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Public Health Nov 2023Most respiratory virus surveillance relies on medically attended respiratory illness, but an understanding of the true patterns of infection independent of care-seeking... (Observational Study)
Observational Study
OBJECTIVE
Most respiratory virus surveillance relies on medically attended respiratory illness, but an understanding of the true patterns of infection independent of care-seeking behaviour would enhance clinical and public health responses to respiratory virus outbreaks. We evaluated the potential of decedent surveillance by estimating the burden of respiratory virus infection in decedents in a large, urban medical examiner's office.
STUDY DESIGN
Observational.
METHODS
In 2020-2022, we tested nasopharyngeal swabs from 4121 decedents in Detroit, Michigan for 15 respiratory viruses, including SARS-CoV-2, respiratory syncytial virus, and influenza virus A and B. We analysed infection prevalence over time and by age, sex, race/ethnicity, and manner of death.
RESULTS
Of 4113 valid tests, 30.2% were positive for at least one virus, and 6.1% were positive for multiple viruses. All viruses were detected except for influenza A/H1N1 and influenza B. The most prevalent viruses were SARS-CoV-2 (15.7%), rhinovirus (11.2%), and adenovirus (4.9%), which were detected in all months. Most viruses exhibited decreasing prevalence with age, higher prevalence among Black and Hispanic than among White decedents and lower prevalence among deaths from natural causes; SARS-CoV-2 was a notable exception to the patterns by age and manner of death, instead reflecting community trends in catchment counties.
CONCLUSIONS
There was high prevalence and diversity of respiratory viruses in decedents entering a large, urban medical examiner's office. Decedent surveillance could offer a clearer picture of the true underlying burden of infection, motivating public health priorities for intervention and vaccine development, and augmenting data for real-time response to respiratory virus outbreaks.
Topics: Humans; Male; Female; Middle Aged; Respiratory Tract Infections; Adult; Michigan; Aged; Adolescent; Young Adult; Aged, 80 and over; Infant; Prevalence; Coroners and Medical Examiners; Urban Population; Child, Preschool; COVID-19; Child
PubMed: 37757630
DOI: 10.1016/j.puhe.2023.08.029 -
Enfermedades Infecciosas Y... Dec 2023Respiratory infection is the most common human adenovirus (HAdV) disease accounting for 7-8% of viral respiratory diseases in children less than 5 years. Differentiation...
INTRODUCTION
Respiratory infection is the most common human adenovirus (HAdV) disease accounting for 7-8% of viral respiratory diseases in children less than 5 years. Differentiation of bacterial infections and viral infections is a common clinical problem.
MATERIAL AND METHODS
One hundred oropharyngeal swabs obtained from October 2019 to November 2020 from patients attending the paediatric emergency room with suspicion of upper respiratory tract infection and negative results in influenza and RSV tests were included. Oropharyngeal swabs specimens were rapidly processed with STANDARD™ F Adeno Respi Ag FIA and the results were confirmed by RealStar® Adenovirus PCR Kit 1.0 (Altona diagnostics).
RESULTS
STANDARD™ F Adeno Respi Ag FIA had sensitivity and specificity values of 71.93% and 100% respectively. The performance of the test was higher in samples from children younger than 24 months and taken less than 72h since the beginning of symptoms. In this subgroup the test had 88.8% sensitivity and 100% specificity.
CONCLUSION
STANDARD™ F Adeno Respi Ag FIA may improve the management of respiratory diseases in children younger than 24 months and less than 72h since the beginning of symptoms in paediatric emergency rooms.
Topics: Humans; Child; Adenoviridae; Adenoviridae Infections; Respiratory Tract Infections; Polymerase Chain Reaction; Adenoviruses, Human
PubMed: 37076330
DOI: 10.1016/j.eimce.2022.09.015 -
Clinical Transplantation Nov 2023The gastrointestinal (GI) tract is a major human adenovirus (HAdV) replication site in patients undergoing hematopoietic stem cell transplantation (HSCT), yet the...
OBJECTIVES
The gastrointestinal (GI) tract is a major human adenovirus (HAdV) replication site in patients undergoing hematopoietic stem cell transplantation (HSCT), yet the prevalence and correlates of HAdV GI infection in this setting have remained poorly recognized, especially among adult HSCT recipients.
DESIGN OR METHODS
We retrospectively studied the prevalence and risk factors of HAdV GI-tissue infection in HSCT recipients (73 adults and 15 children) with GI symptoms who underwent GI-tissue biopsy between January-2012 and December-2017. The presence of HAdV in the GI tissues was determined by real-time PCR.
