Saturday, April 5, 2025

Impact of inactivated #vaccine on #transmission and #evolution of #H9N2 avian #influenza virus in #chickens

Abstract

H9N2 avian influenza virus (AIV) is endemic in poultry worldwide and increasingly zoonotic. Despite the long-term widespread use of inactivated vaccines, H9N2 AIVs remain dominant in chicken flocks. We demonstrated that inactivated vaccines did not prevent the replication of H9N2 AIVs in the upper airway of vaccinated chickens. Viral transmission was enhanced during sequential passage in vaccinated chickens, which was attributed to the restricted production of defective interfering particles and the introduction of stable mutations (NP-N417D, M1-V219I, and NS1-R140W) which enhanced viral replication. Notably, the genetic diversity of H9N2 AIVs was greater and included more potential mammal/human-adapted mutations after passage through vaccinated chickens than through naïve chickens, which might facilitate the emergence of mammal-adapted strains. By contrast, vaccines inducing cellular/mucosal immunity in the upper respiratory tract effectively limit H9N2 AIV. These findings highlight the limitations of inactivated vaccines and the need for revised vaccination strategies to control H9N2 AIV.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01115-y

____

#Coronavirus Disease Research #References (by AMEDEO, April 5 '25)

 


    Ann Intern Med

  1. DACSO CC
    Coadministration of RSV + influenza or COVID-19 vaccines was noninferior to separate administration for immune responses in adults aged >/=50 y.
    Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00904.
    PubMed         Abstract available

  2. AMAN M, Jeevananthan A, Martinez-Cruz M, Namasingh N, et al
    Endocrinology: What You May Have Missed in 2024.
    Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00990.
    PubMed         Abstract available

  3. HAMED HKA, Nachman A, Riopel N, Schuster M, et al
    Infectious Diseases: What You May Have Missed in 2024.
    Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00925.
    PubMed         Abstract available

  4. CORONADO GD, Petrik AF, Thompson JH, Leo MC, et al
    Patient Navigation to Improve Colonoscopy Completion After an Abnormal Stool Test Result : A Randomized Controlled Trial.
    Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-24-01885.
    PubMed         Abstract available


    Antiviral Res

  5. ZHU Y, Gao Z, Feng X, Hu Y, et al
    Comprehensive preclinical characterization of IPB29, a pan-coronavirus fusion inhibitor under clinical trials.
    Antiviral Res. 2025;237:106154.
    PubMed         Abstract available


    BMJ

  6. VANDERSLOTT S
    Confronting the shortcomings of covid-19 vaccination will help us in future pandemics.
    BMJ. 2025;388:r590.
    PubMed        


    Clin Infect Dis

  7. ADAMS K, Garg S, Tartof SY, Irving SA, et al
    Patterns in prescribing and dispensing of influenza antivirals among adults with influenza presenting to urgent care and emergency department settings, VISION Network, 2023-2024.
    Clin Infect Dis. 2025 Apr 4:ciaf178. doi: 10.1093.
    PubMed         Abstract available

  8. DORAIVELU K, Williams S, Hazell M, Smith S, et al
    The dynamic impact of community social vulnerability on COVID-19 outcomes: A census tract-level analysis of Fulton County, GA.
    Clin Infect Dis. 2025 Apr 3:ciaf177. doi: 10.1093.
    PubMed         Abstract available


    Int J Infect Dis

  9. FANG S, Zhu L, Bai S, Tian W, et al
    Year-round infectome profiling of acute febrile respiratory illness unveiled complex epidemiological dynamics post-lifting of COVID-19 restrictions.
    Int J Infect Dis. 2025 Mar 29:107896. doi: 10.1016/j.ijid.2025.107896.
    PubMed         Abstract available


    J Med Virol

  10. LAI C, Lu S, Yang Y, You X, et al
    Myeloid-Driven Immune Suppression Subverts Neutralizing Antibodies and T Cell Immunity in Severe COVID-19.
    J Med Virol. 2025;97:e70335.
    PubMed         Abstract available

  11. KUMAR R, Verma A, Kamboj H, Bhattacharya TK, et al
    H3K27-me3 Inhibition Induces YTHDF2-Mediated Decay of m6A-Marked Severe Acute Respiratory Syndrome Coronavirus 2 Transcripts.
    J Med Virol. 2025;97:e70332.
    PubMed         Abstract available

  12. REUS P, Torbica E, Rothenburger T, Bechtel M, et al
    Papaverine Targets STAT Signaling: A Dual-Action Therapy Option Against SARS-CoV-2.
    J Med Virol. 2025;97:e70319.
    PubMed         Abstract available


    J Virol

  13. XIAO X, Li S, Zheng Z, Ji Y, et al
    Targeting USP22 to promote K63-linked ubiquitination and degradation of SARS-CoV-2 nucleocapsid protein.
    J Virol. 2025 Apr 4:e0223424. doi: 10.1128/jvi.02234.
    PubMed         Abstract available

