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Pathogens (Basel, Switzerland) Mar 2022The tick-borne encephalitis virus (TBEV) causes a life-threatening disease named Tick-borne encephalitis (TBE). The clinical symptoms associated with TBE range from...
The tick-borne encephalitis virus (TBEV) causes a life-threatening disease named Tick-borne encephalitis (TBE). The clinical symptoms associated with TBE range from non-specific to severe inflammation of the central nervous system and are very similar to the clinical presentation of other viral meningitis/encephalitis. In consequence, TBE is often misclassified by clinical physicians, mainly in the non-identified high-risk areas where none or only a few TBE cases have been reported. Considering this situation, we hypothesized that among persons from northern Serbia who recovered from viral meningitis or encephalitis, there would be evidence of TBEV infection. To test this hypothesis, in this observational study, we evaluated the seroreactivity against TBEV antigens in patients from northern Serbia who were hospitalized due to viral meningitis and/or viral encephalitis of unknown etiology. Three cases of seroreactivity to TBEV antigens were discovered among convalescent patients who recovered from viral meningitis and/or encephalitis and accepted to participate in the study ( = 15). The clinical and laboratory findings of these patients overlap with that of seronegative convalescent patients. Although TBE has been a notifiable disease in Serbia since 2004, there is no active TBE surveillance program for the serologic or molecular screening of TBEV infection in humans in the country. This study highlights the necessity to increase the awareness of TBE among physicians and perform active and systematic screening of TBEV antibodies among patients with viral meningitis and/or encephalitis.
PubMed: 35335695
DOI: 10.3390/pathogens11030371 -
Infection and Drug Resistance 2021Viral meningitis is common in most resource-limited settings, posing a challenge for the management and prognosis of suspected patients. No study has been done on the...
INTRODUCTION
Viral meningitis is common in most resource-limited settings, posing a challenge for the management and prognosis of suspected patients. No study has been done on the detection of either viral or viral-bacterial co-infection among presumed pyogenic meningitis cases in Ethiopia. We, therefore, aimed to determine the distribution of cytomegalovirus (CMV) and human enteroviruses (HEVs) among patients with presumptive pyogenic meningitis at University hospitals in Ethiopia.
METHODS
Viral nucleic acid was extracted from 86 repository CSF samples, which were collected from patients presumptively diagnosed with pyogenic meningitis between 2012 and 2013. PCR was done consecutively to investigate the possible viral etiologic agents of meningitis.
RESULTS
HEVs were detected in 11 (12.8%) of the analyzed samples while none of the 86 samples were tested positive for CMV. Viral-bacterial co-infections were found among 4/11 (36.4%) confirmed cases. The majority of the patients (10/11) with HEVs were younger aged ≤ 19 years old.
CONCLUSIONS
In this study, the magnitude of HEVs was shown to have a significant role in presumed pyogenic meningitis cases. Therefore, we recommend presumed pyogenic meningitis cases to be inspected for viral etiologies and improve meningeal symptoms interpretations.
PubMed: 33762832
DOI: 10.2147/IDR.S304521 -
Annals of Neurology Jul 2020In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over... (Review)
Review
In less than 6 months, the severe acute respiratory syndrome-coronavirus type 2 (SARS-CoV-2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID-19) also involves multiple other organs, including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS-CoV-2 infection is rapidly accumulating. These may result from a variety of mechanisms, including virus-induced hyperinflammatory and hypercoagulable states, direct virus infection of the central nervous system (CNS), and postinfectious immune mediated processes. Example of COVID-19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis, and endothelialitis. In the peripheral nervous system, COVID-19 is associated with dysfunction of smell and taste, muscle injury, the Guillain-Barre syndrome, and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID-19 poses a global threat to the entire nervous system. Although our understanding of SARS-CoV-2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID-19. ANN NEUROL 2020;88:1-11 ANN NEUROL 2020;88:1-11.
