Monday, March 17, 2025

#USA - High pathogenicity avian #influenza #H7N9 viruses (#poultry) (Inf. with) - Immediate notification

Highly pathogenic avian influenza (HPAI) H7N9 of North American wild bird lineage was detected in a commercial broiler breeder chicken flock in Mississippi. Depopulation of the affected flock is in progress. The USDA Animal and Plant Health Inspection Service (APHIS), in conjunction with State Animal Health and Wildlife Officials, are conducting a comprehensive epidemiological investigation and enhanced surveillance in response to the detection.

A commercial broiler breeder premises {in Mississippi}. Clinical signs included increased mortality. Depopulation was completed 13 Mar 2025.

Source: WOAH, https://wahis.woah.org/#/in-review/6340

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Sunday, March 16, 2025

Superior #replication, #pathogenicity, and immune #evasion of a #Texas dairy #cattle #H5N1 virus compared to a historical avian isolate

Abstract

The current outbreak of highly pathogenic avian influenza (HPAI) viruses of the H5N1 subtype clade 2.3.4.4b in dairy cattle in the United States has affected nearly 900 dairy farms and resulted in at least 39 human infections, putting health authorities and the scientific community on high alert. Here we characterize the virus growth properties and host-pathogen interactions of an isolate obtained from a sick dairy cow in Texas in vitro and in vivo and compare it to an older HPAI isolate. Despite so far being associated with mild disease in human patients, the cattle H5N1 virus showed superior growth capability and rapid replication kinetics in a panel of human lung cell lines in vitro. In vivo, cattle H5N1 exhibited more intense pathogenicity in mice, with rapid lung pathology and high virus titers in the brain, accompanied by high mortality after challenge via different inoculation routes. Additionally, the cattle H5N1 demonstrated efficient antagonism of overexpressed RIG-I- and MDA5-mediated innate antiviral signaling pathways. In summary, this study demonstrates the profound pathogenicity and suggests a potential innate immune escape mechanism of the H5N1 virus isolated from a dairy cow in Texas.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-93493-5

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Saturday, March 15, 2025

#Coronavirus Disease Research #References (by AMEDEO, March 15 '25)

 


    Am J Obstet Gynecol

  1. TAN YY, Loy EXH, Tan WZ, Tay AT, et al
    Long COVID-19 in pregnancy: increased risk but modest incidence following mild Omicron infection in a boosted obstetric cohort during endemicity.
    Am J Obstet Gynecol. 2025 Mar 10:S0002-9378(25)00147.
    PubMed         Abstract available


    BMJ

  2. IACOBUCCI G
    Covid-19: Gove tried to "circumvent" regulations to buy Dyson ventilators, inquiry hears.
    BMJ. 2025;388:r502.
    PubMed        


    Clin Infect Dis

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    A systematic review and meta-analysis of the effectiveness of remdesivir to treat SARS-CoV-2 infection in hospitalized patients: have the guidelines evolved with the evidence?
    Clin Infect Dis. 2025 Mar 11:ciaf111. doi: 10.1093.
    PubMed         Abstract available

  4. COX SN, Roychoudhury P, Frivold C, Acker Z, et al
    Household Transmission and Genomic Diversity of Respiratory Syncytial Virus (RSV) in the United States, 2022-2023.
    Clin Infect Dis. 2025 Mar 14:ciaf048. doi: 10.1093.
    PubMed         Abstract available

  5. KELLY JD, Hoggatt KJ, Lo NC, Leonard S, et al
    Annual variant-targeted vaccination to prevent severe COVID-19 disease in cohorts with vaccine-derived and hybrid immunity.
    Clin Infect Dis. 2025 Mar 14:ciaf124. doi: 10.1093.
    PubMed         Abstract available

  6. ROCKSTROH JK, Paredes R, Cahn P, Molina JM, et al
    Doravirine/islatravir (100/0.75 mg) once-daily compared to bictegravir/emtricitabine/tenofovir alafenamide as initial HIV-1 treatment: 48-week results from a phase 3, randomized, controlled, double-blind, non-inferiority trial.
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    PubMed         Abstract available


    Int J Infect Dis

  7. LI Z, Wang Z, Wang X, Chen S, et al
    Global containment policy duration and long-term epidemic progression: a target trial emulation using COVID-19 data from 2020 to 2022.
    Int J Infect Dis. 2025 Mar 5:107871. doi: 10.1016/j.ijid.2025.107871.
    PubMed         Abstract available

  8. MADEWELL ZJ, Wong JM, Thayer MB, Rivera-Amill V, et al
    Population-level respiratory virus-virus interactions, Puerto Rico, 2013-2023.
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    PubMed         Abstract available


    J Infect

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    Understanding the Effectiveness of the Comirnaty Monovalent and Bivalent Vaccines During the Winter Coronavirus (COVID-19) Infection Survey.
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    PubMed         Abstract available


    J Med Virol

  10. AZANZA JR, Gonzalez Del Castillo JM, Ferrando R, Molero JM, et al
    Cost-Effectiveness of Nirmatrelvir/Ritonavir in COVID-19 Patients at High-Risk for Progression in Spain.
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    PubMed         Abstract available

  11. LIU S, Liu P, Lu Q, Shen Y, et al
    The Compensatory Effect of S375F on S371F Is Vital for Maintaining the Infectivity of SARS-CoV-2 Omicron Variants.
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    PubMed         Abstract available

  12. GARCIA-VIDAL C, Teijon-Lumbreras C, Aiello TF, Chumbita M, et al
    COVID-19 Patients Benefitting From Remdesivir for Improved Survival: A Neural Network-Based Approach.
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    PubMed         Abstract available


    JAMA

  13. LAURING AS, Edson C, Surie D, Dawood FS, et al
    Genomic Characterization of RSV in the US by Vaccination Status.
    JAMA. 2025 Mar 10. doi: 10.1001/jama.2025.1225.
    PubMed        


    Lancet

  14. SINGH B, Lipunga GD, Thangavelu P, Dhar S, et al
    A multifaceted intervention to improve diagnosis and early management of hospitalised patients with suspected acute brain infections in Brazil, India, and Malawi: an international multicentre intervention study.
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    PubMed         Abstract available

  15. WEISS DJ, Dzianach PA, Saddler A, Lubinda J, et al
    Mapping the global prevalence, incidence, and mortality of Plasmodium falciparum and Plasmodium vivax malaria, 2000-22: a spatial and temporal modelling study.
    Lancet. 2025 Mar 5:S0140-6736(25)00038-8. doi: 10.1016/S0140-6736(25)00038.
    PubMed         Abstract available


    Nature

  16. GOETZKE CC, Massoud M, Frischbutter S, Guerra GM, et al
    TGFbeta links EBV to multisystem inflammatory syndrome in children.
    Nature. 2025 Mar 12. doi: 10.1038/s41586-025-08697.
    PubMed         Abstract available

  17. CALLAWAY E
    Four ways COVID changed virology: lessons from the most sequenced virus of all time.
    Nature. 2025;639:293-295.
    PubMed        


  18. Immune molecule links COVID?19 with severe inflammatory disorder in children.
    Nature. 2025 Mar 12. doi: 10.1038/d41586-025-00735.
    PubMed        


