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BMC Medical Genomics Feb 2024We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children.
BACKGROUND
We aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children.
METHODS
The peripheral blood of five bacterial meningitis patients, five viral meningitis samples, and five healthy individuals were collected for RNA sequencing. Then, the differentially expressed lncRNA and mRNA were detected in bacterial meningitis vs. controls, viral meningitis vs. healthy samples, and bacterial vs. viral meningitis patients. Besides, co-expression and the competing endogenous RNA (ceRNA) networks were constructed. Receiver operating characteristic curve (ROC) analysis was performed.
RESULTS
Compared with the control group, 2 lncRNAs and 32 mRNAs were identified in bacterial meningitis patients, and 115 lncRNAs and 54 mRNAs were detected in viral meningitis. Compared with bacterial meningitis, 165 lncRNAs and 765 mRNAs were identified in viral meningitis. 2 lncRNAs and 31 mRNAs were specific to bacterial meningitis, and 115 lncRNAs and 53 mRNAs were specific to viral meningitis. The function enrichment results indicated that these mRNAs were involved in innate immune response, inflammatory response, and immune system process. A total of 8 and 1401 co-expression relationships were respectively found in bacterial and viral meningitis groups. The ceRNA networks contained 1 lncRNA-mRNA pair and 4 miRNA-mRNA pairs in viral meningitis group. GPR68 and KIF5C, identified in bacterial meningitis co-expression analysis, had an area under the curve (AUC) of 1.00, while the AUC of OR52K2 and CCR5 is 0.883 and 0.698, respectively.
CONCLUSIONS
Our research is the first to profile the lncRNAs in bacterial and viral meningitis in children and may provide new insight into understanding meningitis regulatory mechanisms.
Topics: Child; Humans; RNA, Long Noncoding; Gene Regulatory Networks; MicroRNAs; RNA, Messenger; RNA, Competitive Endogenous; Sequence Analysis, RNA; Meningitis, Bacterial; Meningitis, Viral; Receptors, G-Protein-Coupled; Kinesins
PubMed: 38347610
DOI: 10.1186/s12920-024-01820-y -
BMC Veterinary Research Dec 2023Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific...
Detection and disease diagnosis trends (2017-2022) for Streptococcus suis, Glaesserella parasuis, Mycoplasma hyorhinis, Actinobacillus suis and Mycoplasma hyosynoviae at Iowa State University Veterinary Diagnostic Laboratory.
BACKGROUND
Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific antemortem diagnostic tests, and the polymicrobial nature of swine diagnostic cases. The main objective of this retrospective study was to estimate temporal patterns of agent detection and disease diagnosis for five endemic bacteria that can cause systemic disease in porcine tissue specimens submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) from 2017 to 2022. The study also explored the diagnostic value of specific tissue specimens for disease diagnosis, estimated the frequency of polymicrobial diagnosis, and evaluated the association between phase of pig production and disease diagnosis.
RESULTS
S. suis and G. parasuis bronchopneumonia increased on average 6 and 4.3%, while S. suis endocarditis increased by 23% per year, respectively. M. hyorhinis and A. suis associated serositis increased yearly by 4.2 and 12.8%, respectively. A significant upward trend in M. hyorhinis arthritis cases was also observed. In contrast, M. hyosynoviae arthritis cases decreased by 33% average/year. Investigation into the diagnostic value of tissues showed that lungs were the most frequently submitted sample, However, the use of lung for systemic disease diagnosis requires caution due to the commensal nature of these agents in the respiratory system, compared to systemic sites that diagnosticians typically target. This study also explored associations between phase of production and specific diseases caused by each agent, showcasing the role of S. suis arthritis in suckling pigs, meningitis in early nursery and endocarditis in growing pigs, and the role of G. parasuis, A. suis, M. hyorhinis and M. hyosynoviae disease mainly in post-weaning phases. Finally, this study highlighted the high frequency of co-detection and -disease diagnosis with other infectious etiologies, such as PRRSV and IAV, demonstrating that to minimize the health impact of these endemic bacterial agents it is imperative to establish effective viral control programs.
CONCLUSIONS
Results from this retrospective study demonstrated significant increases in disease diagnosis for S. suis, G. parasuis, M. hyorhinis, and A. suis, and a significant decrease in detection and disease diagnosis of M. hyosynoviae. High frequencies of interactions between these endemic agents and with viral pathogens was also demonstrated. Consequently, improved control programs are needed to mitigate the adverse effect of these endemic bacterial agents on swine health and wellbeing. This includes improving diagnostic procedures, developing more effective vaccine products, fine-tuning antimicrobial approaches, and managing viral co-infections.
