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PLoS Neglected Tropical Diseases Jun 2024Ebolavirus disease (EVD) outbreaks have intermittently occurred since the first documented case in the 1970s. Due to its transmission characteristics, large outbreaks...
Ebolavirus disease (EVD) outbreaks have intermittently occurred since the first documented case in the 1970s. Due to its transmission characteristics, large outbreaks have not been observed outside Africa. However, within the continent, significant outbreaks have been attributed to factors such as endemic diseases with similar symptoms and inadequate medical infrastructure, which complicate timely diagnosis. In this study, we employed a stochastic modeling approach to analyze the spread of EVD during the early stages of an outbreak, with an emphasis on inherent risks. We developed a model that considers healthcare workers and unreported cases, and assessed the effect of non-pharmaceutical interventions (NPIs) using actual data. Our results indicate that the implementation of NPIs led to a decrease in the transmission rate and infectious period by 30% and 40% respectively, following the declaration of the outbreak. We also investigated the risks associated with delayed outbreak recognition. Our simulations suggest that, when accounting for NPIs and recognition delays, prompt detection could have resulted in a similar outbreak scale, with approximately 50% of the baseline NPIs effect. Finally, we discussed the potential effects of a vaccination strategy as a follow-up measure after the outbreak declaration. Our findings suggest that a vaccination strategy can reduce both the burden of NPIs and the scale of the outbreak.
Topics: Humans; Hemorrhagic Fever, Ebola; Disease Outbreaks; Vaccination; Stochastic Processes; Models, Statistical; Ebolavirus
PubMed: 38848434
DOI: 10.1371/journal.pntd.0011955 -
Human Vaccines & Immunotherapeutics Dec 2024A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups...
A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.
Topics: Humans; Female; Pregnancy; Respiratory Syncytial Virus Infections; United States; Adult; Respiratory Syncytial Virus Vaccines; Latent Class Analysis; Young Adult; Respiratory Syncytial Virus, Human; Infant; Surveys and Questionnaires; Patient Preference; Vaccination; Pregnant Women; Antibodies, Monoclonal; Adolescent
PubMed: 38847198
DOI: 10.1080/21645515.2024.2358566 -
Influenza and Other Respiratory Viruses Jun 2024In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory...
Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.
In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.
Topics: Humans; France; Respiratory Syncytial Virus Infections; Infant; Intensive Care Units, Pediatric; Case-Control Studies; Male; Female; Hospitalization; Respiratory Syncytial Virus, Human; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bronchiolitis; Bronchiolitis, Viral; Treatment Outcome
PubMed: 38840301
DOI: 10.1111/irv.13311 -
Respiratory Research Jun 2024The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology...
BACKGROUND
The concurrent circulation of SARS-CoV-2 with other respiratory viruses is unstoppable and represents a new diagnostic reality for clinicians and clinical microbiology laboratories. Multiplexed molecular testing on automated platforms that focus on the simultaneous detection of multiple respiratory viruses in a single tube is a useful approach for current and future diagnosis of respiratory infections in the clinical setting.
METHODS
Two time periods were included in the study: from February to April 2022, an early 2022 period, during the gradual lifting of COVID-19 prevention measures in the country, and from October 2022 to April 2023, the 2022/23 respiratory infections season. We analysed a total of 1,918 samples in the first period and 18,131 respiratory samples in the second period using a multiplex molecular assay for the simultaneous detection of Influenza A (Flu-A), Influenza B (Flu-B), Human Respiratory Syncytial Virus (HRSV) and SARS-CoV-2.
RESULTS
The results from early 2022 showed a strong dominance of SARS-CoV-2 infections with 1,267/1,918 (66.1%) cases. Flu-A was detected in 30/1,918 (1.6%) samples, HRSV in 14/1,918 (0.7%) samples, and Flu-B in 2/1,918 (0.1%) samples. Flu-A/SARS-CoV-2 co-detections were observed in 11/1,267 (0.9%) samples, and HRSV/SARS-CoV-2 co-detection in 5/1,267 (0.4%) samples. During the 2022/23 winter respiratory season, SARS-CoV-2 was detected in 1,738/18,131 (9.6%), Flu-A in 628/18,131 (3.5%), Flu-B in 106/18,131 (0.6%), and HRSV in 505/18,131 (2.8%) samples. Interestingly, co-detections were present to a similar extent as in early 2022.