    Pol J Radiol

  19. HAJSADEGHI S, Kasaei M, Pouraliakbar H, Jamalkhani S, et al
    Comparing myocardial injury patterns and outcomes in cardiac magnetic resonance imaging between COVID-19- and non-COVID-19-related myocarditis.
    Pol J Radiol. 2025;90:e36-e45.
    PubMed         Abstract available


    Science

  20. WADMAN M
    No sign that vaccine advisers are beholden to industry.
    Science. 2025;387:1131-1132.
    PubMed         Abstract available

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, March 15 '25)

 


    Biochemistry (Mosc)

  1. FILIPPOVA TA, Masamrekh RA, Farafonova TE, Khudoklinova YY, et al
    Determination of SARS-CoV-2 Main Protease (M(pro)) Activity Based on Electrooxidation of Tyrosine Residue of a Model Peptide.
    Biochemistry (Mosc). 2025;90:120-131.
    PubMed         Abstract available


    BMC Pediatr

  2. JAYARATNE K, Illangasinghe P, Wanniarachchi S, Hettiarachchi D, et al
    Epidemic profile of COVID-19 child deaths in Sri Lanka: a retrospective nationwide analysis.
    BMC Pediatr. 2025;25:174.
    PubMed         Abstract available


    Cell

  3. XING L, Liu Z, Wang X, Liu Q, et al
    Early fusion intermediate of ACE2-using coronavirus spike acting as an antiviral target.
    Cell. 2025;188:1297-1314.
    PubMed         Abstract available


    J Epidemiol Community Health

  4. COSTE M, Prah JJ
    Applying the health capability profile: an analytical study of leading causes of death in the USA and of pressing public health issues.
    J Epidemiol Community Health. 2025;79:302-310.
    PubMed         Abstract available

  5. AGARWAL G, Keshavarz H, Angeles R, Pirrie M, et al
    SARS-CoV-2 testing, test positivity and vaccination in social housing residents compared with the general population: a retrospective population-based cohort study.
    J Epidemiol Community Health. 2025;79:233-238.
    PubMed         Abstract available

  6. JIN H, Lee WJ, Maupin D, Lee JO, et al
    Within-person relationship between employment insecurity and mental health: a longitudinal analysis of the Understanding America Study.
    J Epidemiol Community Health. 2025;79:265-271.
    PubMed         Abstract available


    J Immunol

  7. GROVENSTEIN P, Bhatnagar N, Kim KH, Pal SS, et al
    Influenza 5xM2e mRNA lipid nanoparticle vaccine confers broad immunity and significantly enhances the efficacy of inactivated split vaccination when coadministered.
    J Immunol. 2025;214:104-114.
    PubMed         Abstract available

  8. QIAO P, Yue C, Peng W, Liu K, et al
    Precise motif and cross-presentation of coronavirus peptides by feline MHC class I: implications for the mild infection of SARS-CoV-2.
    J Immunol. 2025;214:115-129.
    PubMed         Abstract available

  9. WANG M, Liu C, Fan Q, Sun Y, et al
    Rapid clonal expansion and somatic hypermutation contribute to the fate of SARS-CoV-2 broadly neutralizing antibodies.
    J Immunol. 2025;214:278-289.
    PubMed         Abstract available


    J Infect Dis

  10. VILLALOBOS RODRIGUEZ AP, Wellington Perkins I, Moosavi S, de la Garza A, et al
    Pandemic Preparedness: Analyzing National Plans for Respiratory Pathogen Pandemics in the Americas Region.
    J Infect Dis. 2025;231.
    PubMed         Abstract available

  11. REDONDO-BRAVO L, Zureick K, Voto C, Molina Avendano X, et al
    A Comparative Analysis of Universal and Sentinel Surveillance Data for Coronavirus Disease 2019: Insights From Argentina, Chile, and Mexico (2020-2022).
    J Infect Dis. 2025;231.
    PubMed         Abstract available

  12. RODRIGUEZ A, Couto P, Acevedo A, Herrera BA, et al
    Strengthening the Surveillance and Response to Public Health Events With a One Health Approach: A Perspective From 12 Countries in Latin America and the Caribbean.
    J Infect Dis. 2025;231.
    PubMed         Abstract available


    JAMA

  13. MAIA IS, Kawano-Dourado L, Tramujas L, de Oliveira NE, et al
    High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial.
    JAMA. 2024 Dec 10. doi: 10.1001/jama.2024.26244.
    PubMed         Abstract available


    MMWR Morb Mortal Wkly Rep

  14. ZHU S, Harriman K, Liu C, Kraushaar V, et al
    Human Cases of Highly Pathogenic Avian Influenza A(H5N1) - California, September-December 2024.
    MMWR Morb Mortal Wkly Rep. 2025;74:127-133.
    PubMed         Abstract available


    PLoS Comput Biol

  15. AMARAL AVR, Wolffram D, Moraga P, Bracher J, et al
    Post-processing and weighted combination of infectious disease nowcasts.
    PLoS Comput Biol. 2025;21:e1012836.
    PubMed         Abstract available


    PLoS Med

  16. AHMADI-ABHARI S, Bandosz P, Shipley MJ, Lindbohm JV, et al
    Direct and indirect impacts of the COVID-19 pandemic on life expectancy and person-years of life lost with and without disability: A systematic analysis for 18 European countries, 2020-2022.
    PLoS Med. 2025;22:e1004541.
    PubMed         Abstract available


    PLoS One

  17. ADAMU H, Lawal S, Bawa IA, Sani AM, et al
    Prevalence and pattern of adverse events following COVID-19 vaccination among adult population in Sokoto metropolis, northwest, Nigeria.
    PLoS One. 2025;20:e0277585.
    PubMed         Abstract available

  18. GONCALVES NV, Leal AL, Guimaraes HMMES, Bernardes AC, et al
    The territorialization of Severe Acute Respiratory Syndrome and its socioeconomic, demographic and public health policy risk factors in Belem, state of Para, Eastern Amazon, Brazil: a cross-sectional and ecological study.
    PLoS One. 2025;20:e0318607.
    PubMed         Abstract available

  19. DEGUCHI Y, Iwasaki S, Uesaka Y, Okawa Y, et al
    Remote work and long-term sickness absence due to mental disorder trends among Japanese workers pre/post COVID-19.
    PLoS One. 2025;20:e0319825.
    PubMed         Abstract available

  20. HTET H, Wichaidit W, Chuaychai A, Sottiyotin T, et al
    Perspectives of stakeholders on barriers to COVID-19 protective behaviors adherence and vaccination among Myanmar migrant workers in southern Thailand: A qualitative study.
    PLoS One. 2025;20:e0317714.
    PubMed         Abstract available

  21. MOHRI P, Koyluoglu YO, Seker ME, Sancak SN, et al
    Medical students' perception of paid E-learning.
    PLoS One. 2025;20:e0317340.
    PubMed         Abstract available