  14. GHIMIRE R, Shrestha R, Amaradhi R, Liu L, et al
    Toll-like receptor 7 (TLR7)-mediated antiviral response protects mice from lethal SARS-CoV-2 infection.
    J Virol. 2025 Mar 31:e0166824. doi: 10.1128/jvi.01668.
    PubMed         Abstract available


    Lancet

  15. GOSTIN LO, Friedman EA, Dhai A, Zia-Zarifi S, et al
    COVID-19: border closures violate human rights - Authors' reply.
    Lancet. 2025;405:1054.
    PubMed        

  16. SILVA DS, Razum O
    COVID-19: border closures violate human rights.
    Lancet. 2025;405:1053-1054.
    PubMed        


    MMWR Morb Mortal Wkly Rep

  17. JOBE NB, Rose E, Winn AK, Goldstein L, et al
    Human Metapneumovirus Seasonality and Co-Circulation with Respiratory Syncytial Virus - United States, 2014-2024.
    MMWR Morb Mortal Wkly Rep. 2025;74:182-187.
    PubMed         Abstract available


    Science

  18. COHEN J
    NIH cancels research grants for COVID-19 and future pandemics.
    Science. 2025;388:16.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, April 5 '25)

 


    Ann Intern Med

  1. DACSO CC
    Coadministration of RSV + influenza or COVID-19 vaccines was noninferior to separate administration for immune responses in adults aged >/=50 y.
    Ann Intern Med. 2025 Apr 1. doi: 10.7326/ANNALS-25-00904.
    PubMed         Abstract available


    Antimicrob Agents Chemother

  2. PANG Y, Li H, Chen X, Cao Y, et al
    A phase I, single-center, randomized, open-label, three-period crossover study to evaluate the drug-drug interaction between ZSP1273 and oseltamivir in healthy Chinese subjects.
    Antimicrob Agents Chemother. 2025;69:e0172924.
    PubMed         Abstract available

  3. ZHAO L, Li C, Wang M, Zhou M, et al
    Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier.
    Antimicrob Agents Chemother. 2025 Mar 10:e0155624. doi: 10.1128/aac.01556.
    PubMed         Abstract available


    Biochem Biophys Res Commun

  4. LIU HL, Lin S, Hung W, Chang DC, et al
    A novel replicase-mediated self-amplifying RNA amplification mechanism of the SARS-CoV-2 replication-transcription system.
    Biochem Biophys Res Commun. 2025;758:151654.
    PubMed         Abstract available


    Biochemistry

  5. E SANTO AA, Reis A, Pinheiro AA, da Costa PI, et al
    Design of Mimetic Antibodies Targeting the SARS-CoV-2 Spike Glycoprotein Based on the GB1 Domain: A Molecular Simulation and Experimental Study.
    Biochemistry. 2025;64:1541-1549.
    PubMed         Abstract available


    BMC Pediatr

  6. JAFARI N, Akbari H, Maghsoodi A, Sarbakhsh P, et al
    The attitude of the unvaccinated children's parents toward pediatric COVID-19 vaccination in Tabriz, Iran.
    BMC Pediatr. 2025;25:248.
    PubMed         Abstract available


    Epidemiol Infect

  7. MONGE S, Humphreys J, Nicolay N, Braeye T, et al
    Comparison of two methods for the estimation of COVID-19 vaccine effectiveness of the autumnal booster within the VEBIS-EHR network in 2022/23.
    Epidemiol Infect. 2025;153:e54.
    PubMed         Abstract available

  8. MIN KH, Kim JH, Gil JY, Park JH, et al
    Factors associated with carditis adverse events following SARS-COV-2-19 vaccination.
    Epidemiol Infect. 2025;153:e51.
    PubMed         Abstract available


    J Exp Med

  9. MADSEN A, Okba NMA, Pholcharee T, Matz HC, et al
    Identification of a seasonal influenza vaccine-induced broadly protective neuraminidase antibody.
    J Exp Med. 2025;222:e20241930.
    PubMed         Abstract available


    J Infect Dis

  10. FRUTOS AM, Tenforde MW, Sundaresan D, Naleway AL, et al
    Influenza-associated hospitalization rates by underlying conditions, 2016-17 to 2019-20: A retrospective cohort study.
    J Infect Dis. 2025 Mar 28:jiaf164. doi: 10.1093.
    PubMed         Abstract available


    J Virol

  11. XIAO X, Wang X, Xu F, Liang Y, et al
    Synergistic effects of PA (S184N) and PB2 (E627K) mutations on the increased pathogenicity of H3N2 canine influenza virus infections in mice and dogs.
    J Virol. 2025 Apr 4:e0198424. doi: 10.1128/jvi.01984.
    PubMed         Abstract available


    MMWR Morb Mortal Wkly Rep

  12. JOBE NB, Rose E, Winn AK, Goldstein L, et al
    Human Metapneumovirus Seasonality and Co-Circulation with Respiratory Syncytial Virus - United States, 2014-2024.
    MMWR Morb Mortal Wkly Rep. 2025;74:182-187.
    PubMed         Abstract available