Topics: Humans; Swine; Animals; Mycoplasma hyorhinis; Mycoplasma hyosynoviae; Streptococcus suis; Actinobacillus suis; Mycoplasma Infections; Iowa; Retrospective Studies; Universities; Swine Diseases; Arthritis; Endocarditis
PubMed: 38087358
DOI: 10.1186/s12917-023-03807-w -
BMC Veterinary Research Oct 2023Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head...
BACKGROUND
Thirty-two-day-old broiler chickens at a farm located in northwestern South Korea displayed adverse neurological symptoms including limping, lying down, and head shaking. Approximately 2.1% of chickens died or were culled due to severe symptoms. Five carcasses were submitted to the Avian Disease Division of the Animal and Plant Quarantine Agency (APQA) for disease diagnosis.
RESULTS
Broilers displayed severe pericarditis and perihepatitis associated with gross lesions. Broilers also displayed microscopic lesions in the cerebrum and in the granular layer of the cerebellum, which were associated with multifocal perivascular cuffing and purulent necrosis in the cerebrum, and severe meningitis with heterophil and lymphocyte infiltration. Staphylococcus spp. were identified in the liver and heart using bacteriological culture. PCR/RT-PCR assays revealed that broilers were negative for avian Clostridium botulinum, Newcastle disease virus, and avian encephalomyelitis virus. Bacterial and viral metagenomic analysis of brain sample further revealed the presence of Pseudomonas spp. and Marek's disease virus, which are known etiological agents of chicken meningoencephalitis.
CONCLUSIONS
This study reports a diagnostic analysis of gross and histopathological lesions from 32-day-old broilers displaying unique neurological symptoms that revealed the presence of the several neurological diseases including meningoencephalitis. The causative agents associated with meningoencephalitis of broilers that had not been identified by routine diagnostic methods could be diagnosed by metagenomics, which proves the usefulness of metagenomics as a diagnostic tool for unknown neurological diseases in broilers.
Topics: Animals; Chickens; Newcastle disease virus; Newcastle Disease; Brain; Meningoencephalitis; Poultry Diseases
PubMed: 37798783
DOI: 10.1186/s12917-023-03732-y -
Biomedical Journal Mar 2024Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and... (Review)
Review
Enterovirus A71 (EV-A71) infections pose a significant public health concern in the Asia-Pacific region. EV-A71 is primarily responsible for causing hand, foot, and mouth disease (HFMD) in children. However, this virus can also lead to severe and potentially fatal neurological consequences in affected individuals. This review aims to provide a comprehensive understanding of the molecular virology, epidemiology, and recombination events associated with EV-A71. The literature extensively covers the clinical manifestations and neurological symptoms that accompany EV-A71 infections. One of the complications explored in this review is brainstem encephalitis, which can arise as a result of EV-A71 infections. Brainstem encephalitis refers to inflammation of the brainstem, a critical region responsible for various bodily functions. The review examines the underlying mechanisms, diagnostic criteria, treatment options, and prognosis for central nervous system infections involving EV-A71. Neurological complications associated with EV-A71 infections are diverse and can have severe consequences. These complications may include aseptic meningitis, acute flaccid paralysis, and acute transverse myelitis. The review delves into the pathophysiology of these complications, shedding light on the molecular mechanisms through which EV-A71 affects the central nervous system. Accurate diagnosis of EV-A71 infections is crucial for appropriate management and treatment. Treatment options for EV-A71 infections primarily focus on supportive care, as there are currently no specific antiviral drugs available for this virus. The review highlights the importance of managing symptoms, such as fever, dehydration, and pain relief, to alleviate the burden on affected individuals. Prognosis for individuals with central nervous system (CNS) infections involving EV-A71 can vary depending on the severity of the complications. The review provides insights into the long-term outcomes and potential neurological sequelae associated with EV-A71 infections. In conclusion, EV-A71 infections have emerged as a major public health concern in the Asia-Pacific region. This review aims to enhance our understanding of the molecular virology, epidemiology, and neurological complications associated with EV-A71. By examining the underlying mechanisms, diagnostic criteria, treatment options, and prognosis, this review contributes to the development of effective strategies for the prevention, diagnosis, and management of EV-A71 infections. The paper presents a comprehensive analysis of worldwide data pertaining to outbreaks of EV-A71 and HFMD. The subsequent discourse delves into the advancement and strategic formulation pertaining to the creation of vaccines targeting EV-A71. In summary, this study provides a comprehensive examination of the potential obstacles and considerations involved in the management and treatment of EV-A71 infections. Additionally, it proposes suggestions for future research and development endeavors with the objective of formulating efficacious treatment approaches for this viral infection.
