Aseptic Meningitis In Children Research Articles

Enteroviral meningitis in children: Clinical and laboratory features with and without pleocytosis.

Enteroviruses (EV) are most common causes of the etiologically known aseptic meningitis in children. EV can be detected with polymerase chain reaction (PCR) in cerebrospinal fluid (CSF) samples. We aimed to evaluate the clinical and laboratory characteristics of children diagnosed with PCR-confirmed EV meningitis in CSF samples. Patients aged 1 month to 17 years who underwent lumbar puncture (LP) with suspected meningitis and had CSF viral PCR and culture results between September 2012 and January 2021 at a tertiary care hospital in Turkey were included. Patients with no virus detected in CSF samples by PCR was comprised PCR-negative group. The EV PCR-positive patients were divided into two groups based on CSF pleocytosis as enteroviral meningitis (EVM) with CSF pleocytosis and EVM without CSF pleocytosis, and compared in terms of clinical and laboratory features. 78 (38.2%) were EV PCR-positive, and 126 (61.8%) were PCR-negative. Pleocytosis was detected in 55 (70.5%) EV PCR-positive patients and 94 (74.6%) of PCR-negative patients. Convulsion was significantly frequent (p=0.017) in EV PCR-positive patients with no pleocytosis. Protein and lactate concentrations in CSF were significantly higher in EV PCR-positive patients with pleocytosis (p=0.048, p=0.001, respectively). Median hospital stay was significantly longer in PCR-negative group (p<0.001). Diagnosing EVM with PCR prevents long-term hospitalization, unnecessary antibiotic use and healthcare-related complications.

Molecular Genotyping of Circulating Enterovirus in the Lazio Region from 2012 to 2023.

Enteroviruses (EVs) are ubiquitous viruses that circulate worldwide, causing sporadic or epidemic infections, typically during the summer and fall. They cause a broad spectrum of illnesses, ranging from an unspecified febrile clinical presentation to a severe illness. EVs are recognized to be the most frequent etiological agents of aseptic meningitis in children. However, as the infection is usually mild and self-limiting, it remains underestimated, and the epidemiology of EVs is poorly understood. To date, no vaccine or effective therapy for all types of enteroviruses is available, and EVs constitute a public health concern. Here, we investigated the molecular epidemiology of EV strains circulating in the Lazio region over a 10-year time span (2012-2023) by using a sequence-typing approach and phylogenetic analysis. The epidemiological trend of EV infection has undergone changes during the SARS-CoV-2 pandemic (2020-2021), which resulted in a modification in terms of the number of diagnosed cases and seasonality. From 2022, the circulation of EVs showed a behavior typical of the pre-pandemic period, although changes in predominantly circulating strains have been noted. Both epidemic and sporadic circulation events have been characterized in the Lazio region. Further analyses are needed to better characterize any strain with higher potential pathogenic power and to identify possible recombinant strains.

Metatranscriptomics revealed the molecular characterization of circulating enterovirus strains causing aseptic meningitis in children in Wuxi, China

Enteroviruses are major etiological agents of aseptic meningitis globally, however information on circulating enterovirus types associated with this disease in Wuxi, China is limited. In this study, cerebrospinal fluid samples were collected from 20 pediatric aseptic meningitis cases in a Wuxi hospital in 2020 and subjected to metagenomic analysis to detect pathogens. Enterovirus B was detected in 9 cases, including 7 echovirus 18 (E18) and 2 echovirus 11 (E11) strains. The E18 strains exhibited 87.5–98.2% nucleotide identity and phylogenetically clustered with other China E18 strains, while the E11 strains showed 97.59% identity and clustered within the D5 subgroup along with other China E11 strains. One E18 strain was identified as a novel recombinants with a distinct recombination breakpoint within 3D gene. These findings expand knowledge on enteroviruses associated with pediatric aseptic meningitis in Wuxi, and highlight the circulation of genetically diverse E18 and E11 strains, including novel E18 recombinants. Characterization of enterovirus diversity by metagenomic analysis is important for molecular diagnosis and epidemiological tracking of aseptic meningitis cases. Continued surveillance of circulating enterovirus strains in Wuxi that may cause future outbreaks is warranted.

Impact of the COVID-19 Outbreak on Aseptic Meningitis in Children.