    Pediatrics

  13. ROWE SL, Sullivan SG, Munoz FM, Coates MM, et al
    COVID-19 Vaccination During Pregnancy and Major Structural Birth Defects.
    Pediatrics. 2025 Mar 14:e2024069778. doi: 10.1542/peds.2024-069778.
    PubMed         Abstract available

  14. COLEY RL, Leer J, Lanteri L
    Trends in Mental and Behavioral Health Risks in Adolescents: 1999-2021.
    Pediatrics. 2025;155:e2024068774.
    PubMed         Abstract available

  15. DESILVA MB, Haapala J, Vazquez-Benitez G, Daley MF, et al
    COVID-19 and Completion of Select Routine Childhood Vaccinations.
    Pediatrics. 2025 Mar 26:e2024068244. doi: 10.1542/peds.2024-068244.
    PubMed         Abstract available


    PLoS Comput Biol

  16. VON HOENE E, Roess A, Kavak H, Anderson T, et al
    Synthetic population generation with public health characteristics for spatial agent-based models.
    PLoS Comput Biol. 2025;21:e1012439.
    PubMed         Abstract available

  17. WU L, Baker CM, Tierney N, Carville K, et al
    Quantifying the impact of contact tracing interview prioritisation strategies on disease transmission: A modelling study.
    PLoS Comput Biol. 2025;21:e1012906.
    PubMed         Abstract available


    PLoS One

  18. JOSEPH M, Li Q, Shin S
    Health diagnosis associated with COVID-19 death in the United States: A retrospective cohort study using electronic health records.
    PLoS One. 2025;20:e0319585.
    PubMed         Abstract available

  19. BAYOU FD, Getaneh FB, Asmare L, Endawkie A, et al
    Trend of home birth and its associated factors in Ethiopia during COVID-19 and social crisis (2019-2023).
    PLoS One. 2025;20:e0320859.
    PubMed         Abstract available

  20. BUGHIN J, Cincera M, Reykowska D, Zyszkiewicz M, et al
    The great divide between employees: Clustering employee "well-being" during a pandemic.
    PLoS One. 2025;20:e0294540.
    PubMed         Abstract available

  21. PARK H, Miyano S
    Computational network biology analysis revealed COVID-19 severity markers: Molecular interplay between HLA-II with CIITA.
    PLoS One. 2025;20:e0319205.
    PubMed         Abstract available

  22. YOON J, Kim S, Kwon CY, Kang JW, et al
    Kyungok-go for fatigue in patients with long COVID: Double-blind, randomized, multicenter, pilot clinical study protocol.
    PLoS One. 2025;20:e0319459.
    PubMed         Abstract available

  23. LESTARI BW, Saptiningrum E, Huria L, Fikri AR, et al
    Pre-treatment direct costs for people with tuberculosis during the COVID-19 pandemic in different healthcare settings in Bandung, Indonesia.
    PLoS One. 2025;20:e0320401.
    PubMed         Abstract available

  24. YAGIHASHI M, Sakuma A, Murakami M
    Psychotherapies and psychological support for individuals facing psychological distress during the COVID-19 pandemic: A scoping review.
    PLoS One. 2025;20:e0318192.
    PubMed         Abstract available

  25. CARMOLA LR, Roebling AD, Khosravi D, Langsjoen RM, et al
    Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA.
    PLoS One. 2025;20:e0317972.
    PubMed         Abstract available

  26. LIU Y, She R, Xing J
    Analysis of University Students' Mental Health from the Perspective of Occupational Harmony.
    PLoS One. 2025;20:e0309490.
    PubMed         Abstract available

  27. GKEKAS A, Ronaldson SJ, Parker A, Torgerson DJ, et al
    Improving patient recruitment to randomised trials can be cost-effective: A case-study of dexamethasone from the RECOVERY trial.
    PLoS One. 2025;20:e0314593.
    PubMed         Abstract available

  28. SURACE A, Munroe C, Martinez P
    "My drinking was way worse during the pandemic": A qualitative analysis of contextual and individual factors impacting alcohol use during the COVID-19 pandemic.
    PLoS One. 2025;20:e0319977.
    PubMed         Abstract available

  29. AIZAWA T
    Socio-economic gradients in hypertension and diabetes management amid the COVID-19 pandemic in India.
    PLoS One. 2025;20:e0315867.
    PubMed         Abstract available

  30. TAO Z, Ramasamy SS, Naktnasukanjn N, Ying F, et al
    Assessing competitiveness and complementarity in agricultural trade between China and Cambodia pre-pandemic and post-pandemic.
    PLoS One. 2025;20:e0321081.
    PubMed         Abstract available

  31. TREPTOW M, Bartels C, Ruhleder M, Kratzenberg A, et al
    Divergent psychological stress response patterns to the COVID-19 pandemic in psychiatric patients with vs. without PTSD: A real-world exploratory study.
    PLoS One. 2025;20:e0318839.
    PubMed         Abstract available

  32. STUKAS S, Goshua G, Conway EM, Lee AYY, et al
    ABO blood group and COVID-19 severity: Associations with endothelial and adipocyte activation in critically ill patients.
    PLoS One. 2025;20:e0320251.
    PubMed         Abstract available