RESULTS
HAdV GI-tissue infection was detected in 21 (23.9%) patients, with similar infection rates identified in adults and children. GI-tissue detection was more common at late (>100 days) compared to early times post-transplantation (50% vs. 12.9%, p < .001). The presence of bloody diarrhea, Arab ethnicity (p = .014) and concurrent cytomegalovirus GI-tissue detection (p = .025) were significantly correlated with HAdV GI-tissue infection, while chronic graft versus host disease was of borderline association (p = .055).
CONCLUSIONS
Our findings reveal a high rate and new clinical-demographic correlates of HAdV GI-tissue infection in adult and pediatric HSCT recipients with GI symptoms. The findings highlight the need for future prospective studies to assess the relatedness of HAdV infection to the GI symptoms, and the prevalence, impact, and treatment of HAdV GI infection in HSCT recipients.
Topics: Adult; Humans; Child; Adenoviridae; Retrospective Studies; Prospective Studies; Adenoviridae Infections; Hematopoietic Stem Cell Transplantation; Adenovirus Infections, Human; Adenoviruses, Human; Biopsy
PubMed: 37563430
DOI: 10.1111/ctr.15098 -
Emerging Microbes & Infections Dec 2024Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe...
Re-emerging human adenovirus type 55 (HAdV55) has become a significant threat to public health due to its widespread circulation and the association with severe pneumonia, but an effective anti-HAdV55 agent remains unavailable. Herein, we report the generation of macaque-derived, human-like monoclonal antibodies (mAbs) protecting against HAdV55 infection with high potency. Using fluorophore-labelled HAdV55 virions as probes, we isolated specific memory B cells from rhesus macaques () that were immunized twice with an experimental vaccine based on E1-, E3-deleted, replication-incompetent HAdV55. We cloned a total of 19 neutralizing mAbs, nine of which showed half-maximal inhibitory concentrations below 1.0 ng/ml. These mAbs recognized the hyper-variable-region (HVR) 1, 2, or 7 of viral hexon protein, or the fibre knob. In transgenic mice expressing human desmoglein-2, the major cellular receptor for HAdV55, a single intraperitoneal injection with hexon-targeting mAbs efficiently prevented HAdV55 infection, and mAb 29C12 showed protection at a dose as low as 0.004 mg/kg. Fibre-targeting mAb 28E8, however, showed protection only at a dose up to 12.5 mg/kg. In tree shrews that are permissive for HAdV55 infection and disease, mAb 29C12 effectively prevented HAdV55-caused pneumonia. Further analysis revealed that fibre-targeting mAbs blocked the attachment of HAdV55 to host cells, whereas hexon-targeting mAbs, regardless of their targeting HVRs, mainly functioned at post-attachment stage via inhibiting viral endosomal escape. Our results indicate that hexon-targeting mAbs have great anti-HAdV55 activities and warrant pre-clinical and clinical evaluation.
Topics: Mice; Animals; Humans; Antibodies, Neutralizing; Mice, Transgenic; Antibodies, Viral; Adenoviruses, Human; Tupaia; Macaca mulatta; Antibodies, Monoclonal; Tupaiidae; Viral Proteins; Pneumonia
PubMed: 38240267
DOI: 10.1080/22221751.2024.2307513 -
International Journal of Molecular... Dec 2023Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1...
Cardiac hypertrophy resulting from sympathetic nervous system activation triggers the development of heart failure. The transcription factor Y-box binding protein 1 (YB-1) can interact with transcription factors involved in cardiac hypertrophy and may thereby interfere with the hypertrophy growth process. Therefore, the question arises as to whether YB-1 influences cardiomyocyte hypertrophy and might thereby influence the development of heart failure. YB-1 expression is downregulated in human heart biopsies of patients with ischemic cardiomyopathy ( = 8), leading to heart failure. To study the impact of reduced YB-1 in cardiac cells, we performed small interfering RNA (siRNA) experiments in H9C2 cells as well as in adult cardiomyocytes (CMs) of rats. The specificity of YB-1 siRNA was analyzed by a miRNA-like off-target prediction assay identifying potential genes. Testing three high-scoring genes by transfecting cardiac cells with YB-1 siRNA did not result in downregulation of these genes in contrast to , whose downregulation increased hypertrophic growth. Hypertrophic growth was mediated by PI3K under PE stimulation, as well by downregulation with YB-1 siRNA. On the other hand, overexpression of in CMs, caused by infection with an adenovirus encoding (AdYB-1), prevented hypertrophic growth under α-adrenergic stimulation with phenylephrine (PE), but not under stimulation with growth differentiation factor 15 (GDF15; = 10-16). An adenovirus encoding the green fluorescent protein (AdGFP) served as the control. overexpression enhanced the mRNA expression of the Gq inhibitor regulator of G-protein signaling 2 () under PE stimulation ( = 6), potentially explaining its inhibitory effect on PE-induced hypertrophic growth. This study shows that YB-1 protects cardiomyocytes against PE-induced hypertrophic growth. Like in human end-stage heart failure, YB-1 downregulation may cause the heart to lose its protection against hypertrophic stimuli and progress to heart failure. Therefore, the transcription factor YB-1 is a pivotal signaling molecule, providing perspectives for therapeutic approaches.