Viruses are the most common infectious causes of aseptic meningitis (AM). After the COVID-19 pandemic, AM following the COVID-19 disease and its different vaccines were reported. This study compares some characteristics of patients with AM before and after the COVID-19 pandemic. This retrospective cross-sectional study analyzed patients' demographic and laboratory data (one month to 14 years old) with AM from March 2018 to March 2022. The first period involves two years before the COVID-19 outbreak (March 2018 to March 2020). The second period starts with the COVID-19 pandemic (from March 2020 until March 2022). A significant decrease was observed in the frequency of patients admitted with AM after the COVID-19 pandemic in the referral children's hospital in Qazvin. The incidence of AM in children older than five decreased significantly, and as a result, the average age of patients with this diagnosis decreased, too. A meaningful decline in the prevalence of AM in the summer and fall seasons has been observed. After the COVID-19 outbreak, the incidence of AM in children significantly decreased. Implementing the hygienic recommendations for inhibiting COVID-19 virus transmission also protected children from the spread of other viruses.

Study of CSF C-Reactive Protein for the Differentiation of Bacterial Meningitis from Aseptic Meningitis in Children

Background: Acute meningitis is a major cause of death, and disability worldwide. Differentiating bacterial from nonbacterial meningitis is very important in deciding on treatment. Bacterial meningitis is a life-threatening neurological condition, and needs prompt parenteral antibiotics, compared to viral, and aseptic meningitis which carries relatively better outcomes. Objective: To identify the importance of Cerebrospinal fluid C- reactive protein (CSF-CRP) to establish the diagnosis of ABM. Method: This study was conducted from 01 January 2017 to 30th June 2017 at the indoor department of Pediatric Medicine at Bangladesh Sishu Hospital &amp; Institute (BSH &amp; I) to the measure of CSF C-Reactive protein for the differentiation of bacterial meningitis from aseptic meningitis in children. One hundred patients had participated after meeting the inclusion, and exclusion criteria. Patients were selected by purposive sampling. Ethical clearance was obtained from the National Health Research Ethics Committee, BangladeshShishu Hospital&amp; Institute, Dhaka. Results: Out of 57 cases of bacterial meningitis, 22 cases were culture-negative, and 35 cases were culture-positive. 22 cases (62.85%) out of 35 cases culture positive were Streptococcus Pneumoniae followed by 08 cases (22.85%) were Neisseria Meningitis, Haemophilus Influenza 3 cases (8.57%), E.coli were 02 cases (5.71%). WBC count &amp; PMN (%) were increased significantly in bacterial meningitis, compared to aseptic meningitis. Protein and glucose levels in CSF were not significantly different between bacterial meningitis, and the aseptic meningitis group (Table 2). In the case of bacterial meningitis, in 51(89.47%) cases out of 57, the CSF CRP test was truly positive, mean±SD 21.7±10.9, and false negative were only 6 cases (10.52%). In aseptic meningitis 39 cases (90.69%) out of 43 cases, the CSF-CRP test was truly negative, and false positives were 04 cases (9.30%). (Table-4) shows outcome in the meningitis group showed .....

Molecular Detection of Leptospira in Pediatric Aseptic Meningitis

Leptospirosis is a zoonotic disease caused by pathogenic Leptospira bacterial species. It is tremendously neglected, and scarce epidemiological data is present worldwide. Aseptic meningitis is a rare secondary manifestation of Leptospira infection. Molecular detection of leptospira DNA in cerebrospinal fluid (CSF) samples of children younger than two years is could be considered for diagnosis of aseptic meningitis. A total of 50 CSF samples suspected of aseptic meningitis were collected from pediatric patients (<2 years) presenting to Omdurman Teaching Hospital in Khartoum state, Sudan, between June and September 2018. PCR was used to investigate the presence of leptospira DNA in these samples. Out of the 50 CSF samples in our study, two samples (4%) tested positive for Leptospira DNA using PCR. Leptospira is an overlooked cause of aseptic meningitis in children, and PCR can be used for its diagnosis. J Microbiol Infect Dis 2022; 12(1):35-37.