  33. AWASTHI S, Dehkharghani MZ, Fudolig M
    Emergence to dominance: Estimating time to dominance of SARS-CoV-2 variants using nonlinear statistical models.
    PLoS One. 2025;20:e0311459.
    PubMed         Abstract available

  34. MITCHELL E, Are EB, Colijn C, Earn DJD, et al
    Using artificial intelligence tools to automate data extraction for living evidence syntheses.
    PLoS One. 2025;20:e0320151.
    PubMed         Abstract available


    Proc Natl Acad Sci U S A

  35. GUAY B, Marghetis T, Wong C, Landy D, et al
    Quirks of cognition explain why we dramatically overestimate the size of minority groups.
    Proc Natl Acad Sci U S A. 2025;122:e2413064122.
    PubMed         Abstract available


    Vaccine

  36. OTORBAEVA D, Akmatova R, Cooley KM, Iwamoto C, et al
    Post-introduction evaluation (PIE) of the seasonal influenza vaccination program in Kyrgyzstan in 2023.
    Vaccine. 2025;55:127052.
    PubMed         Abstract available


    Virology

  37. ISHIGAKI H, Itoh Y
    Translational research on pandemic virus infection using nonhuman primate models.
    Virology. 2025;606:110511.
    PubMed         Abstract available

  38. BANGA NDZOUBOUKOU JL, Kamara AA, Ullah N, Lei Q, et al
    A meta-analysis on the immunogenicity of prototype, monovalent-adapted and bivalent vaccines against SARS-CoV-2 wildtype, Omicron BA.1 and Omicron BA.4/5 in healthy adults.
    Virology. 2025;606:110509.
    PubMed         Abstract available

  39. DAS SARMA J
    Murine beta-coronavirus spike protein: A major determinant of neuropathogenic properties.
    Virology. 2025;606:110499.
    PubMed         Abstract available

  40. LUNDRIGAN E, Uguccioni S, Hum C, Ahmed N, et al
    SARS-CoV-2 Nsp13 helicase modulates miR-146a-mediated signaling pathways.
    Virology. 2025;606:110493.
    PubMed         Abstract available

#Mexico: The Ministry of #Health reports the #detection of the first #human case of avian #influenza A (#H5N1)

{Auto translated}

www.gob.mx/salud

The Ministry of Health reports the detection of the first human case of avian influenza A (H5N1) in Mexico

The case occurred in a three-year-old girl residing in the state of Durango. On April 1, the Institute of Epidemiological Diagnosis and Reference (InDRE) confirmed the result of influenza A (H5N1). The patient initially received treatment with oseltamivir and is currently hospitalized in a tertiary care unit in the city of Torreón, where her condition is reported to be serious

Once the case was confirmed, the following actions were immediately implemented: 

-- Notification to the World Health Organization, in accordance with the protocol established for this purpose in the International Health Regulations. 


Health

-- Health personnel from the Durango and Coahuila Health Services were trained in relation to the National Guide for the preparation, prevention and response to a zoonotic influenza outbreak or event at the animal-human interface

-- Intentional search operations were initiated for cases suspected of viral respiratory illness. 


Semarnat - Conanp

-- Biological surveys and sampling of wild and synanthropic birds were carried out in the area of ​​influence surrounding the home of the positive case of avian influenza A (H5N1), and a permanent monitoring system was established for the timely detection of other similar cases in wildlife living in the area.


Agriculture - Senasica

-- The Ministry of Agriculture and Rural Development, through the National Service of Health, Safety, and Agrifood Quality (Senasica), reported that no commercial production units have been affected by avian influenza A (H5N1) in any region of the country. However, Senasica continues its active epidemiological surveillance efforts to promptly identify any potential cases. If so, the corresponding national and international protocols will be implemented.


The Ministry of Health informs the population:

-- The WHO considers the public health risk of this virus to the general population to be low, so eating well-cooked chicken or eggs does not pose a risk to human health. Zoonotic influenza is a disease that can be transmitted from birds or other animals to humans. To date, there is no evidence of sustained human-to-human transmission. 

-- The Ministry of Health has a strategic reserve of 40,000 oseltamivir treatments. 

-- The population is recommended to

- Wash your hands frequently with soap and water or 70 percent alcohol-based solutions. 

- Wear a face mask if you have respiratory symptoms and ventilate spaces. 

- Cover your mouth and nose when coughing or sneezing. 

- Wash your hands before handling cooked foods and after handling raw foods. 

- Cook chicken and eggs properly (over 70°C) 

- Do not use the same utensils to handle raw and cooked foods. 

- Avoid touching or approaching wild animals. 

- Do not handle or pick up dead animals. 

- Do not touch sick or dead birds or poultry due to unknown causes. 

- Wear gloves, face masks, and protective clothing if you work on farms or slaughterhouses and have contact with birds or other animals, their products, and waste. 

-- Monitor for signs of illness or abnormal death in farm or backyard animals and report them immediately to the authorities. 

