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Current Opinion in Infectious Diseases Jun 2023The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and... (Review)
Review
PURPOSE OF REVIEW
The most common infectious etiologies of meningitis and encephalitis are viruses. In this review, we will discuss current epidemiology, prevention, diagnosis, and treatment of the most common causes of viral meningitis and encephalitis worldwide.
RECENT FINDINGS
Viral meningitis and encephalitis are increasingly diagnosed as molecular diagnostic techniques and serologies have become more readily available worldwide but recent progress in novel antiviral therapies remains limited. Emerging and re-emerging viruses that have caused endemic or worldwide outbreaks or epidemics are arboviruses (e.g., West Nile virus, Japanese encephalitis, Tick borne encephalitis, Dengue, Zika, Toscana), enteroviruses (e.g., Enterovirus 71, Enterovirus D68), Parechoviruses, respiratory viruses [e.g., severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, metapneumoviruses, measles, mumps], and herpes viruses [e.g., herpes simplex virus (HSV) type 1 (HSV-1), HSV-2, human herpes (HV) 6, varicella zoster virus (VZV)]. Future efforts should concentrate in increasing availability for those viruses with effective vaccination [e.g., Japanese encephalitis, Tick borne encephalitis, varicella zoster viruses, SARS-CoV-2, influenza], prompt initiation of those with encephalitis with treatable viruses (e.g., HSV-1, VZV), increasing the diagnostic yield by using novel techniques such as metagenomic sequencing and avoiding unnecessary antibiotics in those with viral meningitis or encephalitis.
SUMMARY
We review the current epidemiology, clinical presentation, diagnosis, and treatment of the common causative agents of viral meningitis and encephalitis worldwide.
Topics: Humans; Influenza, Human; COVID-19; SARS-CoV-2; Meningitis, Viral; Viruses; Encephalitis; Herpesvirus 3, Human; Herpesvirus 1, Human; Zika Virus; Zika Virus Infection
PubMed: 37093042
DOI: 10.1097/QCO.0000000000000922 -
Archives of Virology Feb 2021Meningitis is a serious condition that affects the central nervous system. It is an inflammation of the meninges, which is the membrane that surrounds both the brain and... (Review)
Review
Meningitis is a serious condition that affects the central nervous system. It is an inflammation of the meninges, which is the membrane that surrounds both the brain and the spinal cord. Meningitis can be caused by bacterial, viral, or fungal infections. Many viruses, such as enteroviruses, herpesviruses, and influenza viruses, can cause this neurological disorder. However, enteroviruses have been found to be the underlying cause of most viral meningitis cases worldwide. With few exceptions, the clinical manifestations and symptoms associated with viral meningitis are similar for the different causative agents, which makes it difficult to diagnose the disease at early stages. The pathogenesis of viral meningitis is not clearly defined, and more studies are needed to improve the health care of patients in terms of early diagnosis and management. This review article discusses the most common causative agents, epidemiology, clinical features, diagnosis, and pathogenesis of viral meningitis.
Topics: Animals; Humans; Meningitis, Viral; Viruses
PubMed: 33392820
DOI: 10.1007/s00705-020-04891-1 -
American Family Physician Apr 2021Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include... (Review)
Review
Cerebrospinal fluid (CSF) analysis is a diagnostic tool for many conditions affecting the central nervous system. Urgent indications for lumbar puncture include suspected central nervous system infection or subarachnoid hemorrhage. CSF analysis is not necessarily diagnostic but can be useful in the evaluation of other neurologic conditions, such as spontaneous intracranial hypotension, idiopathic intracranial hypertension, multiple sclerosis, Guillain-Barré syndrome, and malignancy. Bacterial meningitis has a high mortality rate and characteristic effects on CSF white blood cell counts, CSF protein levels, and the CSF:serum glucose ratio. CSF culture can identify causative organisms and antibiotic sensitivities. Viral meningitis can present similarly to bacterial meningitis but usually has a low mortality rate. Adjunctive tests such as CSF lactate measurement, latex agglutination, and polymerase chain reaction testing can help differentiate between bacterial and viral causes of meningitis. Immunocompromised patients may have meningitis caused by tuberculosis, neurosyphilis, or fungal or parasitic infections. Subarachnoid hemorrhage has a high mortality rate, and rapid diagnosis is key to improve outcomes. Computed tomography of the head is nearly 100% sensitive for subarachnoid hemorrhage in the first six hours after symptom onset, but CSF analysis may be required if there is a delay in presentation or if imaging findings are equivocal. Xanthochromia and an elevated red blood cell count are characteristic CSF findings in patients with subarachnoid hemorrhage. Leptomeningeal carcinomatosis can mimic central nervous system infection. It has a poor prognosis, and large-volume CSF cytology is diagnostic.