    Proc Natl Acad Sci U S A

  22. WANG Q, Xu S, Shen W, Wei Y, et al
    N6-methyladnosine of vRNA facilitates influenza A virus replication by promoting the interaction of vRNA with polymerase proteins.
    Proc Natl Acad Sci U S A. 2025;122:e2411554122.
    PubMed         Abstract available


    Vaccine

  23. KRAMMER F
    Next-generation seasonal influenza virus vaccines need a neuraminidase component.
    Vaccine. 2025;54:126994.
    PubMed        

  24. OTIENO NA, Kalani R, Ayugi J, Nyawanda BO, et al
    Seasonal influenza vaccination in Kenya: What determines healthcare Workers' willingness to accept and recommend vaccination?
    Vaccine. 2025;54:126963.
    PubMed         Abstract available


    Virology

  25. OSPINA-JIMENEZ AF, Gomez AP, Rincon-Monroy MA, Perez DR, et al
    A novel reassorted swine H3N2 influenza virus demonstrates an undetected human-to-swine spillover in Latin America and highlights zoonotic risks.
    Virology. 2025;606:110483.
    PubMed         Abstract available

  26. PAWAR SD, Keng SS, Tare DS, Balakrishnan A, et al
    Evidence of novel reassortment in clade 2.3.4.4b avian influenza H5N1 viruses, India, 2024.
    Virology. 2025;606:110482.
    PubMed         Abstract available

Altered #receptor-binding #specificity of #gull-adapted #H13 avian #influenza viruses corresponds to their unique host preferences

Highlights

• H13 HAs exhibit binding specificity for fucosylate α2-3 sialosides.

• The 130-loop and K227 are critical for H13 HA binding specificity.

• Fucosylated α2-3 sialosides are widely distributed in slaty-backed gulls.


Abstract

Avian influenza viruses (AIVs) recognize α2-3 sialosides as receptors. Previous studies showed that the structural diversity within α2-3 sialosides is related to the host specificity of AIVs. H13 AIVs are primarily isolated from gulls, although almost all AIV subtypes have been isolated from ducks, the natural hosts of AIVs. To elucidate the molecular basis of the host specificity of H13 viruses to gulls, the receptor-binding specificity of H13 hemagglutinins (HAs) and the distribution of viral receptors in gulls were investigated. The results revealed that recombinant HA (rHA) of H13 viruses had a binding preference for fucosylated α2-3 sialosides, which were distributed widely in the respiratory tract and intestines of gulls but not in the colon of ducks. Moreover, the receptor-binding specificity of mutant rHAs revealed that amino acids in the 130-loop and at position 227 of H13 HA were critical for the preference for fucosylated α2-3 sialosides. The results of the present study suggest that the binding specificity of H13 HA to fucosylated α2-3 sialosides is a key factor for the host susceptibility of H13 viruses to gulls.

Source: Virology, https://www.sciencedirect.com/science/article/abs/pii/S0042682225000728?via%3Dihub

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Friday, March 14, 2025

Prevalence of #EBV, #HHV6, #HCMV, #HAdV, #SARS-CoV-2, and #Autoantibodies to Type I #Interferon in #Sputum from Myalgic Encephalomyelitis / #CFS Patients

Abstract

An exhausted antiviral immune response is observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-SARS-CoV-2 syndrome, also termed long COVID. In this study, potential mechanisms behind this exhaustion were investigated. First, the viral load of Epstein–Barr virus (EBV), human adenovirus (HAdV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV6), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was determined in sputum samples (n = 29) derived from ME/CFS patients (n = 13), healthy controls (n = 10), elderly healthy controls (n = 4), and immunosuppressed controls (n = 2). Secondly, autoantibodies (autoAbs) to type I interferon (IFN-I) in sputum were analyzed to possibly explain impaired viral immunity. We found that ME/CFS patients released EBV at a significantly higher level compared to controls (p = 0.0256). HHV6 was present in ~50% of all participants at the same level. HAdV was detected in two cases with immunosuppression and severe ME/CFS, respectively. HCMV and SARS-CoV-2 were found only in immunosuppressed controls. Notably, anti-IFN-I autoAbs in ME/CFS and controls did not differ, except in a severe ME/CFS case showing an increased level. We conclude that ME/CFS patients, compared to controls, have a significantly higher load of EBV. IFN-I autoAbs cannot explain IFN-I dysfunction, with the possible exception of severe cases, also reported in severe SARS-CoV-2. We forward that additional mechanisms, such as the viral evasion of IFN-I effect via the degradation of IFN-receptors, may be present in ME/CFS, which demands further studies.

Source: Viruses, https://www.mdpi.com/1999-4915/17/3/422

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#USA, Monitoring for Avian #Influenza A(#H5) Virus In #Wastewater {as of March 14 '25}


 

Time Period: March 02 - March 08, 2025

- H5 Detection29 sites (6.2%)

- No Detection438 sites (93.8%)

- No samples in last week152 sites




(...)

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

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An #overview of #influenza #H5 #vaccines

{Summary}

Pandemic influenza remains a significant global health threat, as signalled by the circulation and cross-species transmission of avian influenza A(H5N1) viruses from the clade 2.3.4.4b, including among dairy cattle in the USA since 2024. Although most of the reported human infections from the USA so far1,2 have been mild, the virus can change its profile rapidly. To reduce mortality and morbidity from influenza in humans, vaccines remain the most important intervention.

(...)


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Thursday, March 13, 2025

Direct and indirect #impacts of #COVID19 #pandemic on #life #expectancy and person-years of life lost with & without #disability: A systematic analysis for 18 European countries, 2020–22

Abstract

Background

The direct and indirect impacts of the COVID-19 pandemic on life expectancy (LE) and years of life lost with and without disability remain unclear. Accounting for pre-pandemic trends in morbidity and mortality, we assessed these impacts in 18 European countries, for the years 2020–2022.

Methods and Findings

We used multi-state Markov modeling based on several data sources to track transitions of the population aged 35 or older between eight health states from disease-free, combinations of cardiovascular disease, cognitive impairment, dementia, and disability, through to death. We quantified separately numbers and rates of deaths attributable to COVID-19 from those related to mortality from other causes during 2020–2022, and estimated the proportion of loss of life expectancy and years of life with and without disability that could have been avoided if the pandemic had not occurred. Estimates were disaggregated by COVID-19 versus non-COVID causes of deaths, calendar year, age, sex, disability status, and country. We generated the 95% uncertainty intervals (UIs) using Monte Carlo simulations with 500 iterations. Among the 289 million adult population in the 18 countries, person-years of life lost (PYLL) in millions were 4.7 (95% UI 3.4–6.0) in 2020, 7.1 (95% UI 6.6–7.9) in 2021, and 5.0 (95% UI 4.1–6.2) in 2022, totaling 16.8 (95% UI 12.0–21.8) million. PYLL per capita varied considerably between the 18 countries ranging between 20 and 109 per 1,000 population. About 60% of the total PYLL occurred among persons aged over 80, and 30% in those aged 65–80. If the pandemic were avoided, over half (9.8 million (95% UI 4.7–15.1)) of the 16.8 million PYLL were estimated to have been lived without disability. Of the total PYLL, 11.6–13.2 million were due to registered COVID-19 deaths and 3.6–5.3 million due to non-COVID mortality. Despite a decrease in PYLL attributable to COVID-19 after 2021, PYLL associated with other causes of death continued to increase from 2020 to 2022 in most countries. Lower income countries had higher PYLL per capita as well as a greater proportion of disability-free PYLL during 2020–2022. Similar patterns were observed for life expectancy. In 2021, LE at age 35 (LE-35) declined by up to 2.8 (95% UI 2.3–3.3) years, with over two-thirds being disability-free. With the exception of Sweden, LE-35 in the studied countries did not recover to 2019 levels by 2022.

