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Vaccines Jan 2024Four mutants varying the length of the G and SH genes, including a G-truncated mutant (ΔG) and three G/SH-truncated mutants (ΔSH/G-1, ΔSH/G-2, and ΔSH/G-3), were...
Four mutants varying the length of the G and SH genes, including a G-truncated mutant (ΔG) and three G/SH-truncated mutants (ΔSH/G-1, ΔSH/G-2, and ΔSH/G-3), were generated via serially passaging the avian metapneumovirus strain SNU21004 into the cell lines Vero E6 and DF-1 and into embryonated chicken eggs. The mutant ΔG particles resembled parental virus particles except for the variance in the density of their surface projections. G and G/SH truncation significantly affected the viral replication in chickens' tracheal ring culture and in infected chickens but not in the Vero E6 cells. In experimentally infected chickens, mutant ΔG resulted in the restriction of viral replication and the attenuation of the virulence. The mutants ΔG and ΔSH/G-1 upregulated three interleukins (IL-6, IL-12, and IL-18) and three interferons (IFNα, IFNβ, and IFNγ) in infected chickens. In addition, the expression levels of innate immunity-related genes such as , I, and , in BALB/c mice were also upregulated when compared to the parental virus. Immunologically, the mutant ΔG induced a strong, delayed humoral immune response, while the mutant ΔSH/G-1 induced no humoral immune response. Our findings indicate the potential of the mutant ΔG but not the mutant ΔSH/G-1 as a live attenuated vaccine candidate.
PubMed: 38276678
DOI: 10.3390/vaccines12010106 -
Frontiers in Public Health 2023Worldwide, the COVID-19 pandemic caused by SARS-CoV-2 has enormously impacted healthcare systems, especially in low and middle-income countries. Coinfections with...
Worldwide, the COVID-19 pandemic caused by SARS-CoV-2 has enormously impacted healthcare systems, especially in low and middle-income countries. Coinfections with respiratory pathogens in COVID-19 patients may contribute to worse outcomes. This study identified the presence of 12 viral coinfections and pneumococcal carriers among individuals with SARS-CoV-2 infection in outpatient and community settings in Ecuador. From January 2020 to November 2021, 215 nasopharyngeal and nasal swabs were taken from individuals who reported symptoms of COVID-19 or had known exposure to someone with confirmed or suspected COVID-19. One hundred fifty-eight tested positive for SARS-CoV-2 by RT-qPCR and coinfections were detected in 12% (19/158) of SARS-CoV-2-positive patients; the most frequent coinfection was with influenza A virus at 4.4% (7/158; 95% CI: 1.2-7.6), followed by respiratory syncytial virus with 3.1% (5/158; 95% CI: 0.4-5.8), and finally rhinovirus and human coronavirus NL63 with 1.2% (2/158). Pneumococcal carriage was detected in 3.7% (6/158; 95% CI: 0.76-6.64) of SARS-CoV-2 cases. Influenza B, adenovirus, human metapneumovirus (HMPV), parainfluenza virus types 1, 2, and 3, and human coronavirus HKU1 were undetected. To our knowledge, this is the first study of coinfection of SARS-CoV-2 and respiratory pathogens performed on outpatients in Latin America. The high proportion of outpatients with viral coinfections reported in our cohort allows us to suggest that testing for SARS-CoV-2 and other common respiratory pathogens should be carried out to ensure accurate diagnoses, prompt patient treatment, and appropriate isolation.
Topics: Humans; SARS-CoV-2; COVID-19; Outpatients; Coinfection; Pandemics; Ecuador
PubMed: 37965509
DOI: 10.3389/fpubh.2023.1264632 -
Archives of Disease in Childhood Nov 2023To describe the characteristics, differential diagnoses, management and outcomes of severe encephalitis in children.
OBJECTIVE
To describe the characteristics, differential diagnoses, management and outcomes of severe encephalitis in children.
DESIGN
A 10-year retrospective cohort study in children admitted to a tertiary paediatric intensive care unit (PICU) with suspected encephalitis. One to 6 months' follow-up data were compared between different categories.
PARTICIPANTS
Patients from 0 to 17 years of age with acute encephalopathy and one or more of fever, seizure, focal neurological findings, cerebrospinal fluid abnormalities, EEG/neuroimaging consistent with encephalitis.