Topics: Betacoronavirus; Brain Diseases; Brain Ischemia; COVID-19; Coronavirus Infections; Disseminated Intravascular Coagulation; Encephalitis; Encephalomyelitis, Acute Disseminated; Guillain-Barre Syndrome; Humans; Inflammation; Intracranial Hemorrhages; Leukoencephalitis, Acute Hemorrhagic; Meningitis, Viral; Nervous System Diseases; Olfaction Disorders; Pandemics; Pneumonia, Viral; SARS-CoV-2; Sinus Thrombosis, Intracranial; Stroke; Thrombophilia
PubMed: 32506549
DOI: 10.1002/ana.25807 -
Cureus Apr 2021Drug-induced aseptic meningitis is a rare entity. Diagnosis of drug-induced aseptic meningitis can be challenging due to the difficulty in distinguishing clinical...
Drug-induced aseptic meningitis is a rare entity. Diagnosis of drug-induced aseptic meningitis can be challenging due to the difficulty in distinguishing clinical presentation from bacterial or viral meningitis. We present a case of a 52-year-old Caucasian female patient who presented to the emergency room on two different occasions with severe headache, neck pain, and confusion. Initial cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, and empirical intravenous acyclovir was initiated. Bacterial and viral CSF analysis and cultures were negative. The patient completely recovered. Several days later, the patient returned to the emergency room with similar symptoms. Second CSF analysis revealed neutrophilic pleocytosis, and empirical intravenous antibiotic and antiviral therapy were started. Bacterial, fungal, and viral CSF analysis and cultures were negative. Imaging studies of the brain were unremarkable on both occasions. The patient reported taking trimethoprim-sulfamethoxazole (TMP-SMX) for right foot infection before and after the initial presentation. The patient's symptoms resolved without neurological sequelae after discontinuation of TMP-SMX. This case report highlights the importance of taking a detailed history to diagnose drug-induced aseptic meningitis.
PubMed: 33996314
DOI: 10.7759/cureus.14454 -
Frontiers in Immunology 2024The host immune response determines the differential outcome of acute or chronic viral infections. The comprehensive comparison of lymphoid tissue immune cells at the...
INTRODUCTION
The host immune response determines the differential outcome of acute or chronic viral infections. The comprehensive comparison of lymphoid tissue immune cells at the single-cell level between acute and chronic viral infections is largely insufficient.
METHODS
To explore the landscape of immune responses to acute and chronic viral infections, single-cell RNA sequencing(scRNA-seq), scTCR-seq and scBCR-seq were utilized to evaluate the longitudinal dynamics and heterogeneity of lymph node CD45 immune cells in mouse models of acute (LCMV Armstrong) and chronic (LCMV clone 13) viral infections.
RESULTS
In contrast with acute viral infection, chronic viral infection distinctly induced more robust NK cells and plasma cells at the early stage (Day 4 post-infection) and acute stage (Day 8 post-infection), respectively. Moreover, chronic viral infection exerted decreased but aberrantly activated plasmacytoid dendritic cells (pDCs) at the acute phase. Simultaneously, there were significantly increased IgA plasma cells (MALT B cells) but differential usage of B-cell receptors in chronic infection. In terms of T-cell responses, Gzma-high effector-like CD8 T cells were significantly induced at the early stage in chronic infection, which showed temporally reversed gene expression throughout viral infection and the differential usage of the most dominant TCR clonotype. Chronic infection also induced more robust CD4 T cell responses, including follicular helper T cells (Tfh) and regulatory T cells (Treg). In addition, chronic infection compromised the TCR diversity in both CD8 and CD4 T cells.
DISCUSSION
In conclusion, gene expression and TCR/BCR immune repertoire profiling at the single-cell level in this study provide new insights into the dynamic and differential immune responses to acute and chronic viral infections.