- The Ministry of Health recommends seeking medical attention if you experience fever, conjunctivitis (burning, itching, redness of the eyes), cough, sore throat, runny nose, difficulty breathing, headache, vomiting, diarrhea, bleeding, or altered consciousness after contact with sick or dead birds or other animals. 

Source: Ministry of Health, https://www.gob.mx/salud/prensa/secretaria-de-salud-informa-la-deteccion-del-primer-caso-humano-de-influenza-aviar-a-h5n1

____

Friday, April 4, 2025

Synergistic effects of PA (S184N) and #PB2 (E627K) #mutations on the increased pathogenicity of #H3N2 canine #influenza virus #infections in mice and #dogs

ABSTRACT

As companion animals, dogs are susceptible to various subtypes of influenza A virus (IAV), with the H3N2 and H3N8 subtypes of canine influenza virus (CIV) stably circulating among canines. Compared to the H3N8 CIV, the H3N2 CIV is more widely prevalent in canine populations and demonstrates increased adaptability to mammals, potentially facilitating cross-species transmission. Therefore, a comprehensive elucidation of the mechanisms underlying H3N2 CIV adaptation to mammals is imperative. In this study, we serially passaged the GD14-WT strain in murine lungs, successfully establishing a lethal H3N2 CIV infection model. From this model, we isolated the lethal strain GD14-MA and identified the key lethal mutations PA(S184N) and PB2(E627K). Moreover, the GD14-ma[PA(S184N)+PB2(E627K)] strain exhibited markedly enhanced pathogenicity in dogs. Viral titers in lung tissues from infected dogs and mice showed that GD14-ma[PA(S184N)+PB2(E627K)] does not increase its pathogenicity to mice and dogs by upregulating viral titers compared to the GD14-WT strain. Notably, sequence alignments across all H3N2 IAVs showed an increasing prevalence of the PA (S184N) and PB2 (E627K) mutations from avian to human hosts. Finally, single-cell RNA sequencing of infected mouse lung tissues showed that GD14-ma[PA(S184N)+PB2(E627K)] effectively evaded host antiviral responses, inducing a robust inflammatory reaction. Considering the recognized role of the PB2 (E627K) mutation in the mammalian adaptation of IAVs, our findings underscore the importance of ongoing surveillance for the PA (S184N) mutation in H3N2 IAVs.


IMPORTANCE

Since the 21st century, zoonotic viruses have frequently crossed species barriers, posing significant global public health challenges. Dogs are susceptible to various influenza A viruses (IAVs), particularly the H3N2 canine influenza virus (CIV), which has stably circulated and evolved to enhance its adaptability to mammals, including an increased affinity for the human-like SAα2,6-Gal receptor, posing a potential public health threat. Here, we simulated H3N2 CIV adaptation in mice, revealed that the synergistic PA(S184N) and PB2(E627K) mutations augment H3N2 CIV pathogenicity in dogs and mice, and elucidated the underlying mechanisms at the single-cell level. Our study provides molecular evidence for adapting the H3N2 CIV to mammals and underscores the importance of vigilant monitoring of genetic variations in H3N2 CIV.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01984-24?af=R

____

#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {as of April 4 '25}


 

{Excerpt}

Time Period: March 23, 2025 - March 29, 2025

-- H5 Detection9 sites (2.2%)

-- No Detection400 sites (97.8%)

-- No samples in last week228 sites




(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/bird-flu/h5-monitoring/index.html

____

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

{England} Backyard flock of 40 chickens. Increased mortality and other clinical signs were reported. Samples tested positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6401

____

#Nirmatrelvir–ritonavir versus placebo–ritonavir in individuals with #longCOVID in the #USA (PAX LC): a double-blind, randomised, placebo-controlled, phase 2, decentralised trial

Summary

Background

The substantial burden of post-COVID-19 condition (also known as long COVID) underscores the need for effective pharmacological interventions. Given that viral persistence has been hypothesised as a potential cause of long COVID, antiviral therapy might offer a promising approach to alleviating long COVID symptoms. We therefore investigated the efficacy, safety, and tolerability of nirmatrelvir–ritonavir for treating long COVID.

Methods

In this phase 2, decentralised, double-blind, randomised controlled trial, adults (aged ≥18 years) from the 48 states across the contiguous USA, with previous documented SARS-CoV-2 infection and long COVID symptoms starting within 4 weeks of initial infection and persisting for at least 12 weeks, were eligible for inclusion. Key exclusion criteria were use of nirmatrelvir–ritonavir within the previous 2 months, CYP3A4-dependent medications, or strong CYP3A4 inducers; acute medical illness such as SARS-CoV-2 infection within the past 2 weeks; active liver disease; renal impairment; and immunocompromise. Using software for 1:1 stratified block random assignment, participants were randomly allocated to receive either two tablets of nirmatrelvir (150 mg each) and one tablet of ritonavir (100 mg), or placebo and one tablet of ritonavir (100 mg), orally administered twice daily for 15 days, stratified by age, sex at birth, and COVID-19 vaccination status. Participants, clinicians, and the study team were masked to treatment allocation. The primary efficacy endpoint was the change in the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Physical Health Summary Score (PHSS) from baseline to day 28, analysed by intention to treat. Safety endpoints were reported from baseline to week 6 in all participants who were exposed to the study treatment. This trial is registered with ClinicalTrials.gov (NCT05668091) and is now closed to new participants.