Aseptic meningitis in children: seasonal variation and diagnostic problems as reflected in the authors’ experiences from 2017–2018

Meningitis is the most common infectious disease of the central nervous system both in children and in adults. The incidence of the disease in Poland, similar to Western Europe, is 6–8 cases per 100,000/year, with the highest figure for children up to 4 years of age. Aim of the study: The aim of the study was to make a detailed analysis of aseptic meningitis cases in children, with a focus on aetiology and course of the disease, and laboratory results. Materials and methods: A retrospective analysis was performed on a group of 59 children aged between 2.5 months and 17 years in whom aseptic meningitis was diagnosed based on clinical evaluation. Results: Between May and October 2018, 44 children aged 7.99 ± 3.93 were hospitalised with the diagnosis of nonpyogenic (aseptic) meningitis. In 9 patients (20.5%), enteroviral neurological infection was found, and in 8 (18.2%) Borrelia burgdorferi, in 5 (11.3%) EBV and in 2 (4.5%) HHV-7 neurological infection was diagnosed. For 20 children (45.5%), the cause of infection could not be established. The longest hospitalisation time was associated with Lyme neuroborreliosis. In the same months of 2017, 15 patients were hospitalised at our department with aseptic meningitis. The numbers of cases for different causes were: undetermined – 9 patients (60%), enteroviral – 2 (13%), EBV – 2 (13%), Parvovirus B19 – 1 patient (7%) and VZV – 1 patient (7%). Conclusions: In 2018, a threefold increase was observed in the number of hospitalisations associated with aseptic meningitis in relation to the same period of 2017, with a lasting predominance of boys. Most frequently, the aetiology was undetermined. Among the cases in which the cause was established, the most common aetiology was enteroviral. In 2018, unlike in 2017, cases of hospitalisation for neuroborreliosis were recorded. Incomplete utilisation of the polymerase chain reaction method was considered to be one of the causes of insufficient identification of neurotropic pathogens. A general examination of the cerebrospinal fluid did not differentiate between causes of aseptic meningitis.

Analysis of enterovirus genotypes in the cerebrospinal fluid of children associated with aseptic meningitis in Liaocheng, China, from 2018 to 2019

BackgroundAseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng.MethodsWe reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease.ResultsA total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region.ConclusionsThis study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.

Severity of parechovirus infections in infants under 3 months of age and comparison with enterovirus infections: A French retrospective study

While enteroviruses (EV) are a well-recognized cause of aseptic meningitis in children, human parechoviruses (HPeV), especially genotype 3, have been increasingly reported as a frequent cause of sepsis-like illness and meningitis among young infants. The aim of this study was to describe the epidemiological, clinical, and laboratory characteristics of HPeV infections in infants and to compare them with those of well-known EV infections. This monocentric retrospective study was carried out at the pediatric unit of Nantes University Hospital from January 2015 to August 2018. All patients under 18 years of age with diagnosis codes referring to fever, for whom viral infection was suspected and cerebrospinal fluid (CSF) specimens were collected, were included. All CSF specimens were screened by duplex real-time polymerase chain reaction (PCR) assay that allows for the simultaneous detection of EV and HPeV in clinical samples. During the study period, 1373 CSF specimens from patients under 18 were included. A total of 312 CSF samples were positive for HPeV (n=34) or EV (n=278). Among the 34 HPeV-positive patients, 97% (33/34) were under 3 months of age, whereas the rate was 54% (149/278) for EV-positive patients (P<0.001); thus, patients under 3 months of age were defined as the study population for the rest of this work. A review of the medical records was carried out for the positive cases. In this population, the HPeV detection rate was 5.6% versus 25.3% (P<0.001) for EV. All but one of the HPeV samples available for genotyping were HPeV-3. No seasonality was observed for HPeV infections. Length of hospital stay tended to be longer for children infected with HPeV compared with those infected by EV (3 days vs. 2 days, P=0.05). Clinicians reported more severe illness presentations among HPeV-infected infants, with more frequent administration of fluid bolus (P<0.02). Regarding laboratory characteristics, a significant lack of cellular reaction in the CSF (P=0.004) as well as lower C-reactive protein (CRP) levels (P=0.006) and neutrophil counts (P<0.001) were noted for HPeV infections compared with EV infections. Our results confirm the early onset of HPeV infections (more than 95% of patients aged under 3 months). The clinical presentation and laboratory characteristics of the two infections was similar. However, some higher clinical severity criteria and a lack of CSF pleocytosis were regularly observed in patients with HPeV infections. Considering the significant proportion (5.6%; 95% CI, 3.7–7.5) of all CSF samples in our series, HPeV detection should be systematically included in the microbiological diagnosis of febrile children under 3 months of age.

Clinical Prediction Rule for Distinguishing Bacterial From Aseptic Meningitis.