Topics: Mice; Animals; CD8-Positive T-Lymphocytes; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Persistent Infection; Receptors, Antigen, T-Cell; Lymph Nodes; Sequence Analysis, RNA
PubMed: 38352870
DOI: 10.3389/fimmu.2024.1341985 -
Current Protocols in Immunology Sep 2020In this invited article, we explain technical aspects of the lymphocytic choriomeningitis virus (LCMV) system, providing an update of a prior contribution by Matthias...
In this invited article, we explain technical aspects of the lymphocytic choriomeningitis virus (LCMV) system, providing an update of a prior contribution by Matthias von Herrath and J. Lindsay Whitton. We provide an explanation of the LCMV infection models, highlighting the importance of selecting an appropriate route and viral strain. We also describe how to quantify virus-specific immune responses, followed by an explanation of useful transgenic systems. Specifically, our article will focus on the following protocols. © 2020 Wiley Periodicals LLC. Basic Protocol 1: LCMV infection routes in mice Support Protocol 1: Preparation of LCMV stocks ASSAYS TO MEASURE LCMV TITERS Support Protocol 2: Plaque assay Support Protocol 3: Immunofluorescence focus assay (IFA) to measure LCMV titer MEASUREMENT OF T CELL AND B CELL RESPONSES TO LCMV INFECTION Basic Protocol 2: Triple tetramer staining for detection of LCMV-specific CD8 T cells Basic Protocol 3: Intracellular cytokine staining (ICS) for detection of LCMV-specific T cells Basic Protocol 4: Enumeration of direct ex vivo LCMV-specific antibody-secreting cells (ASC) Basic Protocol 5: Limiting dilution assay (LDA) for detection of LCMV-specific memory B cells Basic Protocol 6: ELISA for quantification of LCMV-specific IgG antibody Support Protocol 4: Preparation of splenic lymphocytes Support Protocol 5: Making BHK21-LCMV lysate Basic Protocol 7: Challenge models TRANSGENIC MODELS Basic Protocol 8: Transfer of P14 cells to interrogate the role of IFN-I on CD8 T cell responses Basic Protocol 9: Comparing the expansion of naïve versus memory CD4 T cells following chronic viral challenge.
Topics: Adaptive Immunity; Animals; Antibodies, Viral; Antibody Specificity; B-Lymphocytes; Cell Culture Techniques; Cell Line; Cytokines; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Host-Pathogen Interactions; Immunologic Memory; Lymphocyte Depletion; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; T-Cell Antigen Receptor Specificity; T-Lymphocytes; Viral Load; Viral Plaque Assay
PubMed: 32940427
DOI: 10.1002/cpim.99 -
European Journal of Neurology Jan 2024Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited.
BACKGROUND AND PURPOSE
Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited.
METHODS
This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison.
RESULTS
Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis.
CONCLUSIONS
Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.
Topics: Adult; Humans; Cohort Studies; Meningitis, Viral; Aftercare; Polymerase Chain Reaction; Recurrence; Patient Discharge; Meningitis, Aseptic; Herpesvirus 2, Human; Denmark
PubMed: 37797296
DOI: 10.1111/ene.16081 -
BMJ Case Reports Aug 2020Bacterial co-infection in the ongoing pandemic of COVID-19 is associated with poor outcomes but remains little understood. A 22-year-old woman presented with a 3-week...
Bacterial co-infection in the ongoing pandemic of COVID-19 is associated with poor outcomes but remains little understood. A 22-year-old woman presented with a 3-week history of fever, headache, neck stiffness, rigours and confusion. She was noted to have a purpuric rash over her hands and feet. Cerebrospinal fluid bacterial PCR was positive for A concurrent nasopharyngeal RT-PCR was positive for SARS-CoV-2, the causative virus of COVID-19. She was treated with antibiotics for bacterial meningitis and made a complete recovery. Bacterial infection from nasopharyngeal organisms has followed previous pandemic viral upper respiratory illnesses and the risk of bacterial co-infection in COVID-19 remains unclear. Research characterising COVID-19 should specify the frequency, species and outcome of bacterial co-infection. Management of bacterial co-infection in COVID-19 presents major challenges for antimicrobial stewardship and clinical management. Judicious use of local antibiotic guidelines and early liaison with infection specialists is key.