Topics: Central Nervous System Bacterial Infections; Central Nervous System Fungal Infections; Central Nervous System Infections; Central Nervous System Parasitic Infections; Central Nervous System Viral Diseases; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Culture Techniques; Eosinophils; Glucose; Humans; Leukocytes; Lymphocytes; Meningeal Carcinomatosis; Meningitis, Cryptococcal; Neurosyphilis; Neutrophils; Polymerase Chain Reaction; Reference Values; Spinal Puncture; Subarachnoid Hemorrhage; Tuberculosis, Central Nervous System
PubMed: 33788511
DOI: No ID Found -
Neurologic Clinics Feb 2022Infectious meningitis and encephalitis are associated with significant morbidity and mortality worldwide. Acute bacterial meningitis is rapidly fatal and early... (Review)
Review
Infectious meningitis and encephalitis are associated with significant morbidity and mortality worldwide. Acute bacterial meningitis is rapidly fatal and early recognition and institution of therapy are imperative. Viral meningitis is typically a benign self-limited illness. Chronic meningitis (defined as presenting with >4 weeks of symptoms) is most often caused by tuberculosis and fungal infection. Because the diagnostic testing for tuberculous meningitis is insensitive and cultures often take weeks to grow, therapy is often initiated empirically when the diagnosis is suspected. Human simplex virus encephalitis is the most common cause of encephalitis and requires prompt treatment with intravenous acyclovir.
Topics: Acyclovir; Encephalitis; Humans; Meningitis, Bacterial; Meningitis, Viral
PubMed: 34798976
DOI: 10.1016/j.ncl.2021.08.006 -
Biomarkers in Medicine Apr 2020Infectious meningitis can be caused by viral, bacterial or fungal pathogens. Despite widely available treatments, many types of infectious meningitis are still... (Review)
Review
Infectious meningitis can be caused by viral, bacterial or fungal pathogens. Despite widely available treatments, many types of infectious meningitis are still associated with significant morbidity and mortality. Delay in diagnosis contributes to poor outcomes. Cerebrospinal fluid cultures have been used traditionally but are time intensive and sensitivity is decreased by empiric treatment prior to culture. More rapid techniques such as the cryptococcal lateral flow assay (IMMY), GeneXpert MTB/Rif Ultra (Cepheid) and FilmArray multiplex-PCR (Biofire) are three examples that have drastically changed meningitis diagnostics. This review will discuss a holistic approach to diagnosing bacterial, mycobacterial, viral and fungal meningitis.
Topics: Adult; Diagnostic Techniques and Procedures; Humans; Meningitis; Time Factors
PubMed: 32270693
DOI: 10.2217/bmm-2019-0333 -
Immunity Nov 2022The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of...
The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II MM were abundant neonatally, whereas MHC-II MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.
Topics: Animals; Mice; Lipopolysaccharides; Mice, Inbred C57BL; SARS-CoV-2; COVID-19; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Macrophages; Meninges
PubMed: 36323311
DOI: 10.1016/j.immuni.2022.10.005 -
Nature Oct 2022Combination therapy with PD-1 blockade and IL-2 is highly effective during chronic lymphocytic choriomeningitis virus infection. Here we examine the underlying basis for...