Conclusions

The considerable loss of life without disability and the rise in premature mortality not directly linked to COVID-19 deaths during 2020–2022 suggest a potential broader, longer-term and partially indirect impact of the pandemic, possibly resulting from disruptions in healthcare delivery and services for non-COVID conditions and unintended consequences of COVID-19 containment measures. These findings highlight a need for better pandemic preparedness in Europe, ideally, as part of a more comprehensive global public health agenda.

Source: PLoS Medicine, https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004541

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#Ukraine - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

Captive birds: 39 chickens, 23 ducks, 17 pheasants, 4 swans, 3 guinea fowls, 3 geese, 2 pigeons, 1 jay, 1 falcon in Kharkiv Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6329

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#Human Cases of Highly Pathogenic Avian #Influenza A(#H5N1) — #California, September–December 2024

Summary

-- What is already known about this topic?

Persons with occupational exposure to highly pathogenic avian influenza (HPAI) A(H5N1) virus–infected dairy cattle are at increased risk for infection.

-- What is added by this report?

During September 30–December 24, 2024, a total of 38 persons received a positive test result for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows. One, a person aged <18 years with an undetermined exposure, was the first pediatric patient detected with influenza A(H5) infection in the United States.

-- What are the implications for public health practice?

Public health agencies should investigate influenza-like illness or conjunctivitis in workers with occupational exposure to animals infected with HPAI A(H5N1) virus. Thorough investigations of all human HPAI A(H5N1) virus infections are necessary to identify potential exposure sources, including monitoring the virus for concerning genetic changes that indicate the potential for person-to-person transmission.


Abstract

Persons who work closely with dairy cows, poultry, or other animals with suspected or confirmed infection with highly pathogenic avian influenza (HPAI) A(H5N1) viruses are at increased risk for infection. In September 2024, the California Department of Public Health was notified of the first human case of HPAI A(H5N1) in California through monitoring of workers on farms with infected cows. During September 30–December 24, 2024, a total of 38 persons received positive test results for HPAI A(H5N1) viruses in California; 37 were dairy farm workers with occupational exposure to sick cows, and one was a child aged <18 years with an undetermined exposure, the first pediatric HPAI A(H5N1) case reported in the United States. All patients had mild illness. The identification of cases associated with occupational exposure to HPAI A(H5N1) viruses on dairy farms highlights the continued risk for persons who work with infected animals. The pediatric case was identified through routine surveillance. Given recent increases in the prevalence of HPAI A(H5N1) viruses among some animal populations, public health agencies should continue to investigate cases of HPAI A(H5N1) in humans as part of control measures, pandemic preparedness, to identify concerning genetic changes, and to prevent and detect potential human-to-human transmission of the virus. To date, no human-to-human transmission of HPAI A(H5N1) virus has been identified in the United States.

Source: US Centers for Disease Control and Prevention (MMWR), http://dx.doi.org/10.15585/mmwr.mm7408a1

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The Novel #H10N3 Avian #Influenza Virus Triggers Lethal #Cytokine #Storm by Activating Multiple Forms of Programmed Cell Death in Mammalian #Lungs

Abstract

The novel H10N3 avian influenza virus (AIV) has infected four individuals since 2021 and caused severe respiratory damage, posing a significant threat to public health. However, its pathogenic mechanisms remain poorly understood. Our findings revealed that H10N3 infection induces severe lung damage and causes death in mice, even at low doses. The elevated levels of multiple pro-inflammatory factors in the bronchoalveolar lavage fluid were significantly increased during infection, displaying hallmarks of a cytokine storm. Transcriptome sequencing further revealed systematic activation of inflammation-related pathways, predicting that viral infection induces multiple forms of programmed cell death, including apoptosis, pyroptosis, and necroptosis. Protein-level validation showed that the activation of key cell death markers, including Caspase-3, GSDMD, and MLKL, significantly increased as the infection progressed, with their dynamic changes correlating strongly with the expression pattern of viral proteins. This study elucidates the central role of the synergistic effect between the cytokine storm and multiple cell death pathways in H10N3 pathogenesis. These findings not only advance our understanding of the pathogenic mechanisms of AIVs but also provide a critical theoretical basis for the development of targeted therapeutic strategies.

Source: International Journal of Molecular Sciences, https://www.mdpi.com/1422-0067/26/5/1977

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Antigenicity and genetic #properties of an #Eurasian #avian-like #H1N1 swine #influenza virus in #Jiangsu Province, #China

Highlights

• Scientific questionCross-species transmission of influenza A viruses from swine to humans occurs occasionally because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors. In 2011, the first human case of swine influenza virus infection in the mainland of China was detected in Jiangsu Province. Subsequently, the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIV) had sporadically crossed the host barrier and infected humans, raising public concern for its pandemic potential.

• Evidence before this studyA/Jiangsu/1/2011 (H1N1v) was first discovered in 2011 and belongs to the G1 genotype. The G4 and G5 genotypes that appeared successively in 2013 are recombinant H1N1 swine influenza viruses. The EAH1N1 SIVs from 2016 to the present are dominated by the G4 genotype, with hemagglutination (HA) and neuraminidase (NA) genes derived from the EAH1N1 SIVs, non-structural protein (NS) genes derived from the triple-origin reassortant swine influenza viruses, and the rest of the internal genes from influenza A (H1N1) pdm09 virus.

• New findingsThis study investigated a case of the EAH1N1 SIV infection in a child. This is the first case of the EAH1N1 SIV genotype G4 infection in a child in Jiangsu Province. This virus maintained the genetic properties of the EAH1N1 SIV but differed significantly in HA protein antigens.

• Significance of the studyThis new human case of the EAH1N1 SIV infection indicates the pandemic potential of avian influenza viruses.


Abstract

Pigs are vital genetic mixing vessels for human and avian influenza viruses because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors. Cross-species transmission of influenza A viruses from swine to humans occurs occasionally. The first case of human infection with the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIVs) genotype G4 was detected in Jiangsu Province, China, in February 2023, and backtracking epidemiological investigations did not reveal a clear source of the infection. The hemagglutination (HA) and neuraminidase (NA) amino acid variant sites, antiviral drug susceptibility, and antigenic variation of the isolated A/Jiangsu/27271/2023 (JS/27271/23) virus were analyzed, and we evaluated the protective effect of sera collected from occupationally exposed populations in 2024 against the virus. Compared with the vaccine strain, the nucleotide sequence similarities of JS/27271/23 HA and NA were 96.5 % and 95.2 %, respectively. JS/27271/23 was sensitive to polymerase inhibitors (favipiravir and baloxavir), and the antigenicity of its HA protein was 8-fold different from that of the vaccine strain. The percentage of occupationally exposed population with antibody titers of ≥ 40 against A/Hunan/42443/2015 (HN/42443/15) and A/Jiangsu/1/2011 (JS/1/11) were 7.25 % and 2.25 %, respectively, and the geometric mean titers (GMT) were 6.24 and 5.34, respectively. Out of 400 serum samples examined, none had antibody titers of ≥ 40 against JS/27271/23. This suggests that low serum levels of antibodies to EAH1N1 SIVs in occupationally exposed populations may not provide adequate protection because of significant differences in amino acid sites and antigenicity between this virus and the current vaccine strain of EAH1N1 SIVs. There is no evidence of human-to-human transmission of EAH1N1 SIVs. Therefore, surveillance for EAH1N1 SIVs and the development of new vaccine strains are required.

