Viral Meningitis In Children Research Articles

RNA sequencing reveals differential long noncoding RNA expression profiles in bacterial and viral meningitis in children

BackgroundWe aimed to investigate the involvement of long non-coding RNA (lncRNA) in bacterial and viral meningitis in children.MethodsThe 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.ResultsCompared 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.ConclusionsOur 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.

Epidemiological analysis of viral meningitis in children under 4 years of age in Brazil 2011–2021: Addressing prevalence, disparities, and public health challenges

Epidemiological analysis of viral meningitis in children under 4 years of age in Brazil 2011–2021: Addressing prevalence, disparities, and public health challenges

Clinical and prognostic significance of plasma fibronectin and circulating immune complexes in viral meningitis in children

Clinical and prognostic significance of plasma fibronectin and circulating immune complexes in viral meningitis in children

Epidemiological characteristics and climatic variability of viral meningitis in Kazakhstan, 2014-2019.

The comprehensive epidemiology and impact of climate on viral meningitis (VM) in Kazakhstan are unknown. We aimed to study the incidence, in-hospital mortality and influence of climatic indicators on VM from 2014 to 2019. Nationwide electronic healthcare records were used to explore this study. ICD-10 codes of VM, demographics, and hospital outcomes were evaluated using descriptive statistics and survival analysis. During the 2014-2019 period, 10,251 patients with VM were admitted to the hospital. 51.35% of them were children, 57.85% were males, and 85.9% were from the urban population. Enteroviral meningitis was the main cause of VM in children. The incidence rate was 13 and 18 cases per 100,000 population in 2014 and 2019, respectively. Case fatality rate was higher in 2015 (2.3%) and 2017 (2.0%). The regression model showed 1°C increment in the daily average temperature might be associated with a 1.05-fold (95% CI 1.047-1.051) increase in the daily rate of VM cases, 1hPa increment in the average air pressure and 1% increment in the daily average humidity might contribute to a decrease in the daily rate of VM cases with IRRs of 0.997 (95% CI 0.995-0.998) and 0.982 (95% CI 0.981-0.983), respectively. In-hospital mortality was 35% higher in males compared to females. Patients residing in rural locations had a 2-fold higher risk of in-hospital death, compared to city residents. Elderly patients had a 14-fold higher risk of in-hospital mortality, compared to younger patients. This is the first study in Kazakhstan investigating the epidemiology and impact of climate on VM using nationwide healthcare data. There was a tendency to decrease the incidence with outbreaks every 5 years, and mortality rates were higher for Russians and other ethnicities compared to Kazakhs, for males compared to females, for elder patients compared to younger patients, and for patients living in rural areas compared to city residents. The climatic parameters and the days of delay indicated a moderate interaction with the VM cases.

Investigating the mechanism of Echovirus 30 cell invasion.

Viruses invade susceptible cells through a complex mechanism before injecting their genetic material into them. This causes direct damage to the host cell, as well as resulting in disease in the corresponding system. Echovirus type 30 (E30) is a member of the Enterovirus B group and has recently been reported to cause central nervous system (CNS) disorders, leading to viral encephalitis and viral meningitis in children. In this review, we aim to help in improving the understanding of the mechanisms of CNS diseases caused by E30 for the subsequent development of relevant drugs and vaccines.

Результаты рандомизированного исследования по оценке терапевтической эффективности интерферона α-2b в комплексной терапии вирусных менингитов у детей