Topics: Anti-Bacterial Agents; Betacoronavirus; COVID-19; Ceftriaxone; Coinfection; Coronavirus Infections; Female; Humans; Meningitis, Meningococcal; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2; Young Adult
PubMed: 32843469
DOI: 10.1136/bcr-2020-237366 -
Advanced Emergency Nursing Journal 2020Meningitis is a significant viral, bacterial, or fungal infection of the meninges that cover and protect the brain and the spinal cord. Symptoms of meningitis may...
Meningitis is a significant viral, bacterial, or fungal infection of the meninges that cover and protect the brain and the spinal cord. Symptoms of meningitis may present rapidly or develop gradually over a period of days, manifesting with common prodromal flu-like symptoms of headache, photophobia, fever, nuchal rigidity, myalgias, and fatigue. Character and significance of symptoms vary by patient age. Symptoms of infection may improve spontaneously or worsen, becoming potentially lethal. Early recognition and treatment of meningitis are crucial to prevent morbidity and mortality. The case reviewed in this article focuses on viral meningitis in a pediatric patient that may be unrecognized or underreported because of indistinct symptoms. Epidemiology, pathophysiology, presentation, assessment techniques, diagnostics, clinical management, and health promotion relevant to viral meningitis are presented.
Topics: Acetaminophen; Adolescent; Analgesics, Non-Narcotic; Diagnosis, Differential; Emergency Service, Hospital; Enterovirus Infections; Humans; Male; Meningitis, Viral; Pain Measurement
PubMed: 33105178
DOI: 10.1097/TME.0000000000000318 -
Journal of Virology May 2022Echovirus 30 (E30), a member of species B enterovirus, is associated with outbreaks of aseptic meningitis and has become a global health emergency. However, the...
Echovirus 30 (E30), a member of species B enterovirus, is associated with outbreaks of aseptic meningitis and has become a global health emergency. However, the pathogenesis of E30 remains poorly understood due to the lack of appropriate animal models. In this study, we established a mouse infection model to explore the pathogenicity of E30. The 2-day-old mice infected with E30 strain WZ16 showed lethargy and paralysis, and some died. Obvious pathological changes were observed in the skeletal muscle, brain tissue, and other tissues, with the highest viral load in the skeletal muscles. Transcriptome analysis of brain and skeletal muscle tissues from infected mice showed that significant differentially expressed genes were enriched in complement response and neuropathy-related pathways. Using immunofluorescence assay, we found that the viral double-stranded RNA (dsRNA) was detected in the mouse brain region and could infect human glioma (U251) cells. These results indicated that E30 affects the nervous system, and they provide a theoretical basis for understanding its pathogenesis. Echovirus 30 (E30) infection causes a wide spectrum of diseases with mild symptoms, such as hand, foot, and mouth disease (HFMD), acute flaccid paralysis, and aseptic meningitis and other diseases, especially one of the most common pathogens causing aseptic meningitis outbreaks. We established a novel mouse model of E30 infection by inoculating neonatal mice with clinical isolates of E30 and observed the pathological changes induced by E30. Using the E30 infection model, we found complement responses and neuropathy-related genes in the mice tissues at the transcriptome level. Moreover, we found that the viral dsRNA localized in the mouse brain and could replicate in human glioma cell line U251 rather than in the neuroblastoma cell line, SK-N-SH.
Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Echovirus Infections; Enterovirus B, Human; Glioma; Humans; Meningitis, Aseptic; Mice; Mice, Knockout; Phylogeny; RNA, Viral; Sequence Analysis, DNA
PubMed: 35420443
DOI: 10.1128/jvi.00129-22