New biomarkers like procalcitonin and C-reactive protein may help design an accurate decision support tool used to identify children with pleocytosis at low or high risk of bacterial meningitis. Our objective was to develop and validate a score (that we call the meningitis score for emergencies [MSE]) to distinguish bacterial meningitis from aseptic meningitis in children with pleocytosis when initially evaluated at the emergency department. We included children between 29 days and 14 years old with meningitis admitted to 25 Spanish emergency departments. A retrospective cohort from between 2011 and 2016 was used as the derivation set and a prospective cohort recruited during 2017 and 2018 was used as the validation set. Among the 1009 patients included, there were 917 cases of aseptic meningitis and 92 of bacterial meningitis. Using multivariable logistic regression analysis, we identified the following predictors of bacterial meningitis from the derivation set: procalcitonin >1.2 ng/mL, cerebrospinal fluid (CSF) protein >80 mg/dL, CSF absolute neutrophil count >1000 cells per mm3, and C-reactive protein >40 mg/L. Using the derivation set, we developed the MSE, assigning 3 points for procalcitonin, 2 points for CSF protein, and 1 point for each of the other variables. An MSE ≥1 predicted bacterial meningitis with a sensitivity of 100% (95% confidence interval [CI]: 95.0%-100%), a specificity of 83.2 (95% CI: 80.6-85.5), and a negative predictive value of 100% (95% CI 99.4-100.) CONCLUSIONS: The MSE accurately distinguishes bacterial from aseptic meningitis in children with CSF pleocytosis.

The Value of Cerebrospinal Fluid Polymerase Chain Reaction Test in the Diagnosis of Enteroviral Meningitis in Children

Abstract: Background: Non-polio enteroviruses (EVs) are emerged as the most common pathogens of aseptic meningitis in children. In this study we aimed to evaluate clinical, laboratory, cerebrospinal fluid (CSF) findings and the usefulness of CSF EV polymerase chain reaction on management of pediatric patients diagnosed as EV aseptic meningitis. Material-methods:This study included the pediatric patients with aseptic meningitis between January 2014 and January 2016. Results: A total of 23 patients (69.5% boys) diagnosed with EV aseptic meningitis with a median age of 57 months old (range; 1-168 months) were included. The most common months of the patients' admission to hospital were July and May. The most common clinical complaints were womiting (77.2%), fever (73.9%), headache (59%), neck stiffness (36.3%), seizure (22.7%) and altered consciousness (22.7%). CSF pleocytosis was observed in 16 (69.5%) patients and the median CSF white blood cell (WBC) count was 50 cells/mm3 ranged from 0 to 500 cells/mm3. It was found that, CSF cell count was significantly increased with age (p=0.02), whereas acute phase reactant levels and CSF biochemical components were statistically similar according to age (p&amp;gt;0.05). Median duration for hospitalization was 6 days (range: 1-28 days). Eight patients (34.7%) did not receive any antibiotics. Conclusion: Absence of pleocytosis may be a diagnostic challange in very young infants with aseptic meningitis and CSF cell count significantly increases with age. By using rapid EV-PCR assays in the initial diagnosis of aseptic meningitis, the unnecessary usage of antibiotics in viral meningitis can be reduced and also the duration of hospitalization can be shortened.

Diagnosis of aseptic meningitis in children

Diagnosis of aseptic meningitis in children

Clinical presentations, Laboratory analysis and Linear Growth in 50 Neonates and Young Infants with Acute Meningitis: One Year Experience of a Single Center in Qatar.