Objective. To evaluate the therapeutic efficacy and safety of the drug Viferon®, rectal suppositories (RS) in the complex therapy of viral meningitis (VM) based on the dynamics of clinical and laboratory parameters in children. Patients and methods. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the therapeutic efficacy and safety of the drug Viferon® (recombinant interferon α-2b) in the complex therapy of VM in children. The study included 140 children from 2 to 18 years old, who made up two groups: group 1 (n = 70) received CP Viferon® in age doses: up to 3 years – 500.000 IU; from 4 to 11 years – 1.000.000 IU; from 12 to 18 years – 3.000.000 IU each. Viferon® was prescribed 1 suppository 2 times a day for 7 days, then 1 time a day for 7 days. The 2nd group (n = 70) consisted of children with VM who received placebo, RS according to the scheme of the Viferon®.The children were randomized by gender, age, weight and severity of the VM. The effectiveness of therapy was evaluated based on the duration of clinical symptoms, the dynamics of pleocytosis and rehabilitation of cerebrospinal fluid (CSF) on day 15, the frequency of complete recovery on day 15, after 1, 3 and 6 months. The safety of using of the Viferon® was assessed according to the state of clinical and laboratory parameters, frequency and severity of adverse events. Results. The etiology of VM was determined in 64.3% of cases (n = 90) and included herpes viruses 1, 2, 3, 4, 5, 6 type, interoviruses, tick-borne encephalitis virus. It was found that children of group 1 had significantly shorter duration of meningeal, cerebral and intoxication syndromes, approximately 2 times less pleocytosis on day 15 and CSF sanitation from viruses in all cases, unlike patients of group 2 (p < 0.001). The differences with group 2 were also significant in age subgroups. Patients receiving the Viferon® were more likely to achieve complete clinical recovery on day 15 and did not have a residual deficiency in the outcome in 100% of cases after 3 months. The use of the Viferon® turned out to be safe, did not increase the incidence of the adverse events compared with the 2nd group of children receiving placebo. Conclusion. The use of the Viferon® in children with VM according to the scheme developed by the authors significantly reduces the regression of inflammatory changes and the timing of CSF rehabilitation, the duration of the main clinical symptoms compared with the placebo group, leads to recovery in 100% of cases. Key words: viral meningitis, therapy, interferon-alpha2b, children

A semiparametric approach for meta-analysis of diagnostic accuracy studies with multiple cut-offs.

The accuracy of a diagnostic test is often expressed using a pair of measures: sensitivity (proportion of test positives among all individuals with target condition) and specificity (proportion of test negatives among all individuals without target condition). If the outcome of a diagnostic test is binary, results from different studies can easily be summarized in a meta-analysis. However, if the diagnostic test is based on a discrete or continuous measure (e.g., a biomarker), several cut-offs within one study as well as among different studies are published. Instead of taking all information of the cut-offs into account in the meta-analysis, a single cut-off per study is often selected arbitrarily for the analysis, even though there are statistical methods for the incorporation of several cut-offs. For these methods, distributional assumptions have to be met and/or the models may not converge when specific data structures occur. We propose a semiparametric approach to overcome both problems. Our simulation study shows that the diagnostic accuracy is under-estimated, although this underestimation in sensitivity and specificity is relatively small. The comparative approach of Steinhauser et al. is better in terms of coverage probability, but may lead to convergence problems. In addition to the simulation results, we illustrate the application of the semiparametric approach using a published meta-analysis for a diagnostic test differentiating between bacterial and viral meningitis in children.

The cerebrospinal fluid neutrophil to lymphocyte ratio is a sensitive biomarker for bacterial meningitis in children.

The cerebrospinal fluid neutrophil-to-lymphocyte ratio (CSF NLR) as a diagnostic biomarker of bacterial meningitis has been reported in adult trials. The aim of this study was to evaluate the CSF NLR as a diagnostic biomarker of bacterial meningitis in children and to define an optimal CSF NLR concentration. We performed a retrospective cohort study of children with clinical findings compatible with meningitis. CSF NLR was calculated as the ratio of neutrophil count to lymphocyte count in cerebrospinal fluid (CSF). Initial data included clinical, radiological, and laboratory diagnostics. We determined CSF parameters from children with infectious meningitis (n = 348) and subdivided them into bacterial meningitis (n = 112) and viral meningitis (n = 236). CSF NLR was significantly higher in bacterial meningitis than in viral meningitis (P < 0.001), and its level was higher in Gram-negative bacterial infections than in Gram-positive bacterial infections (P = 0.01). In the receiver operating characteristic curve analysis, CSF NLR was better than CSF protein/sugar/WBC in the ability to distinguish bacterial meningitis from viral meningitis (AUC 0.91 ± 0.02 versus 0.88 ± 0.03/0.87 ± 0.03/0.86 ± 0.03), and using a cutoff point of 0.68, the sensitivity was 0.90, and the specificity was 0.75. Compared with Gram-positive infection, CSF NLR with Gram-negative infection was higher (media, IQR (1.18 (0.19-2.33) versus 3.90 (1.50-8.91), P = 0.01). CSF NLR is a more useful diagnostic tool to distinguish between bacterial meningitis and viral meningitis in children. While at a cutoff value of 0.68, CSF NLR has better sensitivity and specificity for bacterial meningitis, and the higher level of CSF NLR could be related to Gram-negative bacterial infection.

