consists of 24 hens. On 1 April 2025 highly pathogenic avian influenza subtype H5N1 was confirmed by the national reference laboratory. A 3 km protection zone and a 10 km surveillance zone has been established. The culling was completed on 1 April 2025. Carcasses will be disposed of by rendering.

Source: WOAH, https://wahis.woah.org/#/in-review/6392

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

 Death was observed in Guinea Fowl in Jharkhand State.

Source: WOAH, https://wahis.woah.org/#/in-review/6376

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

House Crows in Bihar State.

Source: WOAH, https://wahis.woah.org/#/in-review/6391

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#PA and #PAX: two key #proteins from segment 3 of the #influenza viruses

Abstract

In recent years, the influenza viruses have posed an increasingly severe threat to public health. It is essential to analyze the virulence and pathogenesis of influenza viruses to prevent and control them, as well as create antiviral drugs. Previous studies have revealed that influenza virus segment 3 codes for not only the PA protein but also a novel protein, PA-X. PA protein is one subunit of the polymerase of influenza viruses and plays a critical role in its life cycle. PA presented endonuclease activity, the transcription and replication of the viral genome, viral virulence, protein degradation, and host immune response by interacting with viral proteins, including PB2, PB1, and host factors, including ANP32A, CHD6, HAX1, hCLE, HDAC6, MCM complex. PA mutations were involved in the viral replication, pathogenicity, and transmission of influenza viruses in poultry, mammals, and humans. PA-X is an open reading frame generated by +1 ribosomal code shift at the N-terminal amino acids of segment 3 and possesses the shutoff activity of host gene expression, regulating the host immune response, viral virulence and transmission. Therefore, PA is one ideal target for the development of antiviral drugs against influenza viruses. Baloxavir marboxil (BXM) and Favipiravir are two very effective anti-influenza virus drugs targeting the PA endonuclease domain of influenza A viruses. In this review, we summarized the structures, viral replication, virulent determinants and transmission, host factors, innate immunity, and antiviral drugs involved in PA and PA-X. The information is of great value for underlying the mechanism of viral replication and developing novel effective strategies to prevent and control influenza infection and the pandemic.

Source: Frontiers in Cellucal and Infection Microbiology, https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1560250/full

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Introducing a #framework for within-host #dynamics and #mutations modelling of #H5N1 #influenza infection in #humans

Abstract

Avian influenza A(H5N1) poses a public health risk due to its pandemic potential should the virus mutate to become human-to-human transmissible. To date, reported influenza A(H5N1) human cases have typically occurred in the lower respiratory tract with a high case fatality rate. There is prior evidence of some influenza A(H5N1) strains being a small number of amino acid mutations away from achieving droplet transmissibility, possibly allowing them to be spread between humans. We present a mechanistic within-host influenza A(H5N1) infection model, novel for its explicit consideration of the biological differences between the upper and lower respiratory tracts. We then estimate a distribution of viral lifespans and effective replication rates in human H5N1 influenza cases. By combining our within-host model with a viral mutation model, we determine the probability of an infected individual generating a droplet transmissible strain of influenza A(H5N1) through mutation. For three mutations, we found a peak probability of approximately 10(^-3) that a human case of H5N1 influenza produces at least one virion during the infectious period. Our findings provide insights into the risk of differing infectious pathways of influenza A(H5N1) (namely avian-human vs avian-mammal-human routes), demonstrating the three-mutation pathway being a cause of concern in human cases.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.09.01.24312235v3

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#Population #Immunity to #HA Head, Stalk and #NA of HP Avian #Influenza 2.3.4.4b A(#H5N1) viruses in #USA and Impact of Seasonal Influenza on A(H5N1) Immunity

Abstract

The unprecedented 2.3.4.4b A(H5N1) outbreak in dairy cattle, poultry, and spillover to humans in the United States (US) poses a major public health threat. Population immunity is a critical component of influenza pandemic risk assessment. We conducted a comprehensive assessment of the population immunity to 2.3.4.4b A(H5N1) viruses and analyzed 1794 sera from 723 people (0.5-88 yrs) in multiple US geographic regions during 2021-2024. Low pre-existing neutralizing and hemagglutinin (HA) head binding antibodies and substantial cross reactive binding antibodies to N1 neuraminidase (NA) of 2.3.4.4b A(H5N1) were detected in US population. Antibodies to group 1 HA stalk were also prevalent with an age-related pattern. A(H1N1)pdm09 infection and influenza vaccination did not induce neutralizing antibodies but induced significant rise of NA inhibition (NAI) antibodies to N1 of 2.3.4.4b A(H5N1), and group 1 HA stalk antibodies. Understanding population susceptibility to novel influenza is essential for pandemic preparedness.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.03.30.25323419v1

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

 A poultry farm in Sachsen-Anhalt Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6378

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

Backyard and Farmed Poultry in Karnataka State.

Source: WOAH, https://wahis.woah.org/#/in-review/6366

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