Findings

Between April 14, 2023, and Feb 26, 2024, 119 participants were screened. 100 were enrolled (66 [66%] female participants and 34 [34%] male participants), with 49 assigned to the nirmatrelvir–ritonavir group and 51 to the placebo–ritonavir group (intention-to-treat population). Three participants in the nirmatrelvir–ritonavir group and two in the placebo–ritonavir group withdrew before starting treatment and were excluded from the safety population. The mean PROMIS-29 PHSS at baseline was 39·6 (95% CI 37·4 to 41·9) in the nirmatrelvir–ritonavir group and 36·3 (34·4 to 38·2) in the placebo–ritonavir group. The adjusted change from baseline to day 28 was 0·45 (–0·93 to 1·83) in the nirmatrelvir–ritonavir group and 1·01 (–0·30 to 2·31) in the placebo–ritonavir group (adjusted mean difference –0·55 [95% CI –2·32 to 1·21; p=0·54]). No deaths or serious adverse events were recorded between baseline and week 6. Study drug-related treatment-emergent adverse events were reported in more participants in the nirmatrelvir–ritonavir group (35 [76%] of 46) compared with the placebo–ritonavir group (27 [55%] of 49), mostly driven by dysgeusia. Early treatment termination due to an adverse event occurred in two participants in the nirmatrelvir–ritonavir group and one in the placebo–ritonavir group.

Interpretation

Nirmatrelvir–ritonavir administered for 15 days did not significantly improve health outcomes in participants with long COVID compared with placebo–ritonavir at day 28. However, the study showed the feasibility of large-scale, decentralised trials in long COVID.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00073-8/fulltext?rss=yes

____

#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

____

#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

____

Thursday, April 3, 2025

#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

____

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

____

#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

____

#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/

____

#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

____

Wednesday, April 2, 2025

#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

____

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

____

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

____

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

____

Tuesday, April 1, 2025

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

____

#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

____


#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

____


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

House Crows in Bihar State.


_____

#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

____

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

____

Monday, March 31, 2025

#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

____

#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

____

#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

____

#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 21 January to 19 March 2025 {WHO}



Influenza at the human-animal interface Summary and risk assessment, from 21 January to 19 March 2025{1} 


New human cases{2}: 

From 21 January to 19 March 2025, based on reporting date, the detection of influenza A(H5N1) in five humans, influenza A(H9N2) virus in four humans, influenza A(H1N1) variant ((H1N1)v) virus in one human, and influenza A(H1N2)v virus in one human were reported officially. 

Circulation of influenza viruses with zoonotic potential in animals: 

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

Risk assessment{5}: 

-- Sustained human to human transmission has not been reported from these events. Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses circulating at the human-animal interface has not changed remains low. The occurrence of sustained human-to-human transmission of these viruses is currently considered unlikely. Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.  

Risk management

-- New candidate vaccine viruses (CVVs) for zoonotic influenza viruses for pandemic preparedness purposes were selected for development at the February 2025 WHO consultation on influenza vaccine composition for use in the northern hemisphere 2025-2026 influenza season. A detailed summary of zoonotic influenza viruses characterized since September 2024 is published here and updated CVVs lists are published here. 

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 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 20 January 2025, one laboratory-confirmed human case of A(H5N1) infection was reported to WHO from Cambodia, one from the United Kingdom of Great Britain and Northern Ireland and three from the United States of America (USA).  

A(H5N1), Cambodia 

On 26 February 2025, Cambodia notified the WHO of a human case of influenza A(H5N1) in a boy from Prey Veng Province. The case had onset of fever, cough and fatigue on 17 February. He was initially seen at a local private clinic and given medication, but as his condition did not improve, he was transferred to Phnom Penh and hospitalized at a private hospital on 20 February. The case’s condition deteriorated, and he developed shortness of breath and was transferred on 24 February to a national hospital, which is a sentinel surveillance site for severe acute respiratory infection (SARI). Upon admission the case was isolated, nasopharyngeal (NP) and oropharyngeal (OP) swab specimens were collected and oseltamivir administered. On 25 February, the specimens tested positive for influenza A(H5N1) by reverse transcription-polymerase chain reaction (RT-PCR) at the National Institute of Public Health of Cambodia. The results were later confirmed by the Institut Pasteur du Cambodge (IPC) on 26 February. Sequence analysis of the HA gene revealed the virus belongs to clade 2.3.2.1e (previously classified as clade 2.3.2.1c){7}, and is similar to viruses circulating among birds, including poultry, and detected in human cases since late 2023 in Cambodia. The case was reported to have had exposure to sick and dead backyard chickens. Samples collected from the backyard chickens tested positive for A(H5N1). The case died on 25 February. No further cases were detected among the contacts of the case. This case is the second human infection with influenza A(H5N1) reported in Cambodia in 2025. 