The Prevalence of Viruses in the Cerebrospinal Fluid of Children with Aseptic Meningitis in Shiraz, Iran

Objectives: The current study aimed to evaluate the causative agents of viral meningitis through real-time PCR among children with aseptic meningitis. Methods: Children aged 1 month to 16 years with suspected viral meningitis were enrolled in this study (March 2014-February 2015). Cerebrospinal fluid samples were analyzed by real-time PCR for detection of enterovirus, mumps, measles, adenovirus, EBV, CMV, VZV, hhv 6, and rubella viruses. Demographic information, laboratory data, and clinical presentations of patients were also collected. Results: Of 56 patients suspected to viral meningitis, 21 (38.9 %) had a positive PCR result. Enterovirus (42.85%) and mumps (38.1%) were the most prevalent viruses, and VZV and measles were not detected. Three children were coinfected with enterovirus/hhv6, enterovirus/EBV, and mump/adenovirus. Fever, headache, and nausea/vomiting were the most common symptoms in children. The rates of symptoms were not statistically significant among children with positive and negative PCR tests. Conclusions: In the present study Enterovirus and mumps viruses were the most common causes of viral meningitis in children. PCR, as a rapid test for the diagnosis of viral meningitis, can be used to decrease hospitalization length.

To LP or not to LP? Identifying the Etiology of Pediatric Meningitis.

Introduction of conjugate vaccines against Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis has led to a substantial reduction in cases of acute bacterial meningitis in countries with high routine childhood immunization coverage. The majority of children hospitalized with meningitis in high-income countries have viral or aseptic meningitis and do not require antibiotic treatment. Cerebrospinal fluid analysis is irreplaceable in appropriately diagnosing and treating bacterial meningitis and avoiding unnecessary antibiotics and prolonged hospitalizations in children with viral meningitis. New diagnostic tests have improved detection of bacterial and viral pathogens in cerebrospinal fluid, underscoring the importance of promptly performing lumbar puncture when meningitis is suspected. This article provides an overview of acute bacterial and viral meningitis in children, focusing on the changing epidemiology, the advantages and limitations of conventional and newer diagnostic methods, and considerations for clinical practice.

Cerebrospinal Fluid Lactate Concentration to Differentiate Bacterial from Viral Meningitis in Children

Ton Nu van Anh1*, Nguyen Huu Son2, Mai Thi Hien Uyen2, Nguyen Thi Diem Chi2, Nguyen Thi Hong Duc2 and Tran Vinh Phu1 Author Affiliations 1Pediatric Department, Hue University of Medicine and Pharmacy, Vietnam 2Pediatric Center, Hue Central Hospital, Vietnam Received: February 26, 2019 | Published: March 12, 2019 Corresponding author: Ton Nu van Anh, Pediatric Department, Hue University of Medicine and Pharmacy, Vietnam DOI: 10.26717/BJSTR.2019.15.002769 Also View In:

Enterovirus serotypes in patients with central nervous system and respiratory infections in Viet Nam 1997\u20132010

BackgroundEnteroviruses are the most common causative agents of human illness. Enteroviruses have been associated with regional and global epidemics, recently, including with severe disease (Enterovirus A71 and D68), and are of interest as emerging viruses. Here, we typed Enterovirus A-D (EV) from central nervous system (CNS) and respiratory infections in Viet Nam.MethodsData and specimens from prospective observational clinical studies conducted between 1997 and 2010 were used. Species and serotypes were determined using type-specific RT-PCR and viral protein 1 or 4 (VP1, VP4) sequencing.ResultsSamples from patients with CNS infection (51 children – 10 CSF and 41 respiratory/rectal swabs) and 28 adults (28 CSF) and respiratory infection (124 children – 124 respiratory swabs) were analysed. Twenty-six different serotypes of the four Enterovirus species (A-D) were identified, including EV-A71 and EV-D68. Enterovirus B was associated with viral meningitis in children and adults. Hand, foot and mouth disease associated Enteroviruses A (EV-A71 and Coxsackievirus [CV] A10) were detected in children with encephalitis. Diverse serotypes of all four Enterovirus species were found in respiratory samples, including 2 polio-vaccine viruses, but also 8 CV-A24 and 8 EV-D68. With the exception of EV-D68, the relevance of these viruses in respiratory infection remains unknown.ConclusionWe describe the diverse spectrum of enteroviruses from patients with CNS and respiratory infections in Viet Nam between 1997 and 2010. These data confirm the global circulation of Enterovirus genera and their associations and are important for clinical diagnostics, patient management, and outbreak response.