CONCLUSION
The results show that the multiplex molecular approach is a valuable tool for the simultaneous laboratory diagnosis of SARS-CoV-2, Flu-A/B, and HRSV in hospitalized and outpatients. Infections with Flu-A/B, and HRSV occurred shortly after the COVID-19 control measures were lifted, so a strong reoccurrence of various respiratory infections and co-detections in the post COVID-19 period was to be expected.
Topics: Humans; COVID-19; Influenza B virus; Influenza, Human; SARS-CoV-2; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Influenza A virus; Male; Female; Coinfection; Middle Aged; Adult; Molecular Diagnostic Techniques; Seasons; Aged
PubMed: 38840154
DOI: 10.1186/s12931-024-02862-7 -
Pediatric Allergy and Immunology :... Jun 2024Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in infants. RSV bronchiolitis is associated with an increased risk of subsequent wheezing. We...
BACKGROUND
Respiratory Syncytial Virus (RSV) is the leading cause of hospitalization in infants. RSV bronchiolitis is associated with an increased risk of subsequent wheezing. We aimed to document the parents' perception of the link between RSV infection and subsequent wheezing, wheezing-related healthcare and family resources use, and its impact on family daily life.
METHODS
This cross-sectional online survey enrolled 1200 parents with at least one child ≤6y living in the United States, United Kingdom, Spain, and Italy. Children diagnosed with RSV bronchiolitis before age of 2 years were included in the RSV group, and those never diagnosed with RSV bronchiolitis in the Reference group.
RESULTS
The odds of wheezing were 4.5-fold (95%CI 3.5-5.9) higher in the RSV than in the Reference group. The odds increased to 7.7-fold (95%CI 5.4-11.1) among children who were hospitalized, and 9-fold (95%CI 5.1-16.6) among those admitted to pediatric intensive care with RSV bronchiolitis. Similar trends were observed across all countries. In total, 57% of parents reported their child's wheezing to have moderate to severe impact on their emotional well-being, and 53% on their daily life activities and/or social life. 64% of parents reported moderate-severe impact of wheezing on child's quality of sleep and 49% and 46% reported a moderate-severe impact on their children's emotional well-being and physical activities.
CONCLUSIONS
This survey suggests an association between RSV infection and subsequent wheezing in children across different countries. Wheezing, especially in association with RSV infection, was associated with increased healthcare utilization and costs, and significantly impacted parents' and children daily life.
Topics: Humans; Respiratory Sounds; Cross-Sectional Studies; Respiratory Syncytial Virus Infections; Parents; Male; Female; Infant; Child, Preschool; Italy; Surveys and Questionnaires; Spain; United Kingdom; United States; Hospitalization; Respiratory Syncytial Virus, Human; Adult; Child; Cost of Illness
PubMed: 38837464
DOI: 10.1111/pai.14169 -
Applied Microbiology and Biotechnology Jun 2024Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to...
Vacuum foam drying (VFD) has been shown to improve the thermostability and long-term shelf life of Newcastle Disease Virus (NDV). This study optimized the VFD process to improve the shelf life of NDV at laboratory-scale and then tested the optimized conditions at pilot-scale. The optimal NDV to T5 formulation ratio was determined to be 1:1 or 3:2. Using the 1:1 virus to formulation ratio, the optimal filling volumes were determined to be 13-17% of the vial capacity. The optimized VFD process conditions were determined to be at a shelf temperature of 25℃ with a minimum overall drying time of 44 h. The vaccine samples prepared using these optimized conditions at laboratory-scale exhibited virus titer losses of ≤ 1.0 log with residual moisture content (RMC) below 3%. Furthermore, these samples were transported for 97 days around China at ambient temperature without significant titer loss, thus demonstrating the thermostability of the NDV-VFD vaccine. Pilot-scale testing of the NDV-VFD vaccine at optimized conditions showed promising results for up-scaling the process as the RMC was below 3%. However, the virus titer loss was slightly above 1.0 log (approximately 1.1 log). Therefore, the NDV-VFD process requires further optimization at pilot scale to obtain a titer loss of ≤ 1.0 log. Results from this study provide important guidance for possible industrialization of NDV-VFD vaccine in the future. KEY POINTS: • The process optimization and scale-up test of thermostable NDV vaccine prepared through VFD is reported for the first time in this study. • The live attenuated NDV-VFD vaccine maintained thermostability for 97 days during long distance transportation in summer without cold chain conditions. • The optimized NDV-VFD vaccine preparations evaluated at pilot-scale maintained acceptable levels of infectivity after preservation at 37℃ for 90 days, which demonstrated the feasibility of the vaccine for industrialization.
