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PloS One 2024Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by...
Tick-borne encephalitis (TBE) is usually diagnosed based on the presence of TBE virus (TBEV)-specific IgM and IgG antibodies in serum. However, antibodies induced by vaccination or cross-reactivity to previous flavivirus infections may result in false positive TBEV serology. Detection of TBEV RNA may be an alternative diagnostic approach to detect viral presence and circumvent the diagnostic difficulties present when using serology. Viral RNA in blood is commonly detectable only in the first viremic phase usually lasting up to two weeks, and not in the second neurologic phase, when the patients contact the health care system and undergo diagnostic work-up. TBEV RNA has previously been detected in urine in a few retrospective TBE cases in the neurologic phase, and furthermore RNA of other flaviviruses has been detected in patient saliva. In this study, blood, saliva and urine were collected from 31 hospitalised immunocompetent patients with pleocytosis and symptoms of aseptic meningitis and/or encephalitis, suspected to have TBE. We wanted to pursue if molecular testing of TBEV RNA in these patient materials may be useful in the diagnostics. Eleven of the 31 study patients were diagnosed with TBE based on ELISA detection of TBEV specific IgG and IgM antibodies. None of the study patients had TBEV RNA detectable in any of the collected patient material.
Topics: Humans; Encephalitis, Tick-Borne; Encephalitis Viruses, Tick-Borne; Saliva; RNA, Viral; Male; Female; Middle Aged; Adult; Aged; Immunoglobulin M; Immunoglobulin G; Antibodies, Viral; Aged, 80 and over; Immunocompetence; Hospitalization
PubMed: 38913668
DOI: 10.1371/journal.pone.0305603 -
Ugeskrift For Laeger Jun 2024Ramsay Hunt syndrome (RHS) is an infection with the Varicella Zoster virus in the geniculate ganglion of the facial nerve. The syndrome consists of a triad of peripheral...
Ramsay Hunt syndrome (RHS) is an infection with the Varicella Zoster virus in the geniculate ganglion of the facial nerve. The syndrome consists of a triad of peripheral facial nerve palsy, ear pain and concurrent zoster rash in the ear canal. However, vesicles in the mouth can be seen. A rare complication of RHS is viral meningitis. This is a case report of a patient with orally manifested RHS and concurrent asymptomatic viral meningitis. This case aims to raise awareness of RHS with atypical presentation and concurrent viral meningitis and, thereby, the importance of a thorough neurological examination.
Topics: Humans; Herpes Zoster Oticus; Meningitis, Viral; Male; Female; Middle Aged
PubMed: 38903036
DOI: 10.61409/V02240092 -
Journal of Translational Medicine Jun 2024Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity,...
BACKGROUND
Infectious meningitis/encephalitis (IM) is a severe neurological disease that can be caused by bacterial, viral, and fungal pathogens. IM suffers high morbidity, mortality, and sequelae in childhood. Metagenomic next-generation sequencing (mNGS) can potentially improve IM outcomes by sequencing both pathogen and host responses and increasing the diagnosis accuracy.
METHODS
Here we developed an optimized mNGS pipeline named comprehensive mNGS (c-mNGS) to monitor DNA/RNA pathogens and host responses simultaneously and applied it to 142 cerebrospinal fluid samples. According to retrospective diagnosis, these samples were classified into three categories: confirmed infectious meningitis/encephalitis (CIM), suspected infectious meningitis/encephalitis (SIM), and noninfectious controls (CTRL).
RESULTS
Our pipeline outperformed conventional methods and identified RNA viruses such as Echovirus E30 and etiologic pathogens such as HHV-7, which would not be clinically identified via conventional methods. Based on the results of the c-mNGS pipeline, we successfully detected antibiotic resistance genes related to common antibiotics for treating Escherichia coli, Acinetobacter baumannii, and Group B Streptococcus. Further, we identified differentially expressed genes in hosts of bacterial meningitis (BM) and viral meningitis/encephalitis (VM). We used these genes to build a machine-learning model to pinpoint sample contaminations. Similarly, we also built a model to predict poor prognosis in BM.
CONCLUSIONS
This study developed an mNGS-based pipeline for IM which measures both DNA/RNA pathogens and host gene expression in a single assay. The pipeline allows detecting more viruses, predicting antibiotic resistance, pinpointing contaminations, and evaluating prognosis. Given the comparable cost to conventional mNGS, our pipeline can become a routine test for IM.
Topics: Humans; Prognosis; Child; Encephalitis; Child, Preschool; Meningitis, Bacterial; Male; Female; Metagenomics; Infant; High-Throughput Nucleotide Sequencing; RNA
PubMed: 38902725
DOI: 10.1186/s12967-024-05370-w -
Revista Brasileira de Epidemiologia =... 2024To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019.
OBJECTIVE
To analyze the spatiotemporal epidemiological dynamics of meningitis in Brazil, between 2010 and 2019.
METHODS
Descriptive ecological study with cases and deaths due to meningitis in Brazil (2010-2019) in the National Notifiable Diseases Information System (Sistema de Informações de Agravos de Notificação - SINAN). The following analyses were performed: (I) frequency analyses of cases and deaths, prevalence rates, mortality, lethality, Fisher's exact test, and chi-square test; (II) Prais-Winstein regression; and (III) Global, Local Moran's index, and Kernel density.