BackgroundMeningitis frequently occurs in neonates and can lead to a number of acute, severe complications and long-term disabilities. Although, long term growth delay and abnormal weight gain appear to be risk factors following an acute attack of both bacterial and aseptic meningitis in children, especially during the fast phase of infantile growth, the long-term effects of acute meningitis occurring during the neonatal and early infantile periods on linear growth (length, weight and head growth) have not fully reported.Aim of the studyThe objective of this study is to describe the clinical presentation of neonates and young infants with acute meningitis with different etiologies and to determine the clinical impact of the effect of acute meningitis on growth parameters.Material and methodsWe analyzed the clinical data and the growth parameters of 50 newborns and young infants (age: 1.6 ± 0.9 months) admitted to our hospital (Al Wakhra Hospital, Department of Pediatrics, Doha, Qatar), between 1-1-2016 to 1-1-2017, with acute meningitis. Anthropometric measurements included weight, length, and head circumference. Length SDS (L-SDS) and body-mass-index (BMI) were calculated and recorded at every clinic visit, every 3 months for 8 ± 2 months.ResultsIn this age group of neonates and young infants with acute meningitis fever (84%) and hypoactivity (64%) were the major presenting manifestations. Acute bacterial meningitis (n: 10) was associated with higher morbidity [shock (n: 1), subdural empyema (n: 1) and hydrocephalus (n: 1)]. Cerebrospinal fluid (CSF) examinations showed that infants with bacterial meningitis had significantly higher pleiocytosis of mainly polymorphic leukocytes and protein levels, compared to those with aseptic meningitis.All infants showed normal linear growth and weight gain during the follow-up period (8 ± 2 months). The annualized growth rate of infants was 25.3 ± 3.5 cm per year. All had normal length standard deviation scores (LSDS) (−0.2 ± 0.9) and none of them had LSDS < −2. All infants had a normal BMI (16.7 ± 1.8 kg/m2). Head circumference growth was normal in 49/50 infants (43.8 ± 1.8 cm) at 8 ± 2 months. One infant developed hydrocephalus after group B streptococcus (GBS) meningitis. There was no statistical difference in linear growth between infants with aseptic and bacterial meningitis.ConclusionAcute bacterial meningitis in newborns and young infants is still associated with considerably high morbidity and complications. Infantile linear growth appears to be normal in all newborns and young infants with both bacterial and aseptic meningitis.

CLINICAL-EPIDEMIOLOGICAL CHARACTERISTICS OF ASEPTIC MENINGITIS IN CHILDREN OF KHMELNITSKYI REGION (PODILSKYI REGION, UKRAINE): FOURTEEN-YEAR EPIDEMIOLOGICAL OBSERVATION

Aim of work – to analyze the etiological structure, epidemiological structure, social-demographic features and the nature of the development of complications of the central nervous system in aseptic meningitis in children in Khmelnitskyi region for the period 2004-2017.Materials and methods. It was conducted a prospective analysis of 208 cases of aseptic meningitis in children of whom 138 people were boys and 70 people were girls. The etiology of the disease was determined by studying cerebrospinal fluid using PCR method. Complications of the central nervous system were diagnosed on the basis of the clinical picture and CT or MRI scans. The analytical method was used to conduct the analysis of the received data.Results. The highest seasonal increase of the incidence was from August to October and it was 65.6% with its peak in September (24.0%). The clinical picture was characterized by a moderate trend in 71.2% of cases and in 28.8% by a severe course. In 100% of cases the disease began with a fever, headache (83.6%), vomiting (76.9%), abdominal pain with diarrhea (6.2%), epileptic seizures (0.9%). The average level of cytosis was 269.4±196.7 cells/mm3with a predominance of lymphocytes and the average protein level in cerebrospinal fluid was 73 ± 36 mg/dl. The etiological factor was established in 18 (8.6%) patients.Conclusions. Enterovirus remains to be the main pathogen which was determined in 72.2% of cases. The second place was taken by herpes viruses (22.2% of cases), the third place was given to the mumps virus (5.6% of cases) (in etiologically verified cases). In most cases the disease ended in complete recovery but in 47 (22.6%) patients the complications were observed. The prevalence of aseptic meningitis among children in Khmelnitskyi region was 6.2 per 100,000 children, and males outnumbered females by a 2:1 ratio.

Clinical and laboratory characteristics of enteroviral meningitis in children, including qRT-PCR and sequencing analysis.

Enteroviruses (EVs) are the most common agents of aseptic meningitis. Some serotypes can cause serious neuroinfection leading to death. The aim of this study was to determine the representation of EVs in the etiology of aseptic meningitis in children and to analyze the demographic, clinical, laboratory, and epidemiological characteristics of patients with EV meningitis. This was a prospective study including 147 patients in three groups: EV meningitis, tick-borne encephalitis, and aseptic meningitis with unidentified agent. Boys with EV meningitis predominated over girls. The average patient age was 11 years. Compared to the control group, these patients suffered more from stiff back (P=0.010), vomiting and nausea (P=0.009). They had shorter symptom duration (P<0.001), higher C-reactive protein in blood (P<0.001), higher predominance of polynuclears (P=0.026), and greater lactate (P=0.003) in cerebrospinal fluid (CSF). The serotype seen most frequently (68%) was ECHO virus (ECV) 30. Enteroviruses play the most important role in the differential diagnosis of aseptic meningitis. Short symptom duration, slightly higher inflammatory parameters in blood, predominance of polynuclears, and elevated CSF lactate have predictive value in diagnosing this disease. ECV 30 (frequently the agent of epidemics in the Czech Republic) was the aseptic meningitis agent most often seen.