Source: Biosafety and Health, https://www.sciencedirect.com/science/article/pii/S2590053624001381?via%3Dihub

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#MERS #coronavirus - Kingdom of #Saudi Arabia

Situation at a glance

This is the bi-annual update on the Middle East respiratory syndrome coronavirus (MERS-CoV) infections reported to the World Health Organization (WHO) from the Kingdom of Saudi Arabia (KSA). 

From 6 September 2024 to 28 February 2025, four laboratory-confirmed cases of MERS-CoV infection, including two deaths, were reported to WHO by the Ministry of Health of the KSA. 

One of the four cases was a secondary case exposed to the virus in a healthcare facility (nosocomial transmission). 

Close contacts of the four cases were followed up by the Ministry of Health. 

No additional secondary cases have been detected. 

The notification of these four cases does not alter the overall risk assessment, which remains moderate at both the global and regional levels. 

The reporting of these cases shows that the virus continues to pose a threat in countries where it is circulating in dromedary camels, particularly those in the Middle East.


Description of the situation

Between 6 September 2024 and 28 February 2025, the Ministry of Health (MoH) of the Kingdom of Saudi Arabia (KSA) reported four cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including two deaths, with the last case being reported on 4 February 2025. 

The cases were reported from the Hail (2), Riyadh (1) and the Eastern (1) Provinces of the KSA (...). 

Laboratory confirmation of the cases was performed by real-time polymerase chain reaction (RT-PCR) between 8 November 2024 and 4 February 2025.

All cases involved males aged between 27 and 78 years, and all presented with comorbidities. None were health workers, and from investigations only one was found to have indirect contact with dromedary camels (hosts of MERS-CoV) and their raw products (milk).

Two cases, with symptoms onset in November 2024, were identified within the same hospital. 

The first case was confirmed on 11 November through RT-PCR testing, and follow-up on close contacts revealed a secondary case that shared the same hospital room and developed symptoms subsequently. 

Neither of the two patients had direct or indirect contact with dromedary camels, including consumption of raw camel milk in the 14 days prior to the onset of symptoms.

Since the first report of MERS-CoV in KSA in 2012, a total 2618 laboratory-confirmed cases of MERS-CoV infection, with 945 associated deaths (CFR 36%), have been reported to WHO from 27 countries, across all six WHO regions. 

The majority of cases (2209; 84%), have been reported from KSA, including these newly reported cases. Since 2019, no MERS-CoV infections have been reported from countries outside the Middle East.

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Epidemiology

Middle East respiratory syndrome (MERS) is a respiratory illness caused by a coronavirus (MERS-CoV). The fatality rate among confirmed cases is around 36%, though this may be an overestimate since milder cases often go undetected. The case fatality ratio (CFR) is calculated based solely on laboratory-confirmed infections, which may not reflect the correct mortality rate.

Humans contract MERS-CoV through direct or indirect contact with dromedary camels, the virus’s natural host and zoonotic reservoir. While human-to-human transmission is possible, it has mainly occurred in close-contact situations, particularly in healthcare settings. Outside these environments, there has been limited human-to-human transmission to date.

MERS can present with no symptoms, mild respiratory issues, or severe illness leading to acute respiratory distress and death. Common symptoms include fever, cough, and breathing difficulties, with pneumonia frequently observed, though not always present. Some patients also experience gastrointestinal symptoms such as diarrhoea. Severe cases may require intensive care, including mechanical ventilation. Those at higher risk of severe outcomes include older adults, individuals with weakened immune systems, and those with chronic conditions like diabetes, kidney disease, cancer, or lung disorders.

The number of MERS-CoV infections reported to WHO has substantially declined since the beginning of the COVID-19 pandemic. Initially, this was likely the result of epidemiological surveillance activities for COVID-19 being prioritized. The similar clinical picture of both diseases may result in reduced testing and detection of MERS-CoV infections. In addition, measures taken to reduce SARS-CoV-2 transmission (e.g., mask-wearing, hand hygiene, physical distancing, improving the ventilation of indoor spaces, respiratory etiquette, stay-at-home orders, reduced mobility) also likely reduced opportunities for onward human-to-human transmission of MERS-CoV. Potential cross-protection conferred from infection with or vaccination against SARS-CoV-2 and any reduction in MERS-CoV infection or disease severity and vice versa has been hypothesized but requires further investigation.

No vaccine or specific treatment is currently available, although several MERS-CoV-specific vaccines and therapeutics are in development. Treatment remains supportive, focusing on managing symptoms based on the severity of the illness.


Public health response

Apart from the two cases linked to healthcare settings, the Ministry of Health did not detect any additional secondary infections. Triage for respiratory diseases has been implemented in the concerned hospital to enable early detection of patients with respiratory symptoms. In addition, comprehensive refresher training on the case definition has commenced for all health and care workers to ensure early detection of cases.


WHO risk assessment

The notification of these four additional cases does not change the overall risk assessment. WHO expects that additional cases of MERS-CoV infection will be reported from the Middle East and/or other countries where MERS-CoV is circulating in dromedaries, and that cases will continue to be exported to other countries by individuals who were exposed to the virus through contact with dromedaries or their products (consumption of raw camel milk), or in a healthcare setting. WHO continues to monitor the epidemiological situation and conducts risk assessment based on the latest available information.


WHO advice

Based on the current situation and available information, WHO re-emphasizes the importance of strong surveillance by all Member States for acute respiratory infections, including MERS-CoV, and to carefully review and investigate any unusual patterns.

Human-to-human transmission of MERS-CoV in health care settings has been associated with delays in recognizing the early symptoms of MERS-CoV infection, delayed triage of suspected cases, and delays in implementing infection prevention and control (IPC) measures. IPC measures are critical to prevent the possible spread of MERS-CoV between people in health care facilities. Health workers should consistently apply standard precautions, including risk assessment for any new onset of symptoms of respiratory infections, consistently with all patients, at every interaction in health-care settings.