RESULTS
182,126 cases of meningitis were reported in Brazil, of which 16,866 (9.26%) resulted in death, with prevalence rates of 9.03/100,000 inhabitants, mortality of 0.84/100,000 inhabitants, and lethality of 9.26%. There was a noted trend of decreasing prevalence rates (-9.5%, 95% confidence interval - 95%CI -13.92; -4.96, p<0.01) and mortality (-11.74%, 95%CI -13.92; -9.48, p<0.01), while lethality remained stable (-2.08%, 95%CI -4.9; 0.8; p<0.1941). The majority of cases were viral meningitis (45.7%), among 1-9 years old (32.2%), while the highest proportion of deaths was due to bacterial meningitis (68%), among 40-59 years old (26.3%). In the Moran and Kernel maps of prevalence and mortality rates, municipalities in the South, Southeast, and the capital of Pernambuco in the Northeast stood out with high rates; as for lethality, the North, Northeast, and Southeast coastal areas were highlighted.
CONCLUSION
A decrease in meningitis cases and deaths was found in this study; however, the lethality rate was higher in areas with lower prevalence, emphasizing the need to enhance actions for identifying, monitoring, and providing health care for cases, as well as expanding vaccination coverage.
Topics: Brazil; Humans; Prevalence; Adult; Child; Infant; Meningitis; Adolescent; Middle Aged; Child, Preschool; Young Adult; Male; Female; Spatio-Temporal Analysis; Public Health; Age Distribution; Time Factors; Infant, Newborn; Meningitis, Bacterial
PubMed: 38896651
DOI: 10.1590/1980-549720240031 -
Eastern Mediterranean Health Journal =... May 2024Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200...
BACKGROUND
Meningitis is still a major public health challenge globally. Both the viral and bacterial forms of the disease have been reported worldwide. In 2023, around 200 children with suspected meningitis were admitted to hospital in Halabja Governorate, Iraq. No outbreak of meningitis had been reported previously in that region.
AIMS
To investigate the aetiology and epidemiology of meningitis among children in Halabja Governorate, Iraq, and expedite clinical management and prevention.
METHODOLOGY
Blood and cerebrospinal fluid specimens were collected from 197 children admitted to Halabja Paediatric and Maternity Teaching Hospital from 1 March to 1 July 2023 and analysed. The sample t-test was used to compare the haematological, serological and biochemical characteristics of the samples.
RESULTS
The majority (76.6%) of the children were aged 2-9 years and 54% were males. The clinical manifestations of the disease were fever (100.0%), headache (89.0%), vomiting (85.7%), and photophobia (72.4%); none of the children had convulsions. The mean values for both neutrophil count and C-reactive protein were statistically significantly raised (P < 0.05) and the red blood cells, white blood cells and neutrophil counts, and lactate dehydrogenase values were statistically significantly raised (P < 0.05). The causative organism was enterovirus (98.5%), with sporadic cases of streptococcal meningitis (1.5%). All the patients recovered fully.
CONCLUSION
The rapid diagnosis of the disease was crucial to the therapeutic and prevention control measures for the outbreak. Although it is still unclear how and where this outbreak started, contaminated drinking water and transmission among children in nurseries and schools are suspected. Further investigations are recommended to determine the source of the enterovirus and identify the virus species and serotypes.
Topics: Humans; Iraq; Child; Child, Preschool; Male; Disease Outbreaks; Female; Meningitis, Viral; Adolescent; Infant; Meningitis, Bacterial
PubMed: 38874294
DOI: 10.26719/2024.30.5.350 -
PLoS Neglected Tropical Diseases Jun 2024Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in...
BACKGROUND
Tacheng tick virus 2 (TcTV-2) is an emerging tick-borne virus belonging to the genus Uukuvirus in the family Phenuiviridae. Initially isolated in 2019 from a patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China, who developed fever and headache after a tick bite, TcTV-2 was concurrently molecularly detected in hard ticks across various countries, including China, Kazakhstan, Romania, and Turkey. This study conducted a retrospective epidemiological investigation of TcTV-2 infection.
METHODOLOGY
In this retrospective cohort study, we collected samples from 47 tick-bitten patients, 984 herdsmen, 7 Asian badgers, 13 red foxes, and 168 Hyalomma asiaticum tick egg batches. Patients' samples were primarily analyzed by using high-throughput sequencing, targeting the V3-V4 region of the bacterial 16S rRNA gene and viral cDNA libraries. Typical tick-borne pathogens were further confirmed using RT-PCR and detected in Asian badgers, red foxes and Hy. asiaticum tick egg batches. We also conducted enzyme-linked immunosorbent assay (ELISA) to detected specific IgM and IgG antibodies against TcTV-2 in herdsmen. Phylogenetic analysis was performed to genetically characterize TcTV-2 detected in this study.