MAIN OUTCOME MEASURES
Epidemiology, clinical features, outcomes and risk factor analysis.
RESULTS
175 children with encephalitis required intensive care unit (ICU) admission over 10 years. The median age was 4.5 months (IQR 1.6-54.8). The leading cause was enterovirus (n=49, 28%), followed by parechovirus, influenza, herpes simplex virus (HSV), human herpesvirus-6 (HHV-6), , acute-disseminated encephalomyelitis and anti-N-methyl-D-aspartate-receptor-associated encephalitis. Immune-mediated encephalitis had higher prevalence in females, older age and longer duration of encephalopathy. Mechanical ventilation was required by 74 children (42%); haemodynamic support by 28 children (16%), 3 received extracorporeal membrane oxygenation (ECMO) support. Eleven patients died (case fatality rate 6.3%): five with HHV-6, two enterovirus, two influenza, one HSV, one human-metapneumovirus. At follow-up, 34 children had mild or moderate disability, and six severe disability. In a multivariable logistic regression model, three factors were associated with severe disability or death: age <2 years old (OR 8.2, CI 1.0 to 67.2), Herpesviridae aetiology (OR 14.5, CI 1.2 to 177.3) and length of intubation (OR 1.005, CI 1.00 to 1.01).
CONCLUSIONS
Encephalitis has a varied aetiology and causes death or severe disability in 1 in every 10 children requiring intensive care.
Topics: Child; Female; Humans; Infant; Child, Preschool; Influenza, Human; Retrospective Studies; Encephalitis; Intensive Care Units, Pediatric; Enterovirus Infections; Enterovirus; Brain Diseases
PubMed: 37487693
DOI: 10.1136/archdischild-2023-325305 -
Frontiers in Pediatrics 2023Respiratory viruses might influence nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative...
BACKGROUND
Respiratory viruses might influence nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative nasal carriage density in a household setting before and during the COVID-19 pandemic.
METHODS
From November 2019-June 2021, we enrolled participants in a remote household surveillance study of respiratory pathogens. Participants submitted weekly reports of acute respiratory illness (ARI) symptoms. Mid-turbinate or anterior nasal swabs were self-collected at enrollment, when ARI occurred, and, in the second year of the study only, from household contacts after SARS-CoV-2 was detected in a household member. Specimens were tested using multiplex reverse-transcription PCR for respiratory pathogens, including , rhinovirus, adenovirus, common human coronavirus, influenza A/B virus, respiratory syncytial virus (RSV) A/B, human metapneumovirus, enterovirus, and human parainfluenza virus. We estimated differences in semiquantitative nasal carriage density, estimated by the inverse of relative cycle threshold (Crt) values, with and without viral detection for any virus and for specific respiratory viruses using linear generalized estimating equations of Crt values on virus detection adjusted for age and swab type and accounting for clustering of swabs within households.
RESULTS
We collected 346 swabs from 239 individuals in 151 households that tested positive for ( = 157 with and 189 without ≥1 viruses co-detected). Difficulty breathing, cough, and runny nose were more commonly reported among individuals with specimens with viral co-detection compared to without (15%, 80% and 93% vs. 8%, 57%, and 51%, respectively) and ear pain and headache were less commonly reported (3% and 26% vs. 16% and 41%, respectively). For specific viruses among all ages, semiquantitative nasal carriage density was greater with viral co-detection for enterovirus, RSV A/B, adenovirus, rhinovirus, and common human coronavirus ( < 0.01 for each). When stratified by age, semiquantitative nasal carriage density was significantly greater with viral co-detection among children aged <5 ( = 0.002) and 5-17 years ( = 0.005), but not among adults aged 18-64 years ( = 0.29).
CONCLUSION
Detection of common respiratory viruses was associated with greater concurrent semiquantitative nasal carriage density in a household setting among children, but not adults.
PubMed: 37484765
DOI: 10.3389/fped.2023.1198278 -
The Journal of Infectious Diseases Mar 2024In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract...
BACKGROUND
In addition to preventing pneumococcal disease, emerging evidence indicates that pneumococcal conjugate vaccines (PCVs) might indirectly reduce viral respiratory tract infections (RTI) by affecting pneumococcal-viral interactions.