Topics: Newcastle disease virus; Pilot Projects; Newcastle Disease; Viral Vaccines; Vacuum; Animals; Temperature; Chickens; Desiccation; China; Drug Stability; Viral Load
PubMed: 38836885
DOI: 10.1007/s00253-024-13174-7 -
Frontiers in Cellular and Infection... 2024The rabies virus enters the nervous system by interacting with several molecular targets on host cells to modify behavior and trigger receptor-mediated endocytosis of...
The rabies virus enters the nervous system by interacting with several molecular targets on host cells to modify behavior and trigger receptor-mediated endocytosis of the virion by poorly understood mechanisms. The rabies virus glycoprotein (RVG) interacts with the muscle acetylcholine receptor and the neuronal α4β2 subtype of the nicotinic acetylcholine receptor (nAChR) family by the putative neurotoxin-like motif. Given that the neurotoxin-like motif is highly homologous to the α7 nAChR subtype selective snake toxin α-bungarotoxin (αBTX), other nAChR subtypes are likely involved. The purpose of this study is to determine the activity of the RVG neurotoxin-like motif on nAChR subtypes that are expressed in brain regions involved in rabid animal behavior. nAChRs were expressed in oocytes, and two-electrode voltage clamp electrophysiology was used to collect concentration-response data to measure the functional effects. The RVG peptide preferentially and completely inhibits α7 nAChR ACh-induced currents by a competitive antagonist mechanism. Tested heteromeric nAChRs are also inhibited, but to a lesser extent than the α7 subtype. Residues of the RVG peptide with high sequence homology to αBTX and other neurotoxins were substituted with alanine. Altered RVG neurotoxin-like peptides showed that residues phenylalanine 192, arginine 196, and arginine 199 are important determinants of RVG peptide apparent potency on α7 nAChRs, while serine 195 is not. The evaluation of the rabies ectodomain reaffirmed the observations made with the RVG peptide, illustrating a significant inhibitory impact on α7 nAChR with potency in the nanomolar range. In a mammalian cell culture model of neurons, we confirm that the RVG peptide binds preferentially to cells expressing the α7 nAChR. Defining the activity of the RVG peptide on nAChRs expands our understanding of basic mechanisms in host-pathogen interactions that result in neurological disorders.
Topics: alpha7 Nicotinic Acetylcholine Receptor; Animals; Rabies virus; Humans; Xenopus laevis; Glycoproteins; Oocytes; Viral Proteins; Viral Envelope Proteins; Host-Pathogen Interactions; Protein Binding; Rabies; Acetylcholine; Neurotoxins
PubMed: 38836054
DOI: 10.3389/fcimb.2024.1394713 -
Mikrochimica Acta Jun 2024A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid...
A trendsetting direct competitive-based biosensing tool has been developed and implemented for the determination of the polyunsaturated fatty acid arachidonic acid (ARA), a highly significant biological regulator with decisive roles in viral infections. The designed methodology involves a competitive reaction between the target endogenous ARA and a biotin-ARA competitor for the recognition sites of anti-ARA antibodies covalently attached to the surface of carboxylic acid-coated magnetic microbeads (HOOC-MµBs), followed by the enzymatic label of the biotin-ARA residues with streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The resulting bioconjugates were magnetically trapped onto the sensing surface of disposable screen-printed carbon transducers (SPCEs) to monitor the extent of the biorecognition reaction through amperometry. The operational functioning of the exhaustively optimized and characterized immunosensing bioplatform was highly convenient for the quantitative determination of ARA in serum samples from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-) and respiratory syncytial virus (RSV)-infected individuals in a rapid, affordable, trustful, and sensitive manner.
