Sustained circulation of #enterovirus D68 in #Europe in 2023 and continued #evolution of #EVD68 B3-lineages associated with distinct amino acid substitutions in VP1 protein

Highlights

• Enterovirus D68 (EV-D68) was circulating in Europe in 2023

• Most EV-D68 cases were captured through clinical EV surveillance

• Phylogenetic analysis of the VP1 region revealed a distinct B3-derived lineage

• The identified B3 lineage presented a previously undescribed residue change, D554E

Abstract

Background

Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution.

Study design

Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis.

Results

EV was detected in 13585 out of 203622 diagnostic samples tested (6.7%), of which 402 (3.0%) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2%). 267/386 (69.2%) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe.

Conclusions

The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000277?dgcid=rss_sd_all

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Judith, Giorgione (1504)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/giorgione/judith

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Development of an Intranasally- and Intramuscularly-Administrable #Replicon #Vaccine Efficacious Against #H5N1 #Influenza Virus

Abstract

The risk of a respiratory viral pandemic is significant, including from the now widespread panzootic H5N1 influenza virus, highlighting the need for effective, stable, and inexpensive vaccine technologies that elicit strongly protective immunity. Intranasal vaccines can stimulate local immune responses at the site of natural respiratory viral infection, a key characteristic that can not only reduce morbidity and mortality caused by respiratory viruses but also potentially reduce viral transmissibility to limit outbreaks. Nucleic acid vaccines are now a valuable tool in pandemic responses, with high potency and rapid adaptability to target circulating or emerging viral strains; however, data are limited on which vaccine attributes are needed for efficient transmucosal delivery and immune stimulation following intranasal delivery. To demonstrate proof of concept, here we have developed a replicon vaccine expressing an H5 influenza antigen that uses a nanostructured lipid carrier (NLC) delivery system. A relationship was established between the molar ratio of positive charges on the NLC to the negative charges on the nucleic acid (N:P ratio) and the immunogenicity of the vaccine formulations, with higher N:P ratios resulting in an increase in vaccine immunogenicity. We demonstrated the ability of this replicon vaccine to be administered via intramuscular and intranasal routes with a singular vaccine formulation. The vaccine induced systemic immunity when dosed intramuscularly or intranasally in an immunocompetent mouse model, whereas intranasal dosing uniquely stimulated a strong mucosal immune response. Moreover, a mixed intramuscular/intranasal dosing strategy using this unified formulation stimulated a balanced systemic and mucosal immune response. Finally, we demonstrated the protective efficacy of this intranasally and intramuscularly/intranasally delivered H5 replicon-NLC vaccine against morbidity and mortality in a lethal H5N1 influenza challenge ferret model. This work establishes the replicon-NLC vaccine platform as a potential novel intranasal technology for rapid pandemic response.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.31.646478v1

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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

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#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

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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

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#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 Detection: 9 sites (2.2%)

-- No Detection: 400 sites (97.8%)

-- No samples in last week: 228 sites

(...)

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

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#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

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#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

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#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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