PubMed: 38492637
DOI: 10.1016/j.bj.2024.100715 -
PloS One 2023Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB,...
Enterovirus B (EVB) is a common species of enterovirus, mainly consisting of Echovirus (Echo) and Coxsackievirus B (CVB). The population is generally susceptible to EVB, especially among children. Since the 21st century, EVB has been widely prevalent worldwide, and can cause serious diseases, such as viral meningitis, myocarditis, and neonatal sepsis. By using cryo-electron microscopy, the three-dimensional (3D) structures of EVB and their uncoating receptors (FcRn and CAR) have been determined, laying the foundation for the study of viral pathogenesis and therapeutic antibodies. A limited number of epitopes bound to neutralizing antibodies have also been determined. It is unclear whether additional epitopes are present or whether epitope mutations play a key role in molecular evolutionary history and epidemics, as in influenza and SARS-CoV-2. In the current study, the conformational epitopes of six representative EVB serotypes (E6, E11, E30, CVB1, CVB3 and CVB5) were systematically predicted by bioinformatics-based epitope prediction algorithm. We found that their epitopes were distributed into three clusters, where the VP1 BC loop, C-terminus and VP2 EF loop were the main regions of EVB epitopes. Among them, the VP1 BC loop and VP2 EF loop may be the key epitope regions that determined the use of the uncoating receptors. Further molecular evolution analysis based on the VP1 and genome sequences showed that the VP1 C-terminus and VP2 EF loop, as well as a potential "breathing epitope" VP1 N-terminus, were common mutation hotspot regions, suggesting that the emergence of evolutionary clades was driven by epitope mutations. Finally, footprints showed mutations were located on or near epitopes, while mutations on the receptor binding sites were rare. This suggested that EVB promotes viral epidemics by breaking the immune barrier through epitope mutations, but the mutations avoided the receptor binding sites. The bioinformatics study of EVB epitopes may provide important information for the monitoring and early warning of EVB epidemics and developing therapeutic antibodies.
Topics: Humans; Capsid; Cryoelectron Microscopy; COVID-19; SARS-CoV-2; Capsid Proteins; Enterovirus B, Human; Epitopes; Mutation
PubMed: 37639390
DOI: 10.1371/journal.pone.0290584 -
The American Journal of Case Reports Dec 2023BACKGROUND The highly active antiretroviral treatment (HAART) and the primary prophylaxis in newly diagnosed people living with HIV (PLHIV) have reduced the incidence of... (Review)
Review
BACKGROUND The highly active antiretroviral treatment (HAART) and the primary prophylaxis in newly diagnosed people living with HIV (PLHIV) have reduced the incidence of opportunistic infections such as cryptococcal meningitis (CM). Relapse of CM is associated with increased morbidity and mortality. The aim of the present case presentation is to report the clinical progress relapse of CM in a man who was a late presenter PLHIV, 1 year after ART initiation with increased CD4 cell count, undetectable viral load, and excellent compliance after disruption of secondary antifungal prophylaxis. CASE REPORT One year after initial diagnosis of HIV and CM, the patient had no neurological or other symptoms, and viral suppression and increased CD4 cell count were achieved. After the completion of 12 months of secondary prophylaxis with fluconazole, an episode of partial seizure with secondary generalization occurred, followed by a short-term memory loss. Magnetic resonance imaging (MRI) indicated a focal lesion in right frontal-parietal brain region. Lumbar puncture was conducted and Cryptococcus neoformans non-resistant to fluconazole was isolated. He received antiepileptic treatment, induction antifungal treatment with liposomal amphotericin and fluconazole, consolidation treatment with fluconazole, and secondary prophylaxis with fluconazole, as in the first episode of CM. One year after the relapse, antiepileptic treatment and secondary prophylaxis with fluconazole continues and no new episode has been reported. The diagnosis of immune reconstitution inflammatory syndrome (IRIS)-related relapse of CM cannot be excluded. CONCLUSIONS Further studies are needed for the evaluation of parameters such as duration of secondary prophylaxis and treatment options for induction and consolidation therapy to reduce the relapse rate of CM.
Topics: Male; Humans; Meningitis, Cryptococcal; Antifungal Agents; Fluconazole; AIDS-Related Opportunistic Infections; Anticonvulsants; Neoplasm Recurrence, Local; Recurrence; HIV Infections
PubMed: 38083828
DOI: 10.12659/AJCR.941714 -
Current Research in Microbial Sciences 2023Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and...