METHODS
We performed a systematic review of interventional and observational studies published during 2000-2022 on vaccine efficacy/adjusted effectiveness (VE) and overall effect of PCV7, PCV9, PCV10, or PCV13 against viral RTI.
RESULTS
Sixteen of 1671 records identified were included. Thirteen publications described effects of PCVs against viral RTIs in children. VE against influenza ranged between 41-86% (n=4), except for the 2010-2011 influenza season. In a randomized controlled trial, PCV9 displayed efficacy against any viral RTI, human seasonal coronavirus, parainfluenza, and human metapneumovirus. Data in adults were limited (n=3). PCV13 VE ranged between 4-25% against viral lower RTI, 32-35% against COVID-19 outcomes, 24-51% against human seasonal coronavirus, and 13-36% against influenza A lower RTI, with some 95%CI spanning zero. No protection was found against adenovirus or rhinovirus in children or adults.
CONCLUSIONS
PCVs were associated with protection against some viral RTI, with the strongest evidence for influenza in children. Limited evidence for adults was generally consistent with pediatric data. Restricting public health evaluations to confirmed pneumococcal outcomes may underestimate the full impact of PCVs.
PubMed: 38462672
DOI: 10.1093/infdis/jiae125 -
ERJ Open Research Jan 2024The association between early-life lower respiratory tract infection (LRTI) and asthma is well established. Knowledge about bronchial hyperresponsiveness (BHR) and...
BACKGROUND
The association between early-life lower respiratory tract infection (LRTI) and asthma is well established. Knowledge about bronchial hyperresponsiveness (BHR) and asthma after metapneumovirus (MPV) LRTI is scarce. The aim of this study was to assess BHR and current asthma in school-aged children after hospital admission for early-life LRTI with MPV, and to compare with more well-known viruses, rhinovirus (RV) and respiratory syncytial virus (RSV), and with controls.
METHODS
A cohort consisting of children admitted for LRTI and controls was followed-up at school age with a clinical research assessment and lung function tests, including a methacholine provocation test. Current asthma was defined based on objective variable airway obstruction and clinical symptoms. BHR and asthma were compared according to viral groups.
RESULTS
135 children (median age 9.3 years) were included (16 MPV, 34 RV, 51 RSV, 13 mixed infections and 21 controls). Compared with controls there was increased BHR after MPV and RV LRTI (provocative dose causing a 20% fall in forced expiratory volume in 1 s and dose-response slope; p<0.05). Using Kaplan-Meier statistics, BHR was increased for MPV compared with both controls and RSV (p=0.02 and p=0.01). The proportion of children with current asthma at follow-up was higher in the LRTI children compared with the controls (46% versus 24%; p=0.06). Among children who had undergone MPV and RV infection, 50% fulfilled the asthma criteria compared with 43% in the RSV group (p=0.37).
CONCLUSION
We found increased BHR and a high prevalence of asthma in school-aged children after early-life MPV infection, and findings were similar to RV, and less to RSV, compared with controls.
PubMed: 38259817
DOI: 10.1183/23120541.00832-2023 -
Pediatric Pulmonology May 2024Bronchiolitis is a common lower respiratory tract infection (LRTI) affecting infants and young children. Respiratory syncytial virus (RSV) has historically been the... (Comparative Study)
Comparative Study
BACKGROUND
Bronchiolitis is a common lower respiratory tract infection (LRTI) affecting infants and young children. Respiratory syncytial virus (RSV) has historically been the primary causative agent, but other viruses also contribute to the LRTI epidemiology. Recent changes in epidemiology and clinical patterns due to the coronavirus disease 2019 (COVID-19) pandemic have raised concerns. This study aims to analyze the impact of the pandemic on bronchiolitis epidemiology and severity.
METHODS
Two consecutive bronchiolitis seasons (October 2021 to March 2022 and October 2022 to March 2023) were compared. Data on viral agents, hospitalization duration, clinical severity, and respiratory support requirements were collected from pediatric patients at San Marco Hospital, University of Catania.