A(H5N1), United Kingdom  

On 25 January 2025, the United Kingdom reported to WHO the detection of A(H5N1) in one individual in England who was sampled as part of a zoonotic influenza surveillance study launched by the UK Health Security Agency (UKHSA) in March 2023 to monitor people with close contact to infected birds. The individual was recruited to the surveillance study while working at a farm where birds were infected with A(H5N1) viruses and was found to be symptomatic. A sample collected on 23 January was confirmed A(H5)-positive at the national reference laboratory on 24 January. One symptomatic household contact tested negative. Sequencing of virus from the infected birds the case had contact with were determined to be of A(H5N1) clade 2.3.4.4b and the DI.2 genotype, which is prevalent within Europe at the current time. The DI.2 genotype is distinct from the A(H5) clade 2.3.4.4b genotypes that have been detected in North America.{8}  The UKHSA has previously notified WHO (in May, June, and July 2023) about four individuals who tested positive for influenza A(H5) virus as part of the UKHSA Zoonotic Influenza Surveillance Study.{9} 

A(H5N1), USA{10,11,12,13} 

In the USA, one laboratory-confirmed A(H5) infection was reported in an adult from the state of Ohio who worked at a commercial poultry facility where HPAI A(H5N1) virus had been detected in birds and was involved in depopulation activities. The individual had respiratory symptoms, was hospitalized, discharged and recovering at the time of the update. Genetic sequencing of the virus from this individual identified an avian influenza A(H5N1) virus from clade 2.3.4.4.b belonging to the genotype D1.3 genotype and no markers known that would impact the effectiveness of influenza antivirals or existing candidate vaccine viruses or changes associated with mammalian adaptation were identified.  Another laboratory-confirmed A(H5) infection was reported in an adult from the state of Wyoming who had direct contact with poultry infected with avian influenza A(H5) virus that died on their property. The individual was reported to have underlying health conditions that can be risk factors for severe influenza illness. This person has been discharged from the hospital and was recovering at the time of the update. Initial upper respiratory specimens were negative for influenza viruses; a lower respiratory specimen collected several days later in the hospital was positive for avian influenza A(H5N1) virus. Genetic sequencing of the virus from this individual identified an avian influenza A(H5N1) virus from clade 2.3.4.4.b belonging to the genotype D1.1, and the genetic mutation in the polymerase basic 2 (PB2) protein (E627K) that has previously been associated with more efficient virus replication in people and other mammals and has been detected in viruses from past human infections with A(H5) viruses.  Additionally, one laboratory-confirmed case was reported in an adult from the state of Nevada who worked at a commercial dairy cattle farm in an area where HPAI A(H5N1) viruses had been detected in cows. This individual developed conjunctivitis and recovered. Genetic sequencing of the virus from this individual identified an avian influenza A(H5N1) virus from clade 2.3.4.4.b also belonging to genotype D1.1, with a sequence nearly identical to that of the viruses that USDA reported from dairy cows in Nevada that the person worked with.{14} Sequencing also identified the D701N genetic mutation in the PB2 protein that has previously been associated with more efficient virus replication in mammalian cells and has been detected in viruses from past human infections with A(H5) viruses. Low pathogenicity and high pathogenicity avian influenza viruses have been detected in birds in the United States.  Since 2022, the HPAI A(H5) virus has been detected in commercial and backyard flocks in 48 states, impacting over 100 million birds. To date, 71 people have tested positive for A(H5) virus in the United States since 2022, with all but one of these cases occurring in 2024. All cases have been associated with exposure to either A(H5N1)-infected poultry or dairy cattle, except for two cases where the exposure source could not be identified.{15} To date, no human-to-human transmission of influenza A(H5) virus has been identified in the USA. A(H5N1) virus infections in dairy cattle and wild and domestic birds continue to be reported in the USA.{16} According to reports received by WOAH, various influenza A(H5) subtypes continue to be detected in wild and domestic birds in the Americas, Asia and Europe. Infections in non-human mammals are also reported, including in marine and land mammals.{17} A list of bird and mammalian species affected by HPAI A(H5) viruses is maintained by FAO.{18}


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 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 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 influenza A(H5) viruses circulating have not acquired the ability to efficiently transmit between people, therefore the likelihood of sustained human-to-human 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 20 January 2025, four human cases of infection with A(H9N2) influenza viruses were notified to WHO from China on 7 February 2025. All four cases were detected through the influenza-like illness (ILI) surveillance system. The cases were detected in Guangdong (one), Hunan (two) and Sichuan (one) provinces. One case, in an adult, had underlying conditions at the time of illness and was hospitalized with pneumonia. The other cases (two children and one adult) had mild illnesses. Each case had a known history of exposure to poultry prior to the onset of symptoms. Environmental samples collected from areas associated with two cases (live poultry markets) tested positive for influenza A(H9) virus while samples from the environments associated with the other two cases (backyard areas) tested negative. 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 in most cases. 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 continues in Africa and Asia{19}, 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.  