Contact and droplet precautions, which include patient placement in single rooms with dedicated care equipment, and the use of personal protective equipment (PPE) such as clean non-sterile gown, gloves, eye protection and a well-fitting medical mask, should be added to standard precautions when providing care to patients with MERS-CoV. Ventilation rates in patient care rooms should meet or exceed 60 litres per second per patient (or 6 air changes per hour). Airborne precautions should be applied when performing aerosol-generating procedures or in settings where aerosol-generating procedures are conducted, including the use of procedure rooms with ventilation rates meeting or exceeding 160 litres per second (or 12 air changes per hour). Early identification, case management and isolation of cases, quarantine of contacts, together with appropriate IPC measures in health-care settings and public health awareness can prevent human-to-human transmission of MERS-CoV. 

MERS-CoV infection appears to cause more severe disease in people with underlying chronic medical conditions such as diabetes, renal failure, chronic lung disease, and in immunocompromised persons. Therefore, people with these underlying medical conditions should avoid close contact with animals, particularly dromedaries, when visiting farms, markets, or barn areas where the virus may be circulating. General hygiene measures should be adhered to, such as regular hand washing before and after touching animals and avoiding contact with sick animals. 

Food hygiene practices should be observed. People should avoid drinking raw camel milk, contact with camel urine or eating camel meat that has not been thoroughly cooked. The consumption of raw or undercooked animal products, including milk and meat, carries a high risk of infection from pathogens that may cause disease in humans. Animal products that are processed appropriately through cooking or pasteurization are safe for consumption. Foods that have gone through these processes should be handled with care to avoid cross contamination with uncooked/unsafe foods. Camel meat and camel milk are nutritious products that can continue to be consumed after cooking, pasteurization or other thermal treatments. 

WHO does not advise special screening at points of entry regarding this event, nor does it currently recommend the application of any travel or trade restrictions.

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Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON560

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#Marburg virus disease– United Republic of #Tanzania

Situation at a glance

On 13 March 2025, the Ministry of Health of the United Republic of Tanzania declared the end of the Marburg virus disease (MVD) outbreak. 

This declaration came after two consecutive incubation periods (a total of 42 days) since the last person confirmed with MVD died on 28 January 2025 and was given a safe and dignified burial, in accordance with WHO recommendations. 

No new confirmed cases were reported since then. 

The outbreak was declared on 20 January 2025. As of 12 March 2025, two confirmed and eight probable cases were reported by the Ministry of Health from Biharamulo district in Kagera region. All 10 cases died (case fatality ratio 100%), including eight who died before the confirmation of the outbreak. A total of 272 contacts that were listed for monitoring completed their 21-day follow-up as of 10 February 2025. WHO, through its country office, and partners provided technical, operational and financial support to the government to contain this outbreak. The risk of re-emergence of MVD remains after the official declaration of the end of the outbreak, linked to the animal reservoir’s presence in the country. WHO encourages maintaining early case detection and care capacities in addition to sustaining the ability to quickly respond, and continued risk communication and community engagement.


Description of the situation

Since the last Disease Outbreak News on this event, published on 14 February 2025, no new confirmed cases of Marburg virus disease (MVD) have been reported in the United Republic of Tanzania.

As of 12 March 2025, 10 cases have been reported including two confirmed and eight probable cases. All cases resulted in deaths, including eight who died before the confirmation of the outbreak and were classified as probable cases, resulting in a case fatality ratio of 100%.

The first identified case, an adult female, had symptom onset on 9 December and died on 16 December 2024. The last confirmed case died on 28 January, and a safe and dignified burial was performed. No new confirmed or probable cases have been reported following this burial. All 10 cases were reported from Biharamulo district in Kagera region; the median age of cases was 30 years (range: 1 to 75 years) and the majority of cases (70%, 7) were females.

Cumulatively, 108 suspected cases were reported between 20 January and 11 March, of which 106 tested negative for MVD.

As of 12 March 2025, 281 contacts had been listed, including nine who were subsequently classified as probable and confirmed cases and 272 contacts who completed 21 days of follow-up.

On 13 March 2025, after two consecutive incubation periods (a total of 42 days) without a new confirmed case being reported after the last confirmed case died on 28 January 2025, the Ministry of Health of the United Republic of Tanzania declared the end of the MVD outbreak, as per WHO recommendations.

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Epidemiology

MVD is a highly virulent disease that can cause severe disease and is clinically similar to Ebola disease (EBOD). EBOD and MVD are caused by orthoebolaviruses and orthomarburgviruses respectively; both are members of the Filoviridae family (filovirus). People become infected after prolonged exposure to mines or caves inhabited by Rousettus fruit bat colonies, a type of fruit bat that can carry the Marburg virus.  Marburg virus then spreads between people via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing) contaminated with these fluids. Health workers have previously been infected while treating patients with MVD. Burial ceremonies that involve direct contact with the body of the deceased can also contribute to the transmission of Marburg virus.

The incubation period varies from two to 21 days. Illness caused by the Marburg virus begins abruptly, with a high fever, severe headache, and severe malaise. Severe watery diarrhoea, abdominal pain and cramping, nausea, and vomiting can begin on the third day. Although not all cases present with haemorrhagic signs, severe haemorrhagic manifestations may appear between five and seven days from symptom onset, and fatal cases usually have some form of bleeding, often from multiple areas of the body. In fatal cases, death occurs most often between eight and nine days after symptom onset, usually preceded by severe blood loss and shock. There is currently no approved treatment or vaccine for MVD. Some candidate vaccines and therapeutics are currently under investigation.

Eighteen outbreaks of MVD have previously been reported globally. The most recent outbreak was reported in Rwanda between September and December 2024. Additional countries that previously reported outbreaks of MVD in the African Region include Angola, the Democratic Republic of the Congo, Equatorial Guinea, Ghana, Guinea, Kenya, South Africa, and Uganda. 


Public health response

The Ministry of Health developed a national response plan to guide response activities.

A National Incident Management System was activated to coordinate the response to the event; a national task force was activated, and meetings were held weekly. At the sub-national level, regular coordination meetings were held daily in Kagera Region.

A national rapid response team was deployed to Kagera to enhance outbreak investigation and response, with technical and operational support from WHO and health partners.

WHO deployed experts to support the Ministry of Health with Emergency management and partner coordination, clinical management, health logistics, infection prevention and control, and other response activities in different pillars.

Surveillance activities were conducted with active case finding, contact tracing and mortality surveillance across affected and neighbouring areas.

The mobile laboratory deployed in Kabyaile was utilized to support the testing of suspect cases for rapid turnaround time, and samples were referred to the National Public Health Laboratory in Dar es Salaam for additional tests.  

Travellers departing from the Kagera Region were screened at key points of entry and exit, including Bukoba airport.

Health and care worker sensitization sessions on infection prevention and control were conducted across Kagera and other regions.

The Marburg Treatment Unit was upgraded with enhanced triage, patient wards, and donning and doffing areas.

Public awareness campaigns were conducted, including health education, door-to-door outreach by community health workers, and public announcements in high-risk areas.

Cross-border meetings were convened between Tanzania, Uganda, and Burundi.

WHO procured and delivered four VHF kits to Kagera region to support care for patients and infection prevention and control measures.


WHO risk assessment

With two confirmed cases and eight probable cases reported, this is the second MVD outbreak reported in the country in the last three years. Both outbreaks occurred in the same region of Kagera located at the border with Rwanda and Uganda. 