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children

ObjectiveTo assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis (BM) from viral meningitis (VM) in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. MethodsChildren with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. ResultsAt a cut‐off value of 3mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between BM and VM, the area under the curve (AUC) for CSF lactate was 0.979. ConclusionsThe authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut‐off value of 3mmol/L, CSF lactate has high diagnostic accuracy for BM, mean levels in VM remain essentially below 2mmol/L.

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children

ObjectiveTo assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. MethodsChildren with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. ResultsAt a cut-off value of 3mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. ConclusionsThe authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2mmol/L.

Etiology and prognosis of acute viral encephalitis and meningitis in Chinese children: a multicentre prospective study

BackgroundIn China, there were few studies about the pathogens of acute viral encephalitis and meningitis in children in recent years. The aims of this study were to characterize the etiology and prognosis of acute viral encephalitis and meningitis in Chinese children.MethodsThis was a multicentre prospective study. Two hundred and sixty one viral encephalitis patients and 285 viral meningitis patients were enrolled. The mean age of viral encephalitis and meningitis were 5.88 ± 3.60 years and 6.39 ± 3.57 years, respectively. Real-time reverse transcription PCR and multiplex PCR were used to detect human enteroviruses and herpes viruses in cerebrospinal fluid (CSF) of patients with encephalitis or meningitis. The enzyme-linked immune absorbent assay (ELISA) was used for detecting IgM antibody against Japanese encephalitis virus (JEV) in CSF and against mumps virus, tick-borne encephalitis virus (TBEV), dengue virus and rubella virus in acute serum. The clinical and outcome data were collected during patients’ hospitalization.ResultsThe etiology of viral encephalitis was confirmed in 52.5% patients. The primary pathogen was human enteroviruses (27.7%) in viral encephalitis. The incidence of sequelae and the fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The etiology of viral meningitis was identified in 42.8% cases. The leading pathogen was also human enteroviruses (37.7%) in viral meningitis. The prognosis of viral meningitis was favorable with only 0.7% patients had neurological sequelae.ConclusionsHuman enteroviruses were the leading cause both in acute viral encephalitis and viral meningitis in children. The incidence of sequelae and fatality rate of viral encephalitis with confirmed etiology were 7.5% and 0.8%, respectively. The prognosis of viral meningitis was favorable compared to viral encephalitis.

Etiological agents of viral meningitis in children from a dengue-endemic area, Southeast region of Brazil

Meningitis is a disease with a global distribution that constitutes a worldwide burden, with viruses as the primary etiologic agents. The range of viral meningitis severity depends mainly on age, immune status and etiological agent. The aim of this work was to investigate the suspected cases of viral meningitis using molecular techniques to confirm the viral infection. The diagnosed virus was correlated with clinical findings and cytochemical parameters in cerebrospinal liquid (CSF) of patients. CSF of 70 children with the presumptive diagnosis of viral meningitis was analyzed by real time PCR (qPCR). Viruses were identified by qPCR in 44 CSF samples (62.9%). Among them, 31 were identified as Enterovirus (ENTV) (70.4%), six as Human herpes virus 3 (HHV-3) (13.6%), five as Dengue virus (DENV) (11.7%), one as Human herpes virus 1–2 (2.3%) and one as Human herpes virus 5 (2.3%). Patients in the HHV-positive groups had increased percentage of polymorphonuclear neutrophils (PMN) (mean of 81%) while the groups of patients with DENV and ENTV had a mean of 30.9%.This study contributes to the knowledge of the epidemiological distribution of viral agents in CNS infections in children. In addition, it raises the relevance of DENV as an agent of CNS infection, and reinforces the importance for molecular in the cases of CNV infection.