Sero-molecular epidemiology of enterovirus-associated encephalitis in Zhejiang Province, China, from 2014 to 2017

BackgroundRecently, both sporadic and outbreak aseptic meningitis caused by enteroviruses have been reported in Zhejiang Province based on a surveillance system. MethodsThis study analysed the epidemiologic features, phylogenetic characteristics and prevalence of enterovirus neutralizing antibodies (nAbs) from 2014 to 2017 in Zhejiang Province. ResultsA total of 584 samples were collected. Males accounted for 66.07% while females accounted for 33.93%. The median age was 6 years (range: 1–15 years). Cases peaked in May and August (81.17%) and 162 cases (28.93%) occurred in June. We detected 15 serotypes, some of which (E6, E9, E18 and E30) were the dominant serotypes prevalent in different years and geographical regions. Phylogenetic results revealed that all of the isolates from this study belonged to the human enterovirus B family. A total of 329 subjects sampled from a healthy population were tested for nAbs against B5, E6 and E30 in Rui’an county in 2015. The seropositive rate of E30 in each age group was significantly higher than that of the other serotypes. ConclusionEnterovirus-associated encephalitis pathogens circulating in Zhejiang caused sporadic aseptic meningitis in children. The level of nAbs against human enterovirus reflects the history of previous infections in different age groups. Therefore, additional surveillance sites and more precise seroprevalence studies based on these populations are required to gain better insight into the epidemiology of enterovirus-associated encephalitis in Zhejiang Province.

Risk Classification for Enteroviral Infection in Children With Meningitis and Negative Gram Stain.

Enterovirus is the most common cause of aseptic meningitis in children. This study aimed at identifying baseline variables associated with a positive cerebrospinal fluid (CSF) Enterovirus polymerase chain reaction (PCR) to aid clinicians in targeting patients who could be tested and treated as outpatients. We performed a retrospective review of children (2 months to 17 years old) admitted to the Children's Memorial Hermann Hospital in Houston, TX, between January 2005 and December 2010 with symptoms of meningitis, CSF white cell count of greater than 5 cells/mm, and a negative CSF Gram stain, who had a CSF Enterovirus PCR. One hundred thirty-seven children were reviewed; median age was 4.7 (0.1-17.1) years, and 79 (58%) were male. Fifty patients (37%) had positive CSF Enterovirus PCR. Only 13 (15%) of the Enterovirus PCR-negative patients had an identifiable etiology. All patients were hospitalized. The mean hospital stay for patients with Enterovirus was 2.9 days; 88% received empiric antibiotics. Rates of antibiotic administration were not different between PCR-positive and PCR-negative groups (P > 0.05). All patients with Enterovirus had a favorable clinical outcome.A predictive model was created using 3 baseline variables independently associated with a positive Enterovirus PCR (P < 0.05): May to November presentation, CSF protein of less than 100 mg/dL, and absence of focal neurologic signs. The model classified patients into 2 risk categories for a positive Enterovirus PCR (low risk, 0% [0/17 patients]; high risk, 42% [50/120 patients]; P < 0.001). Our predictive model can be used to identify children for whom Enterovirus PCR testing is warranted. Such testing could avoid unnecessary hospitalization and antibiotic administration.

Serum interleukin-6 levels as an indicator of aseptic meningitis among children with enterovirus 71-induced hand, foot and mouth disease