The case fatality ratio of 100% is concerning, although has been recorded in previous outbreaks, additionally 8 of the 10 cases were probable i.e. reported after their death. Late health seeking behaviour in MVD outbreaks increases the risk of further transmission.  

The source of the outbreak is still unknown, and research activities are planned. Based on the outbreak investigation and surveillance activities during the response, which included contact tracing, alert management, active case search, and mortality surveillance, no additional cases have been reported during the 42-day countdown period. However, there remains a risk of re-emergence of MVD following the declaration of the end of the outbreak, linked to a new spillover from interactions with the animal reservoir.

Based on the available information at the end of MVD outbreak in Tanzania, the risk is considered as moderate at the national level, and low at regional and global levels.


WHO advice

WHO encourages maintaining early detection and care capacities in addition to sustaining the ability to quickly respond after the outbreak ends. This is to make sure that if the disease re-emerges, health authorities can detect it immediately, prevent the disease from spreading again, and ultimately save lives.

Raising awareness of risk factors for Marburg virus infection and protective measures that individuals can take is an effective way to reduce human transmission. WHO advises the following risk reduction measures as an effective way to reduce MVD transmission in healthcare facilities and in communities:

-- Reducing the risk of bat-to-human transmission arising from prolonged exposure to mines or caves inhabited by fruit bat colonies. People visiting or working in mines or caves inhabited by fruit bat colonies should wear gloves and other appropriate protective clothing (including masks).

-- Capabilities for early detection of MVD patients should be maintained over time in settings at risk of the disease.

-- Reducing the risk of human-to-human transmission in the community arising from direct or close contact with infected patients, particularly with their body fluids. Close physical contact with MVD patients should be avoided. Patients suspected or confirmed for MVD should be isolated in a designated treatment centre for early care and to avoid transmission at home.

-- Communities affected by MVD, along with health authorities, should ensure that the population is well informed, both about the nature of the disease itself and about necessary outbreak containment measures.

-- Outbreak containment measures include safe and dignified burial of the deceased, identifying people who may have been in contact with someone infected with MVD and monitoring their health for 21 days, separating the healthy from the sick to prevent further spread and providing care to the confirmed patient. Maintaining good hygiene and a clean environment need to be observed.

-- Critical infection prevention and control measures should be implemented and/or strengthened in all health care facilities, per WHO’s Infection prevention and control guideline for Ebola and Marburg disease. Health workers caring for patients with confirmed or suspected MVD should apply transmission-based precautions in addition to: standard precautions, including appropriate use of PPE and hand hygiene according to the WHO 5 moments to avoid contact with patient’s blood and other body fluids and with contaminated surfaces and objects. Waste generated in healthcare facilities must be safely segregated, collected, transported, stored, treated and finally disposed. Follow the national guidelines, rules and regulations for safe waste disposal or follow the WHO’s guidelines on safe waste management.

-- Patient-care activities should be undertaken in a clean and hygienic environment that facilitates practices related to the prevention and control of health-care-associated infections (HAIs) as outlined in Essential environmental health standards in health care. Safe water, adequate sanitation and hygiene infrastructure and services should be provided in healthcare facilities. For details on recommendations and improvement, follow the WASH FIT implementation Package

-- WHO encourages countries to implement a comprehensive care programme to support people who have recovered from MVD (if any) with any subsequent sequelae and to enable them to access body fluid testing and to mitigate the risk of transmission through infected body fluids by adequate practices.

Based on the current risk assessment, WHO advises against any travel and trade restrictions with the United Republic of Tanzania.

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Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON559

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A novel reassorted #swine #H3N2 #influenza virus demonstrates an undetected #human-to-swine #spillover in Latin #America and highlights zoonotic risks

Highlights

• First isolation and molecular evidence of the subtype H3N2 in swine in Colombia.

• Swine H3N2 discovered is phylogenetically divergent from other viruses.

• Colombian H3N2 was originated from an independent human-to-swine spillover.

• Sequence-based analysis reveals this is a novel antigenic variant.

• Due to antigenic variation, Colombian H3N2 possess a relevant zoonotic risk.


Abstract

Influenza A virus (FLUAV) affects a wide range of hosts, including humans and animals, posing a threat to public health. In swine, H3N2 subtype is associated with human-to-swine spillovers of seasonal viruses. In Latin America, the molecular and antigenic characteristics of swine FLUAV H3N2, as well as its phylogenetic origin, are poorly understood. Therefore, the objective of this study was to characterize the first swine H3N2 detected in Colombia. The origin and lineage of the virus were estimated through phylogenetic and molecular clock analyses. Antigenic characterization was achieved by comparing the amino acid constitution of the HA with previously reported swine FLUAVs and seasonal vaccine strains using a sequence-based method. In addition to HA and NA, internal genes were also characterized. The results showed that the Colombian H3N2 corresponded to a novel phylogenetic and antigenic swine FLUAV variant that emerged due to an independent reverse zoonotic event, likely occurring in Colombia in the early 2000s. The immunodominant epitope in the virus was predominantly present in antigenic epitope A, which showed the highest amino acid variation. Some mutations that alter the N-Glycosylation of antigenic sites at the HA were detected. Internally, the virus exhibited pandemic configuration. This study provides the first evidence of a novel FLUAV in Colombia and describes its origin, variability, and persistence in geographically restricted populations, highlighting the need for strengthen molecular surveillance of the virus in animal populations.

Source: Virology, https://www.sciencedirect.com/science/article/abs/pii/S0042682225000959?via%3Dihub

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#Evidence of novel #reassortment in clade 2.3.4.4b avian #influenza #H5N1 viruses, #India, 2024

Highlights

• This is the first report of clade 2.3.4.4b H5N1 virus from India.

• Evidence of novel reassortment between H5N1 and low pathogenic H3N8 viruses.

• Absence of H5N1 infection among people with probable exposure.


Abstract

H5N1 viruses belonging to clade 2.3.4.4b have caused unprecedented outbreaks globally. Outbreaks of H5N1 virus were reported in poultry and wild birds from Kerala (India) in the year 2024. Samples from birds and the environment were collected. Real-time RT-PCR and virus isolation using embryonated chicken eggs were carried out. Eight out of 20 samples were positive for virus isolation. The virus showed avian type receptor specificity using sialidase assay. Full genome sequencing revealed markers associated with high pathogenicity and mammalian adaptation. All the viruses belonged to a single genotype with multiple reassortments, including internal gene segments from an avian influenza (AI) H3N8 virus reported from Kerala. Surveillance among individuals with probable exposure showed absence of human infection. This is the first report of the genetic and virological characterization of clade 2.3.4.4b H5N1 viruses from India, highlighting the need for increased AI surveillance at the human-animal and domestic-wild bird interfaces.