Clinical value of indicators of cationic proteins, leukocytes myeloperoxidase and fibronectin blood plasma in viral meningitis in children

Objective : was to establish clinical and diagnostic value of cytochemical indices of peripheral blood leukocytes (cationic protein and myeloperoxidase), fibronectin blood plasma to assess the severity, predict the course and outcome of viral meningitis in children. Subjects and methods. In 450 patients with viral meningitis (enterovirus, arbovirus, parotitic, herpesviral, adenovirus etiology) at the age of 14 years, the parameters of the microbicidal system of leukocytes (cation proteins, myeloperoxidase) and fibronectin blood plasma were determined. Etiological diagnosis of meningitis was confirmed by release of viral RNA from blood and cerebrospinal fluid by the polymerase chain reaction, enzyme-linked immunosorbent assay (ELISA). The results and conclusion. Found that severe, prolonged duration, lethal outcome of viral meningitis in children are accompanied by sugnificant suppression of cationic proteins, myeloperoxidase, fibronectin blood plasma, maximally expressed in lethal outcomes, compared with the severe form, but with a favorable outcome and control. Settings imbalance cationic proteins, myeloperoxidase, fibronectin blood plasma are objective criteria of the adaptation syndrome that reflects the state of the phagocytosis system in viral meningitis in children and can be considered as additional criteria for predicting the course and outcome of disease.

THE CLINICAL SIGNIFICANCE OF THE CYTOKINE STATUS OF BLOOD SERUM IN VIRAL MENINGITIS IN CHILDREN

The determination of cytokines in blood serum in 450 patients under the age of 14 years old with viral meningitis (VM) of different etiologies. In severe forms of VM the increase in IL-1b,IL-6, IL-8, TNF-a and decreased concentration of IL-2, INF-a, INF-g, compared to the level of the relevant indicators in the diseases of moderate severity and the norm. The revealed changes in cytokine regulation persisted into the period of convalescence, accompanied by stimulation of INF-a, INF-g and suppression of IL-2. Patients with a prolonged course of VM, a reduction in IL-8, INF-a, IL-1b and increase of INF-a and INF-g in serum, which may indicate a slow regression of the inflammatory process. Patients with fatal outcome was determined a significantly higher level of IL-6, INF-g in comparison with similar indicators of a severe form of VM, but with a favorable outcome. The settings in the content of cytokines in blood serum can be used in clinical practice to predict the course and outcomes of VM in children.

Hospital admissions for viral meningitis in children in England over five decades: a population-based observational study

A substantial reduction in bacterial meningitis has occurred in the UK following successful implementation of immunisation programmes. Most childhood meningitis in developed countries is now caused by viruses. Long-term trends in paediatric viral meningitis in England have not previously been reported. The objective of this study is to report on epidemiological trends over time in childhood viral meningitis in England. In this population-based observational study, we used routinely collected hospital discharge records from English National Health Service hospitals from 1968-2011 to analyse annual age-specific admission rates for viral meningitis, including specific viral aetiologies, in children younger than 15 years. We analysed hospital discharge records from Jan 1, 1968, to Dec 31, 2011. Hospital admission rates for viral meningitis from Jan 1, 1968, to Dec 31, 1985, varied annually, with a mean of 13·5 admissions per 100 000 children aged less than 15 years, per year (95% CI 13·0-14·0). Admission rates declined during the late 1980s, and the mean number of admissions from 1989-2011 was 5·2 per 100 000 per year (5·1-5·3). This decrease was entirely in children aged 1-14 years. Admission rates for infants aged less than 1 year increased since 2005, to 70·0 per 100 000 (63·7-76·2) in 2011, which was driven by an increase in admission of infants aged 90 days or less. In 1968-85, the majority of cases in children were in those aged 1-14 years (22 150 [89%] of 24 920 admissions). In 2007-11, 1716 (72%) of 2382 cases were in infants. Admissions for mumps-related meningitis almost disappeared following introduction of the measles-mumps-rubella (MMR) vaccine in 1988. Admissions with a specified viral aetiology have increased since 2000. Trends in viral meningitis admissions have changed substantially over the past 50 years, and probably reflect the impact of the MMR vaccine programme and the use of more sensitive diagnostic techniques. None.

Cerebrospinal fluid ferritin and albumin index: potential candidates for scoring system to differentiate between bacterial and viral meningitis in children

Objectives: To evaluate the diagnostic role of cerebrospinal fluid (CSF) ferritin and albumin index (AI = CSF albumin/serum albumin × 1000) in differentiating acute bacterial meningitis (ABM) from acute viral meningitis (AVM) in children.Methods: The study included 42 cases each of ABM and AVM in pediatric age group. Receiver operating characteristic (ROC) analysis was carried out for CSF ferritin and AI. Binary logistic regression was also done.Results: CSF ferritin and AI were found significantly higher in ABM compared to AVM. Model obtained using AI and CSF ferritin along with conventional criteria is better than existing models.