ABSTRACTObjectives: The enterovirus EV71 is a major pathogen of hand, foot, and mouth disease (HFMD) in children. Aseptic meningitis is the most common neurologic complication of EV71-induced HFMD. Lumbar puncture is a crucial procedure in the diagnosis of aseptic meningitis. It is often performed based on physicians’ clinical suspicion. A diagnostic method that can aid in deciding whether this procedure should be performed is necessary. Cytokines are speculated to be associated with neurologic complications. In this study, we aimed to find an indicator of the presence of aseptic meningitis in children with EV71-induced HFMD.Methods: This cross-sectional study included children with EV71-induced HFMD. The children underwent lumbar puncture due to suspected aseptic meningitis. They were categorized into an aseptic meningitis complicated group (n = 54) and uncomplicated group (n = 47) based on the results of cerebrospinal fluid examination. Healthy children were included as controls (n = 51). The sample serum levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, and IL-13 were detected using multiplexed fluorescent bead-based immunoassays.Results: The levels of all cytokines were significantly higher in children with EV71-induced HFMD complicated with aseptic meningitis than in children with uncomplicated EV71-induced HFMD and controls (p < 0.001). Binary logistic regression analysis demonstrated that IL-6 had the strongest association with aseptic meningitis of all cytokines examined. According to receiver operating characteristic analysis, the optimal cutoff value for IL-6 was 66 pg/mL with maximum sensitivity and specificity.Conclusions: The results of this study suggest the association between higher production of cytokine and aseptic meningitis among children with EV71-induced HFMD. IL-6 was also suggested as an indicator of aseptic meningitis. Rapid measurement of IL-6 could be useful in deciding whether physicians should perform lumbar puncture on children.

Seroepidemiological and phylogenetic characterization of neurotropic enteroviruses in Ireland, 2005-2014.

Enteroviruses (EVs) are associated with a broad spectrum of clinical presentation, including aseptic meningitis (AM), encephalitis, hand, foot and mouth disease, acute flaccid paralysis, and acute flaccid myelitis. Epidemics occur sporadically and are associated with increased cases of AM in children. The present study describes the seroepidemiological analysis of circulating EVs in Ireland from 2005 to 2014 and phylogenetic characterization of echovirus 30 (E-30), enterovirus A71 (EV-A71), and enterovirus D68 (EV-D68). EV VP1 genotyping was applied to viral isolates and clinical samples, including cerebrospinal fluid (CSF), and those isolates that remained untypeable by neutralising anti-sera. An increase in AM cases from 2010 to 2014 was associated with an E-30 genogroup variant VII and sequences clustered phylogenetically with those detected in AM outbreaks in France and Italy. EV-D68 viral RNA was not detected in CSF samples and no neurological involvement was reported. Three EV-A71 positive CSF samples were identified in patients presenting with AM. A phylogenetic analysis of respiratory-associated EV-D68 and EV-A71 cases in circulation was performed to determine baseline epidemiological data. EV-D68 segregated with clades B and B(1) and EV-A71 clustered as subgenogroup C2. The EV VP1 genotyping method was more sensitive than neutralising anti-sera methods by virus culture and importantly demonstrated concordance between EV genotypes in faecal and CSF samples which should facilitate EV screening by less invasive sampling approaches in AM presentations.

Study of CSF C-reactive protein in meningitis to differentiate bacterial meningitis from aseptic meningitis in children between 1 month and 12 years of age

Background: Meningitis is a serious illness of childhood. CSF Gram stain and culture is the gold standard for diagnosis which is a costly and time consuming. So, this study was conducted with the objective to measure the specificity, sensitivity, positive and negative predictive values and diagnostic accuracy of CSF-CRP in the diagnosis of bacterial meningitis.Methods: This prospective study was conducted in Department of Pediatrics, National Institute of Medical Sciences and Research, Jaipur. Children between 1 month to 12 years of age admitted with acute history of fever and seizure were included. CSF was sent for CRP estimation and other laboratory investigations. CSF CRP was determined qualitatively and value &gt;6mcg/ml was considered positive. Patients were divided into three groups based on clinical and CSF findings. Group 1 (Bacterial meningitis), Group 2 (Aseptic Meningitis) and Group 3 (No meningitis/Control Group). Statistical analysis was done using software SPSS version 23.Results: 120 patients were enrolled in our study. 65% of our cases were males. The mean age of our cases was 74.9±39.8 months. 48 cases had bacterial meningitis, 42 cases had Aseptic Meningitis and 30 cases had no meningitis. CSF-CRP was positive in 35 cases of Bacterial meningitis, 6 cases of aseptic meningitis and negative in all cases of control group. Hence the Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value and Diagnostic Accuracy of CSF-CRP for diagnosis of bacterial meningitis were 72.92%, 85.71%, 85.71%, 73.47% and 78.89% respectively. CSF-CRP cases of bacterial meningitis were also found to have a poor outcome.Conclusions:CSF-CRP can be used as an initial test for the diagnosis of Bacterial Meningitis till other confirmatory test reports are awaited.