Topics: Humans; Arachidonic Acid; COVID-19; Biosensing Techniques; SARS-CoV-2; Horseradish Peroxidase; Respiratory Syncytial Viruses; Immunoassay; Streptavidin; Biotin; Limit of Detection
PubMed: 38834823
DOI: 10.1007/s00604-024-06440-y -
Developmental and Comparative Immunology Sep 2024Interferon regulatory factors (IRFs) are transcription factors involved in immune responses, such as pathogen response regulation, immune cell growth, and...
Interferon regulatory factors (IRFs) are transcription factors involved in immune responses, such as pathogen response regulation, immune cell growth, and differentiation. IRFs are necessary for the synthesis of type I interferons through a signaling cascade when pathogen recognition receptors identify viral DNA or RNA. We discovered that irf3 is expressed in the early embryonic stages and in all immune organs of adult zebrafish. We demonstrated the antiviral immune mechanism of Irf3 against viral hemorrhagic septicemia virus (VHSV) using CRISPR/Cas9-mediated knockout zebrafish (irf3-KO). In this study, we used a truncated Irf3 protein, encoded by irf3 with a 10 bp deletion, for further investigation. Upon VHSV injection, irf3-KO zebrafish showed dose-dependent high and early mortality compared with zebrafish with the wild-type Irf3 protein (WT), confirming the antiviral activity of Irf3. Based on the results of expression analysis of downstream genes upon VHSV challenge, we inferred that Irf3 deficiency substantially affects the expression of ifnphi1 and ifnphi2. However, after 5 days post infection (dpi), ifnphi3 expression was not significantly altered in irf3-KO compared to that in WT, and irf7 transcription showed a considerable increase in irf3-KO after 5 dpi, indicating irf7's control over ifnphi3 expression. The significantly reduced expression of isg15, viperin, mxa, and mxb at 3 dpi also supported the effect of Irf3 deficiency on the antiviral activity in the early stage of infection. The higher mortality in irf3-KO zebrafish than in WT might be due to an increased inflammation and tissue damage that occurs in irf3-KO because of delayed immune response. Our results suggest that Irf3 plays a role in antiviral immunity of zebrafish by modulating critical immune signaling molecules and regulating antiviral immune genes.
Topics: Animals; Zebrafish; Interferon Regulatory Factor-3; CRISPR-Cas Systems; Novirhabdovirus; Zebrafish Proteins; Gene Knockout Techniques; Hemorrhagic Septicemia, Viral; Animals, Genetically Modified; Fish Diseases; Immunity, Innate; Signal Transduction; Rhabdoviridae Infections; Disease Models, Animal; Interferons
PubMed: 38834141
DOI: 10.1016/j.dci.2024.105208 -
Journal of Medical Virology Jun 2024This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory...
This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory infections during 2015-2021 and assessed the impact of the coronavirus disease 2019 pandemic on hMPV infection. A single-center, retrospective cohort study was performed, including pediatric and adult patients with laboratory-confirmed hMPV. Of a total of 990 patients, 253 (25.6%), 105 (10.6%), 121 (12.2%), and 511 (51.6%) belonged to age groups 0-2, 3-17, 18-59, and ≥60 years, respectively. The highest percentage (23.0%) of patients were hospitalized during 2019 and the lowest (4.7%) during 2020. Patients < 18 years experienced high rates of comorbidities (immunodeficiencies: 14.4% and malignancies: 29.9%). Here, 37/39 (94.9%) of all bronchiolitis cases were diagnosed in patients < 2 years, whereas more patients in older age groups were diagnosed with pneumonia. A greater proportion of hMPV patients diagnosed with viral coinfection (mostly respiratory syncytial virus and adenovirus) were <18 years. The highest percentages of intensive care unit admissions were recorded among patients < 18 years. Our findings demonstrate that hMPV is an important cause of morbidity in young children and a possibly underestimated cause of morbidity among older adults.
Topics: Humans; Retrospective Studies; Metapneumovirus; Paramyxoviridae Infections; Israel; Middle Aged; Child; Male; Adult; Female; Infant; Adolescent; Child, Preschool; Hospitalization; Young Adult; COVID-19; Aged; Coinfection; Infant, Newborn; Respiratory Tract Infections; Comorbidity; Aged, 80 and over; SARS-CoV-2
PubMed: 38828947
DOI: 10.1002/jmv.29709