PRINCIPAL FINDINGS
TcTV-2 was detected in various samples, including blood, urine, and throat swabs from 12.77% (6/47) tick-bitten patients. It was found in blood samples of 14.29% (1/7) of wild badgers, 7.69% (1/13) of red foxes, and 13.69% (23/168) of Hy. asiaticum egg batches. Furthermore, ELISA results revealed that 9.55% (94/984) of the serum samples (34 from males and 60 from females) were tested positive for TcTV-2-specific IgG, while 2.95% (29/984, 7 males and 22 females) showed positivity for TcTV-2-specific IgM. Additionally, 1.02% (10/984, 4 males and 6 females) of the sera tested positive for both TcTV-2-specific IgM and IgG. Phylogenetic analysis indicated that the TcTV-2 strains detected in this study were genetically similar, regardless of their origin and host species.
CONCLUSIONS
Clinical symptoms of TcTV-2 infection in patients are nonspecific, with common symptoms including headache, fever, asthenia, vomiting, myalgia, rash, and meningitis-like signs. TcTV-2 can be detected in blood, urine, and throat swab samples of infected patients. Among local herdsmen, 9.55% tested positive for TcTV-2-specific IgG and 2.95% for TcTV-2-specific IgM. Importantly, TcTV-2 can be transovarially transmitted in Hy. asiaticum ticks, and the Asian badgers and red foxes are potential reservoirs of TcTV-2.
Topics: Retrospective Studies; Animals; Male; Humans; Female; Phylogeny; Middle Aged; Adult; China; Antibodies, Viral; Young Adult; Immunoglobulin G; Adolescent; Immunoglobulin M; Tick-Borne Diseases; Aged; Child; Tick Bites; Foxes
PubMed: 38870100
DOI: 10.1371/journal.pntd.0012168 -
Virus Research Aug 2024The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other...
The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993-2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.
Topics: JC Virus; Phylogeography; Humans; Phylogeny; Genome, Viral; Leukoencephalopathy, Progressive Multifocal; Polyomavirus Infections; Genetic Variation; Cluster Analysis
PubMed: 38848817
DOI: 10.1016/j.virusres.2024.199414 -
Infection, Genetics and Evolution :... Aug 2024Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most...
Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most cases, was shown to cause disease in humans, mainly fever and meningitis. By means of genetic analysis of part of M segment, we describe 3 new viral isolates obtained directly from cerebrospinal fluid or sera samples of patients diagnosed with TosV infection in July 2020 in Tuscany region. Phylogenesis was used to propose the clustering of TosV lineage A strains in 3 main groups, whereas deep mutational analysis based on 12 amino acid positions, allowed the identification of 9 putative strains. We discuss deep mutational analysis as a method to identify molecular signature of host adaptation and/or pathogenesis.
Topics: Humans; Italy; Phylogeny; Sandfly fever Naples virus; Genome, Viral; Evolution, Molecular; Genomics; Male
PubMed: 38830443
DOI: 10.1016/j.meegid.2024.105601 -
Frontiers in Immunology 2024Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments...
INTRODUCTION
Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments differ. Utilizing single-cell RNA sequencing (scRNA-seq) data from mice, we tested the hypothesis that retinal and brain microglia exhibit distinct transcriptional profiles due to their unique microenvironments.
METHODS
Eyes and brains from 2-4 month wildtype mice were combined (20 eyes; 3 brains) to yield one biologically diverse sample per organ. Each tissue was digested into single cell suspensions, enriched for immune cells, and sorted for scRNA-seq. Analysis was performed in Seurat v3 including clustering, integration, and differential expression. Multi-parameter flow cytometry was used for validation of scRNA-seq results. Lymphocytic choriomeningitis virus (LCMV) Clone 13, which produces a systemic, chronic, and neurotropic infection, was used to validate scRNA-seq and flow cytometry results .
RESULTS
Cluster analysis of integrated gene expression data from eye and brain identified 6 microglial clusters. Differential expression analysis revealed that eye microglia were enriched for more pro-inflammatory processes including antigen processing via MHC class I (14.0-fold, and ) and positive regulation of T-cell immunity (8.4-fold) compared to brain microglia. Multi-parameter flow cytometry confirmed that retinal microglia expressed 3.2-fold greater H2-Db and 263.3-fold more H2-Kb than brain microglia. On Day 13 and 29 after LCMV infection, CD8 T-cell density was greater in the retina than the brain.
DISCUSSION
Our data demonstrate that the microenvironment of retina and brain differs, resulting in microglia-specific gene expression changes. Specifically, retinal microglia express greater MHC class I by scRNA-seq and multi-parameter flow cytometry, resulting in a possibly enhanced capability to stimulate CD8 T-cell inflammation during LCMV infection. These results may explain tissue-specific differences between retina and brain during systemic viral infections and CD8 T-cell driven autoimmune disease.
Topics: Animals; Microglia; Mice; Retina; Brain; Mice, Inbred C57BL; Lymphocytic choriomeningitis virus; Histocompatibility Antigens Class I; T-Lymphocytes; Inflammation; Lymphocytic Choriomeningitis; Single-Cell Analysis; CD8-Positive T-Lymphocytes; Transcriptome
PubMed: 38799448
DOI: 10.3389/fimmu.2024.1399989