Source: Virology, https://www.sciencedirect.com/science/article/abs/pii/S0042682225000947?via%3Dihub

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Wednesday, March 12, 2025

#HPAI Virus in #Mammals: Lack of #Detection in #Cattle With Respiratory Tract Infections & Genetic Analysis of Sporadic #Spillover Infections in Wild Mammals in #Bavaria, Germany, 2022–23

ABSTRACT

Background

In 2021, the H5N1 clade 2.3.4.4b Avian Influenza Viruses (AIVs) emerged on the American continent. At the same time, a further global spread took place. Infections have been reported in avian species as well as in over 50 mammalian species in 26 countries, and often result in severe disease with notable neurological pathology. Outbreaks in dairy cattle in the United States in 2024 illustrate viral transmission at a non-traditional interface and cross-species transmission. This development raises significant global concern regarding the virus's potential for wider spread. Given that H5N1 infections in birds reached record-high levels in Germany by late 2022, it is important to investigate whether Influenza A Virus (IAV) infections were also occurring in mammals sharing habitats with wild birds.

Methods and Results

Selected wild and domestic mammal populations were monitored over a two-year period (from January 2022 to December 2023), which coincided with a major infection period in wild birds in Bavaria. Genomes of Highly Pathogenic Avian IAV H5N1 (clade 2.3.4.4b) were detected in red foxes but not in samples from ruminants such as red deer or domestic cattle. Analyses of viral whole genome sequences revealed several mutations associated with mammalian adaptation.

Conclusion

Our results indicate a high frequency of spillover events to red foxes at a time when there was a peak of H5N1 infections in wild birds in Bavaria. Phylogenetic analyses show no specifically close genetic relationship between viruses detected in mammalian predators within a geographic area. While direct fox-to-fox transmission has not yet been reported, the H5N1 clade 2.3.4.4b AIVs' ability to spread through non-traditional interfaces and to cross species barriers underlines the importance of continuous IAV surveillance in mammals and possibly including previously unknown host species.

Source: Zoonoses and Public Health, https://onlinelibrary.wiley.com/doi/10.1111/zph.13217

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Highly Pathogenic Avian #Influenza A(#H5N1) Virus #Stability in Irradiated Raw #Milk and #Wastewater and on #Surfaces, #USA

Abstract

We measured stability of infectious influenza A(H5N1) virus in irradiated raw milk and wastewater and on surfaces. We found a relatively slow decay in milk, indicating that contaminated milk and fomites pose transmission risks. Although the risk is low, our results call for caution in milk handling and disposal from infected cattle.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/4/24-1615_article

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#Tecovirimat is #safe but #ineffective as #treatment for clade II #mpox

The antiviral drug tecovirimat used without other antivirals did not reduce the time to clinical resolution of clade II mpox lesions or improve pain control among adults in an international clinical trial sponsored by the National Institutes of Health (NIH). 

The trial enrollment was stopped in late 2024 when an interim analysis showed that tecovirimat monotherapy was ineffective in the study population. Detailed results were presented at the 2025 Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco.

“This study brought us a step forward in better understanding mpox disease and potential treatment strategies,” said Jeanne Marrazzo, M.D., M.P.H., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID), which sponsored and funded the trial. “We are grateful to the study team and participants for their contributions to groundbreaking research on a disease that we still do not know enough about.”

Mpox is caused by a virus that spreads mainly through close contact. Two types of the virus have been identified, referred to as clades I and II. A clade II virus subtype caused a global mpox outbreak in 2022, and the virus continues to circulate at low levels. In 2024, a clade I outbreak in Central and East African countries was declared a public health emergency of international concern. Travel-related cases of clade I mpox have been reported in the United States, but the risk of clade I mpox to the U.S. population remains low. People with significantly compromised immune systems or certain preexisting skin conditions, children and pregnant women have an elevated risk of developing severe mpox.

The Study of Tecovirimat for Mpox (STOMP) began in September 2022 as part of the U.S. whole-of-government response to the clade II mpox outbreak. There are no mpox treatments approved in the United States. Based on animal studies, tecovirimat, also known as TPOXX, was approved by the Food and Drug Administration (FDA) to treat smallpox(link is external)—a disease caused by a virus closely related to, but typically causing disease far more serious than, the virus that causes mpox. The drug had not been studied in people with mpox until the STOMP trial and a complementary study called PALM007 in the Democratic Republic of the Congo. PALM007 reported findings in 2024 that were similar to the findings reported from STOMP.

STOMP was a randomized international efficacy study that enrolled participants who had been ill with mpox for fewer than 14 days in Argentina, Brazil, Japan, Mexico, Peru, Thailand and the United States, including Puerto Rico. Randomized study participants and trial investigators were blinded, meaning they did not know who received tecovirimat or placebo. Children, pregnant women, study participants with certain skin conditions or substantially suppressed immune systems, and participants who had severe mpox disease as defined in the study protocol were assigned to an open-label study arm, meaning they all received tecovirimat instead of being randomized. The STOMP study assessed the safety of the drug among all study participants and, in randomized arms, evaluated whether a 14-day course of tecovirimat monotherapy reduced the time to clinical resolution of visible mpox lesions and improved other outcome measures like pain, compared to a placebo.

Randomized participants reported experiencing mpox symptoms for a median of eight days before study entry and had a median of nine mpox lesions. About a third of participants reported severe pain, selecting scores of 7-10 on an 11-point scale. By day 29 following study entry, an estimated 83% of participants receiving tecovirimat had reached clinical resolution, compared to 84% who received a placebo, a non-significant difference. Among those reporting severe pain at baseline, improvements were similar between those who received tecovirimat and placebo, with average pain scores decreasing by 3.2 points for participants receiving tecovirimat and by 3.1 points among those receiving the placebo. Participants’ lesions were swabbed and tested for the presence of DNA from the virus that causes mpox throughout the study. At day eight, 48% of participants receiving tecovirimat had undetectable viral DNA compared to 37% of participants receiving the placebo. The difference between the two arms narrowed by day 15 (82% for those receiving tecovirimat versus 80% for those receiving the placebo) as mpox resolved. These differences were not statistically significant at either time point. Adverse event rates were similar between both of the randomized study arms.

A separate exploratory analysis of data collected in STOMP’s open-label arm before the study had closed aimed to determine whether any factors were associated with faster mpox lesion resolution in participants with or at elevated risk of severe mpox. Faster clinical resolution was observed in participants who were younger in age or who did not have HIV or were living with HIV but virally suppressed on antiretroviral therapy; however, no association was significant when considering the duration of symptoms before study entry. The investigators noted that STOMP open-label participants had fewer lesions, but slower clinical resolution than reported from the PALM007 trial.

“Since the start of the clade II outbreak, clinicians treating mpox have had limited evidence to guide their practice, and STOMP provided definitive answers on the lack of clinical utility of tecovirimat monotherapy for the randomized population studied” said Timothy Wilkin, M.D., M.P.H., chief of the Division of Infectious Diseases and Global Public Health at the University of California, San Diego. “Taken together, these latest results also highlight that we still have yet to isolate which factors influence mpox disease progression and clinical resolution.”

The STOMP study was conducted by the NIH-funded ACTG, a global clinical trials network focused on HIV and other infectious diseases. SIGA Technologies, Inc., based in New York, provided tecovirimat for the study. Study results also will be published in a scientific journal.

For more information about STOMP, please visit ClinicalTrials.gov using the identifier NCT05534984.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Source: US National Institute of Health, https://www.nih.gov/news-events/news-releases/tecovirimat-safe-ineffective-treatment-clade-ii-mpox

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