Combination therapy with PD-1 blockade and IL-2 is highly effective during chronic lymphocytic choriomeningitis virus infection. Here we examine the underlying basis for this synergy. We show that PD-1 + IL-2 combination therapy, in contrast to PD-1 monotherapy, substantially changes the differentiation program of the PD-1TCF1 stem-like CD8 T cells and results in the generation of transcriptionally and epigenetically distinct effector CD8 T cells that resemble highly functional effector CD8 T cells seen after an acute viral infection. The generation of these qualitatively superior CD8 T cells that mediate viral control underlies the synergy between PD-1 and IL-2. Our results show that the PD-1TCF1 stem-like CD8 T cells, also referred to as precursors of exhausted CD8 T cells, are not fate-locked into the exhaustion program and their differentiation trajectory can be changed by IL-2 signals. These virus-specific effector CD8 T cells emerging from the stem-like CD8 T cells after combination therapy expressed increased levels of the high-affinity IL-2 trimeric (CD25-CD122-CD132) receptor. This was not seen after PD-1 blockade alone. Finally, we show that CD25 engagement with IL-2 has an important role in the observed synergy between IL-2 cytokine and PD-1 blockade. Either blocking CD25 with an antibody or using a mutated version of IL-2 that does not bind to CD25 but still binds to CD122 and CD132 almost completely abrogated the synergistic effects observed after PD-1 + IL-2 combination therapy. There is considerable interest in PD-1 + IL-2 combination therapy for patients with cancer, and our fundamental studies defining the underlying mechanisms of how IL-2 synergizes with PD-1 blockade should inform these human translational studies.
Topics: CD8-Positive T-Lymphocytes; Cell Differentiation; Drug Therapy, Combination; Humans; Interleukin Receptor Common gamma Subunit; Interleukin-2; Interleukin-2 Receptor alpha Subunit; Interleukin-2 Receptor beta Subunit; Lymphocytic Choriomeningitis; Programmed Cell Death 1 Receptor; T Cell Transcription Factor 1
PubMed: 36171288
DOI: 10.1038/s41586-022-05257-0 -
Infection and Drug Resistance 2020Acute community-acquired bacterial meningitis (ABM) in children continues to have high rates of neurological morbidity and mortality despite the overall declining rates... (Review)
Review
Acute community-acquired bacterial meningitis (ABM) in children continues to have high rates of neurological morbidity and mortality despite the overall declining rates of infection attributed to the use of vaccines and intrapartum Group B prophylaxis. Prompt diagnosis and early antibiotic therapy are crucial and should not be delayed to obtain cranial imaging. Differentiating bacterial from viral meningitis continues to be a clinical dilemma especially in patients with previous antibiotic exposure. Clinical models and inflammatory biomarkers can aid clinicians in their diagnostic approach. Multiplex polymerase chain reaction and metagenomic next-generation sequencing are promising tools that can help in early and accurate diagnosis. This review will present the epidemiology of ABM in children, indications of cranial imaging, role of different models and serum biomarkers in diagnosing ABM, and management including the use of adjunctive therapies and methods of prevention.
PubMed: 33204125
DOI: 10.2147/IDR.S240162 -
Current Opinion in Infectious Diseases Jun 2020Varicella zoster virus (VZV) causes varicella, establishes latency, then reactivates to produce herpes zoster. VZV reactivation can also cause central nervous system... (Review)
Review
PURPOSE OF REVIEW
Varicella zoster virus (VZV) causes varicella, establishes latency, then reactivates to produce herpes zoster. VZV reactivation can also cause central nervous system (CNS) disease with or without rash. Herein, we review these CNS diseases, pathogenesis, diagnosis, and treatment.
RECENT FINDINGS
The most common CNS manifestation of VZV infection is vasculopathy that presents as headache, cognitive decline, and/or focal neurological deficits. VZV vasculopathy has also been associated with cerebral amyloid angiopathy and moyamoya syndrome. Rarely, VZV will produce a meningitis, encephalitis, cerebellitis, and myelopathy. Pathogenic mechanisms include direct VZV infection of affected tissue, persistent inflammation, and/or virus-induced hypercoagulability. Diagnosis is confirmed by the temporal association of rash to disease onset, intrathecal synthesis of anti-VZV antibodies, and/or the presence of VZV DNA in CSF. Most cases respond to intravenous acyclovir with corticosteroids.
SUMMARY
VZV produces a wide spectrum of CNS disorders that may be missed as some cases do not have an associated rash or a CSF pleocytosis. Clinicians must be vigilant in including VZV in their differential diagnosis of CNS infections as VZV is a ubiquitous pathogen; importantly, VZV CNS infections are treatable with intravenous acyclovir therapy and corticosteroids.
Topics: Acyclovir; Adrenal Cortex Hormones; Antibodies, Viral; Antiviral Agents; Central Nervous System Infections; Herpes Zoster; Herpesvirus 3, Human; Humans; Meningitis
PubMed: 32332223
DOI: 10.1097/QCO.0000000000000647