Infection with coxsackievirus A10 (CV-A10) can cause hand-foot-mouth disease and is also associated with severe complications, including viral pneumonia, aseptic and viral meningitis. Coxsackievirus infection may also play a role in the pathogenesis of acute myocardial infarction and in the increased risk of type 1 diabetes mellitus in adults. However, there are no approved vaccines or direct antiviral agents available to prevention or treatment of coxsackievirus infection. Here, we reported that GC376 potently inhibited CV-A10 infection in different cell lines without cytotoxicity, significantly suppressed production of viral proteins, and strongly reduced the yields of infectious progeny virions. Further study indicated that GC376, as viral 3C protease inhibitor, had the potential to restrain the cleavage of the viral polyprotein into individually functional proteins, thus suppressed the replication of CV-A10. Furthermore, the drug exhibited antiviral activity against coxsackieviruses of various serotypes including CV-A6, CV-A7 and CV-A16, suggesting that GC376 is a broad-spectrum anti-coxsackievirus inhibitor and the 3C protease is a promising target for developing anti-coxsackievirus agents.
PubMed: 37767059
DOI: 10.1016/j.crmicr.2023.100203 -
The Journal of Antimicrobial... Aug 2023Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent...
BACKGROUND
Infection with ESBL-producing Enterobacteriaceae infection is ubiquitous in some neonatal ICUs and increasing levels of antibiotic resistance are a cause for urgent concern. Delineation of bacterial and viral sepsis can be challenging, often leading to patients receiving empirical antibiotics without or whilst waiting for a definitive causal diagnosis. Empirical therapy is often dependent on broad-spectrum 'Watch' antibiotics, contributing to further resistance.
METHODS
ESBL-producing Enterobacteriaceae clinical isolates found to have caused neonatal sepsis and meningitis underwent a detailed in vitro screening including susceptibility testing, chequerboard combination analysis and hollow-fibre infection model dynamic analyses using combinations of cefotaxime, ampicillin and gentamicin in combination with β-lactamase inhibitors.
RESULTS
Additivity or synergy was found for all antibiotic combinations against seven Escherichia coli and three Klebsiella pneumoniae clinical isolates. Cefotaxime or ampicillin plus sulbactam combined with gentamicin was able to consistently inhibit the growth of ESBL-producing isolates at typical neonatal doses, and the combination cleared the hollow-fibre infection model system of organisms resistant to each agent alone. The combination of cefotaxime/sulbactam and gentamicin was consistently bactericidal at clinically achievable concentrations (Cmax of 180, 60 and 20 mg/L for cefotaxime, sulbactam and gentamicin, respectively).
CONCLUSIONS
The addition of sulbactam to cefotaxime or ampicillin to the typical first-line empirical therapy could obviate the need for carbapenems and amikacin in settings with high ESBL-infection prevalence.
Topics: Infant, Newborn; Humans; Amikacin; Carbapenems; Sulbactam; Gentamicins; Neonatal Sepsis; Prevalence; Anti-Bacterial Agents; Cefotaxime; Ampicillin; Escherichia coli; beta-Lactamases; Microbial Sensitivity Tests
PubMed: 37283195
DOI: 10.1093/jac/dkad177 -
The Lancet. Infectious Diseases Apr 2024The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and...
BACKGROUND
The COVID-19 pandemic is reported to have affected the epidemiology of respiratory syncytial virus (RSV), which could have important implications for RSV prevention and control strategies. We aimed to assess the hospitalisation burden of RSV-associated acute lower respiratory infection (ALRI) in children younger than 5 years during the pandemic period and the possible changes in RSV epidemiology from a global perspective.
METHODS
We conducted a systematic literature search for studies published between Jan 1, 2020, and June 30, 2022, in MEDLINE, Embase, Global Health, Web of Science, the WHO COVID-19 Research Database, CINAHL, LILACS, OpenGrey, CNKI, WanFang, and CqVip. We included unpublished data on RSV epidemiology shared by international collaborators. Eligible studies reported data on at least one of the following measures for children (aged <5 years) hospitalised with RSV-associated ALRI: hospital admission rates, in-hospital case fatality ratio, and the proportion of hospitalised children requiring supplemental oxygen or requiring mechanical ventilation or admission to intensive care. We used a generalised linear mixed-effects model for data synthesis to measure the changes in the incidence, age distribution, and disease severity of children hospitalised with RSV-associated ALRI during the pandemic, compared with the year 2019.