Topics: Adult; Humans; Animals; Rats; Adrenergic Agents; Phenylephrine; Heart Failure; Myocytes, Cardiac; RNA, Small Interfering; Adenoviridae; Cardiomegaly; Transcription Factors
PubMed: 38203580
DOI: 10.3390/ijms25010401 -
Cureus Nov 2023Background Measles is a highly contagious viral disease that has recently made headlines due to outbreaks in several parts of the world. The disease can cause serious...
Background Measles is a highly contagious viral disease that has recently made headlines due to outbreaks in several parts of the world. The disease can cause serious health complications, especially in young children, which has led to concerns about vaccination rates and public health policies. This study aims to investigate and describe the epidemiology, clinical characteristics, and outcomes of measles infection among children in Riyadh. Methodology We conducted a descriptive cross-sectional study among all pediatric patients with confirmed measles infection at a tertiary hospital from January 15, 2023, to March 15, 2023. We collected data including demographic characteristics, clinical presentations, and clinical outcomes. Results A total of 63 confirmed measles cases were reported. Most patients were under four years of age (82.7%), and 85.7% were unvaccinated. Adenovirus was the most common viral coinfection (12.7%). The most common complication was pneumonia (58.7%). Chest X-ray findings reported a localized right parenchymal infiltrate in 19% of patients and a patchy bilateral infiltrate in 15.9% of patients. In addition, 88.9% required hospital admission secondary to dehydration (47.6%) and hypoxia (41.3%). Among admitted patients, 17.5% were admitted to the pediatric intensive care unit (PICU), 9.5% were admitted due to respiratory failure, and 6.3% due to septic shock. Children under one year of age had a higher risk for PICU admission (p < 0.05). The mortality rate was 1.6%. Conclusions Measles is a serious disease that causes significant health effects and incurs high financial costs for public health systems. Vaccination remains the most effective way to prevent measles outbreaks and reduce their impact on individuals and communities.
PubMed: 38046773
DOI: 10.7759/cureus.48171 -
BioRxiv : the Preprint Server For... May 2024Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins...
UNLABELLED
Mammalian α-defensins are a family of abundant effector peptides of the mucosal innate immune system. Although primarily considered to be antimicrobial, α-defensins can increase rather than block infection by certain prominent bacterial and viral pathogens in cell culture and . We have shown previously that exposure of mouse and human adenoviruses (HAdVs) to α-defensins is able to overcome competitive inhibitors that block cell binding, leading us to hypothesize a defensin-mediated binding mechanism that is independent of known viral receptors. To test this hypothesis, we used genetic approaches to demonstrate that none of several primary receptors nor integrin co-receptors are needed for human α-defensin-mediated binding of HAdV to cells; however, infection remains integrin dependent. Thus, our studies have revealed a novel pathway for HAdV binding to cells that bypasses viral primary receptors. We speculate that this pathway functions in parallel with receptor-mediated entry and contributes to α-defensin-enhanced infection of susceptible cells. Remarkably, we also found that in the presence of α-defensins, HAdV tropism is expanded to non-susceptible cells, even when viruses are exposed to a mixture of both susceptible and non-susceptible cells. Therefore, we propose that in the presence of sufficient concentrations of α-defensins, such as in the lung or gut, integrin expression rather than primary receptor expression will dictate HAdV tropism . In summary, α-defensins may contribute to tissue tropism not only through the neutralization of susceptible viruses but also by allowing certain defensin-resistant viruses to bind to cells independently of previously described mechanisms.
AUTHOR SUMMARY
In this study, we demonstrate a novel mechanism for binding of human adenoviruses (HAdVs) to cells that is dependent upon interactions with α-defensin host defense peptides but is independent of known viral receptors and co-receptors. To block normal receptor-mediated HAdV infection, we made genetic changes to both host cells and HAdVs. Under these conditions, α-defensins restored cell binding; however, infection still required the function of HAdV integrin co-receptors. This was true for multiple types of HAdVs that use different primary receptors and for cells that are either naturally devoid of HAdV receptors or were engineered to be receptor deficient. These observations suggest that in the presence of concentrations of α-defensins that would be found naturally in the lung or intestine, there are two parallel pathways for HAdV binding to cells that converge on integrins for productive infection. Moreover, these binding pathways function independently, and both operate in mixed culture. Thus, we have found that viruses can co-opt host defense molecules to expand their tropism.