RESULTS
In the 2021-2022 season, RSV was the predominant virus (40%), followed by other viruses, with mild clinical outcomes. In the 2022-2023 season, RSV remained prevalent (58.7%), but other viruses, including rhinovirus (RV) and influenza, showed a significant increase (p < .05) in bronchiolitis cases and severity. Notably, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season, contrary to the previous year.
CONCLUSION
The COVID-19 pandemic appears to have shifted the epidemiological landscape of bronchiolitis, with a peak incidence in November instead of January/February. Non-RSV viruses (RV, influenza A and B, as well as metapneumovirus) have gained prominence, possibly due to viral competition and reduced pandemic-related restrictions. Traditionally, RSV has been the primary pathogen responsible for most bronchiolitis cases. Nonetheless, the findings of this study indicate a shifting landscape in bronchiolitis etiology, with RSV gradually diminishing in its role. Contrary to the previous year, RSV-related bronchiolitis did not exhibit greater severity compared to non-RSV cases in the 2022-2023 season.
Topics: Humans; COVID-19; Infant; Male; Female; Bronchiolitis; Seasons; Hospitalization; SARS-CoV-2; Italy; Respiratory Syncytial Virus Infections; Severity of Illness Index; Child, Preschool; Infant, Newborn; Bronchiolitis, Viral
PubMed: 38353390
DOI: 10.1002/ppul.26904 -
Scientific Reports Apr 2024The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are...
The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are responsible for severe respiratory tract infections in infants, young children, elderly individuals, adults with chronic medical conditions, and immunocompromised patients. Despite their large impact on human health, vaccines for hRSV were only recently introduced, and only limited treatment options exist. Here we show that Ginkgolic acid (GA), a natural compound from the extract of Ginkgo biloba, with known antiviral properties for several viruses, efficiently inhibits these viruses' infectivity and spread in cultures in a dose-dependent manner. We demonstrate that the drug specifically affects the entry step during the early stages on the viruses' life cycle with no effect on post-entry and late stage events, including viral gene transcription, genome replication, assembly and particles release. We provide evidence that GA acts as an efficient antiviral for members of the Pneumoviridae family and has the potential to be used to treat acute infections.
Topics: Child; Adult; Infant; Humans; Child, Preschool; Aged; Paramyxoviridae Infections; Metapneumovirus; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Virus Diseases; Respiratory Syncytial Virus Infections; Antiviral Agents; Salicylates
PubMed: 38589437
DOI: 10.1038/s41598-024-58032-8 -
Influenza and Other Respiratory Viruses May 2024Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness...
BACKGROUND
Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs).
METHODS
HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results.
RESULTS
Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms.
CONCLUSIONS
These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.
Topics: Humans; Metapneumovirus; Male; Female; Severity of Illness Index; Respiratory Tract Infections; Middle Aged; Respiratory Syncytial Virus Infections; Influenza, Human; Hospitalization; Adult; Paramyxoviridae Infections; Aged; Young Adult; Respiratory Syncytial Virus, Human; Aged, 80 and over; Adolescent
PubMed: 38692663
DOI: 10.1111/irv.13275 -
Microorganisms Dec 2023Brazil is the second largest producer of broiler chicken in the world, and the surveillance of avian pathogens is of great importance for the global economy and...
Brazil is the second largest producer of broiler chicken in the world, and the surveillance of avian pathogens is of great importance for the global economy and nutrition. Avian metapneumovirus (aMPV) infection results in high rates of animal carcass losses due to aerosacculitis and these impacts can be worsened through co-infection with pathogenic bacteria, particularly (APEC). The present study evaluated the seroprevalence of the main aMPV subtypes in unvaccinated broiler chickens from poultry farms in Brazil, as well as the clinical effects of co-infection with APEC. Blood samples, respiratory swabs, femurs, liver, and spleen of post-mortem broiler chickens were collected from 100 poultry production batches, totaling 1000 samples. The selection of the production batch was based on the history of systemic and respiratory clinical signs. The results indicated that 20% of the lots showed serological evidence of the presence of aMPV, with two lots being positive for aMPV-B. A total of 45% of batches demonstrated co-infection between aMPV and APEC. The results point to the need for viral surveillance, targeted vaccination, and vaccination programs, which could reduce clinical problems and consequently reduce the use of antibiotics to treat bacterial co-infections.
PubMed: 38257889
DOI: 10.3390/microorganisms12010056