FINDINGS
We included 61 studies from 19 countries, of which 14 (23%) studies were from the published literature (4052 identified records) and 47 (77%) were from unpublished datasets. Most (51 [84%]) studies were from high-income countries; nine (15%) were from upper-middle-income countries, one (2%) was from a lower-middle-income country (Kenya), and none were from a low-income country. 15 studies contributed to the estimates of hospitalisation rate and 57 studies contributed to the severity analyses. Compared with 2019, the rates of RSV-associated ALRI hospitalisation in all children (aged 0-60 months) in 2020 decreased by 79·7% (325 000 cases vs 66 000 cases) in high-income countries, 13·8% (581 000 cases vs 501 000 cases) in upper-middle-income countries, and 42·3% (1 378 000 cases vs 795 000 cases) in Kenya. In high-income countries, annualised rates started to rise in 2021, and by March, 2022, had returned to a level similar to 2019 (6·0 cases per 1000 children [95% uncertainty interval 5·4-6·8] in April, 2021, to March, 2022, vs 5·0 cases per 1000 children [3·6-6·8] in 2019). By contrast, in middle-income countries, rates remained lower in the latest period with data available than in 2019 (for upper-middle-income countries, 2·1 cases [0·7-6·1] in April, 2021, to March, 2022, vs 3·4 [1·2-9·7] in 2019; for Kenya, 2·2 cases [1·8-2·7] in 2021 vs 4·1 [3·5-4·7] in 2019). Across all time periods and income regions, hospitalisation rates peaked in younger infants (aged 0 to <3 months) and decreased with increasing age. A significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high-income and upper-middle-income countries during the pandemic years than in 2019, with odds ratios ranging from 1·30 (95% uncertainty interval 1·07-1·59) to 2·05 (1·66-2·54). No consistent changes in disease severity were observed.
INTERPRETATION
The hospitalisation burden of RSV-associated ALRI in children younger than 5 years was significantly reduced during the first year of the COVID-19 pandemic. The rebound in hospitalisation rates to pre-pandemic rates observed in the high-income region but not in the middle-income region by March, 2022, suggests a persistent negative impact of the pandemic on health-care systems and health-care access in the middle-income region. RSV surveillance needs to be established (or re-established) to monitor changes in RSV epidemiology, particularly in low-income and lower-middle-income countries.
FUNDING
EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE), Bill & Melinda Gates Foundation, and WHO.
Topics: Infant; Child; Humans; Child, Preschool; Pandemics; COVID-19; Hospitalization; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Respiratory Syncytial Virus Infections
PubMed: 38141633
DOI: 10.1016/S1473-3099(23)00630-8 -
The Pediatric Infectious Disease Journal Apr 2024Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous... (Observational Study)
Observational Study
BACKGROUND
Multiplex polymerase chain reaction assays have the potential to reduce antibiotic use and shorten length of inpatient stay in children with suspected central nervous system infection by obtaining an early microbiological diagnosis. The clinical impact of the implementation of the BioFire FilmArray Meningitis/Encephalitis Panel on the management of childhood meningitis was evaluated at the John Radcliffe Hospital in Oxford and Children's Health Ireland at Temple Street in Dublin.
METHODS
Children who had lumbar punctures performed as part of a septic screen were identified retrospectively through clinical discharge coding and microbiology databases from April 2017 to December 2018. Anonymized clinical and laboratory data were collected. Comparison of antibiotic use, length of stay and outcome at discharge was made with a historical cohort in Oxford (2012-2016), presenting before implementation of the FilmArray.
RESULTS
The study included 460 children who had a lumbar puncture as part of an evaluation for suspected central nervous system infection. Twelve bacterial cases were identified on the FilmArray that were not detected by conventional bacterial culture. Bacterial culture identified one additional case of bacterial meningitis, caused by Escherichia coli , which had not been identified on the FilmArray. Duration of antibiotics was shorter in children when FilmArray was used than before its implementation; enterovirus meningitis (median: 4 vs. 5 days), human parechovirus meningitis (median: 4 vs. 4.5 days) and culture/FilmArray-negative cerebrospinal fluid (median: 4 vs. 6 days).
CONCLUSIONS
The use of a FilmArray can identify additional bacterial cases of meningitis in children that had been negative by traditional culture methods. Children with viral meningitis and culture-negative meningitis received shorter courses of antibiotics and had shorter hospital stays when FilmArray was used. Large studies to evaluate the clinical impact and cost effectiveness of incorporating the FilmArray into routine testing are warranted.
Topics: Child; Humans; Encephalitis; Retrospective Studies; Meningitis; Cohort Studies; Meningitis, Bacterial; Bacteria; Multiplex Polymerase Chain Reaction; Central Nervous System Infections; Anti-Bacterial Agents; Meningitis, Viral
PubMed: 38190645
DOI: 10.1097/INF.0000000000004236