Swine Influenza Viruses   

Current situation:    

Since the last risk assessment of 20 January 2025, one detection of an influenza A(H1N1)v virus was reported from China and one detection of an influenza A(H1N2)v was reported from the USA.  


Influenza A(H1N1)v, China 

On 7 February 2025, China notified WHO of a human case of Eurasian avian-like swine influenza A(H1N1) virus in a child from Yunnan Province. She developed mild upper respiratory tract symptoms on 12 November 2024 and a respiratory sample was collected on 13 November 2024 as part of routine influenza-like illness (ILI) surveillance. Close contacts remained asymptomatic and tested negative for influenza. She had exposure to backyard pigs however samples collected from the pigs tested negative for Eurasian avian-like swine influenza A(H1N1) viruses. The virus from this case was a clade 1C.2.3 virus. 


Influenza A(H1N2)v, USA  

A laboratory-confirmed human infection with an influenza A(H1N2)v virus was reported in an adult from the state of Iowa. The individual sought health care during the week ending 18 January 2025, was hospitalized, and recovered. An investigation by public health officials did not identify direct or indirect swine contact. No further cases were identified associated with this case. The virus from this case belonged to clade 1B.2.1 which is known to circulate in swine in the USA. 


Risk Assessment:   

1. What is the public health risk of additional human cases of infection with swine influenza viruses?    

-- Swine influenza viruses circulate in swine populations in many regions of the world. Depending on geographic location, the genetic characteristics of these viruses differ. Most human cases are exposed to swine influenza viruses through contact with infected animals or contaminated environments. Human infection tends to result in mild clinical illness in most cases. Since these viruses continue to be detected in swine populations, further human cases are expected but remain unusual. The impact for public health if additional cases are detected is minimal. The overall risk of additional human cases is low.    

2. What is the likelihood of sustained human-to-human transmission of swine influenza viruses?    

-- No sustained human-to-human transmission was identified associated with the events described above. Current evidence suggests that contemporary swine influenza viruses 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 swine influenza viruses by travelers?    

-- 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 suggest that these viruses have not acquired the ability to transmit easily among humans.   

For more information on zoonotic viruses, see the report from the WHO Consultation on the Composition of Influenza Virus Vaccines for Use in the 2025-2026 Northern Hemisphere Influenza Season held on 24-27 February 2025 at the following link: Antigenic and genetic characteristics of zoonotic influenza A viruses and development of candidate vaccine viruses for pandemic preparedness in the 2025-2026 northern hemisphere influenza season.  


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. 

• 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.{20}  

• 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).{21} State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed{22} case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic{23}. 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{24} 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/ 

____

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

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

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

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

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

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

{7} 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: 10.1101/2025.01.07.631789. PMID: 39829835; PMCID: PMC11741357. 

{8} UKHSA. Human case of avian flu detected in England, 27 January 2025. Available at: https://www.gov.uk/government/news/human-case-of-avian-flu-detected-in-england. 

{9} UKHSA. Investigation into the risk to human health of avian influenza (influenza A H5N1) in England: technical briefing 5, Updated 14 July 2023. Available at: https://www.gov.uk/government/publications/avian-influenzainfluenza-a-h5n1-technical-briefings/investigation-into-the-risk-to-human-health-of-avian-influenza-influenzaa-h5n1-in-england-technical-briefing-5. 

{10} US CDC. Weekly US Influenza Surveillance Report: Key Updates for Week 6, ending February 8, 2025. Available at: https://www.cdc.gov/fluview/surveillance/2025-week-06.html. 

{11} US CDC. Weekly US Influenza Surveillance Report: Key Updates for Week 7, ending February 15, 2025. Available at:  https://www.cdc.gov/fluview/surveillance/2025-week-07.html. 

{12} US CDC. CDC A(H5N1) Bird Flu Response Update, February 26, 2025. Available at: https://www.cdc.gov/birdflu/spotlights/h5n1-response-02262025.html. 

{13} US CDC. CDC A(H5N1) Bird Flu Response Update March 19, 2025. Available at https://www.cdc.gov/birdflu/spotlights/h5n1-response-03192025.html. 

{14} USDA. The Occurrence of Another Highly Pathogenic Avian Influenza (HPAI) Spillover from Wild Birds into Dairy Cattle. Available at:https://www.aphis.usda.gov/sites/default/files/dairy-cattle-hpaitech-brief.pdf 

{15} United States Centers for Disease Control and Prevention. H5 Bird Flu: Current Situation. Available at: https://www.cdc.gov/bird-flu/situationsummary/index.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fbird-flu%2Fphp%2Favian-flusummary%2Findex.html. 

{16}  United States Department of Agriculture. Highly Pathogenic Avian Influenza (HPAI) Detections in Livestock, 19 July 2024. Available at: https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpaidetections/livestock. 

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

{18} 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. 

{19} 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. 

{20} 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/. 

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

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

{23} 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 

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

Source: World Health Organization, https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment-19-march-2025

____

My New Space

Most Popular Posts