PubMed: 38854108
DOI: 10.1101/2024.05.30.596681 -
Infectious Disease Clinics of North... Sep 2023Pediatric solid organ transplant (SOT) recipients are at risk for infection following transplantation. Data from adult SOT recipients are often used to guide prevention... (Review)
Review
Pediatric solid organ transplant (SOT) recipients are at risk for infection following transplantation. Data from adult SOT recipients are often used to guide prevention and treatment of infections associated with organ transplantation in children. This article highlights key recent pediatric SOT-specific publications for an array of infectious complications of organ transplantation. Attention is given to areas of need for future study.
Topics: Child; Humans; Organ Transplantation; Transplant Recipients
PubMed: 37532391
DOI: 10.1016/j.idc.2023.06.002 -
Transplantation and Cellular Therapy Feb 2024Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical...
Post-transplantation cyclophosphamide (PTCy) is an effective strategy for graft-versus-host disease (GVHD) prophylaxis and is the standard of care for haploidentical hematopoietic cell transplantation (HCT). It is increasingly used for matched and mismatched unrelated donor (MUD/MMUD) HCT, but infections remain a concern. The objective of this study was to evaluate the characteristics and risk factors for infections in haploidentical and unrelated donor HCT recipients treated with PTCy-based GVHD prophylaxis. This single-center retrospective study examined 354 consecutive adults undergoing HCT with PTCy-based GVHD prophylaxis (161 MUD/MMUD; 193 haploidentical) between 2015 and 2022. Opportunistic infections (OIs), including cytomegalovirus (CMV), adenovirus (AdV), Epstein-Barr virus (EBV), and invasive fungal disease (IFD), were assessed from day 0 through day +365. The 1-year cumulative incidence functions of OIs and nonrelapse mortality (NRM) were calculated using dates of relapse and repeat HCT as competing risks. Secondary analysis evaluated risk factors for OIs and NRM using univariate and multivariable Cox regression models. Haploidentical HCT recipients had an increased risk of OIs compared to unrelated donor allograft recipients (39% for haploidentical versus 25% for MUD/MMUD; hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.16 to 2.49; P = .006). On multivariable analysis, haploidentical donor (HR, 1.50; 95% CI, 1.01 to 2.23; P = .046), prior HCT (HR, 1.99; 95% CI, 1.29 to 3.09; P = .002), and diagnosis of aGVHD (HR, 1.47; 95% CI, 1.02 to 2.14; P = .041) were associated with increased risk of OIs. NRM within the first year was not significantly different between the 2 cohorts (HR, 1.11; 95% CI, .64 to 1.93; P = .70). Overall, haploidentical donor was a significant risk factor for OIs in patients receiving PTCy, although 1-year NRM was not different between haploidentical HCT and MUD/MMUD HCT recipients. CMV and AdV infections were significantly increased among haploidentical HCT recipients, whereas the incidences of EBV infection and IFD were similar in the 2 cohorts. Our findings may have implications for infection monitoring and prophylaxis in the setting of PTCy, particularly in haploidentical HCT recipients.
Topics: Adult; Humans; Unrelated Donors; Retrospective Studies; Graft vs Host Disease; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Neoplasm Recurrence, Local; Cyclophosphamide; Allografts; Opportunistic Infections; Cytomegalovirus Infections
PubMed: 37984797
DOI: 10.1016/j.jtct.2023.11.015 -
Frontiers in Pediatrics 2023In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for... (Review)
Review
In April 2022, the World Health Organization (WHO) declared a global outbreak of acute hepatitis of unknown etiology (AHUE) with a high risk of severe outcomes, for which various etiologies have been proposed by the literature. This study examines primary reports of pediatric AHUE cases and summarizes the proposed etiologies. This systematic review collected and evaluated published peer-reviewed articles, official data, and clinical reports of AHUE cases that met the WHO working case definition. 19 hypothesized etiologies for AHUE were identified from 36 sources, which fell into eight categories. While human adenovirus (HAdV) infection, viral infection, and immune-mediated responses were commonly suspected as causes of AHUE, no definitive etiology or epidemiological link has been established. However, recent evidence implicates adeno-associated virus-2 (AAV2) as a likely significant contributor. Conducting a comprehensive literature review following outbreaks is necessary for developing responsive strategies and protocols.
PubMed: 38089685
DOI: 10.3389/fped.2023.1285348