Enterovirus In Cerebrospinal Fluid Research Articles

Characteristics of enterovirus infection associated neurologic disease associated in a pediatric population in Spain

IntroductionEnteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection. Methodsretrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease. ResultsOur findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset—especially if associated with skin rash—was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis. ConclusionsAwareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.

Characteristics of enterovirus infection associated neurologic disease in a pediatric population in Spain

IntroductionEnteroviruses are a type of RNA-strained virus with more than 100 different genotypes. Infection can be asymptomatic, and, if any, symptoms can range from mild to severe. Some patients can develop neurological involvement, such as aseptic meningitis, encephalitis, or even cardiorespiratory failure. However, in children, the risk factors for developing severe neurological involvement are not well understood. The aim of this retrospective study was to analyze some characteristics associated with severe neurological involvement in children hospitalized for neurological disease after enterovirus infection. Methodsretrospective observational study analyzing clinical, microbiological and radiological data of 174 children hospitalized from 2009 to 2019 in our hospital. Patients were classified according to the World Health Organization case definition for neurological complications in hand, foot and mouth disease. ResultsOur findings showed that, in children between 6 months old and 2 years of age, the appearance of neurological symptoms within the first 12h from infection onset—especially if associated with skin rash—was a significant risk factor for severe neurological involvement. Detection of enterovirus in cerebrospinal fluid was more likely in patients with aseptic meningitis. By contrast, other biological samples (e.g., feces or nasopharyngeal fluids) were necessary to detect enterovirus in patients with encephalitis. The genotype most commonly associated with the most severe neurological conditions was EV-A71. E-30 was mostly associated with aseptic meningitis. ConclusionsAwareness of the risk factors associated with worse neurological outcomes could help clinicians to better manage these patients to avoid unnecessary admissions and/or ancillary tests.

Outbreak of Enterovirus Infection with Neurological Presentations in a Pediatric Population in Northern Spain: A Clinical Observational Study.

The study aimed to describe the cases of neurological disease related to the outbreak of enterovirus (EV) in three regions in Northern Spain during 2016. Multicenter retrospective observational study. Clinical, radiological, and microbiological data were analyzed from patients younger than 15 years with confirmed EV-associated neurological disease admitted to 10 hospitals of Asturias, Cantabria, and Castile and Leon between January 1 and December 31, 2016. Fifty-five patients were included. Median age was 24 months (interquartile range = 18.5 months). Fifteen patients were classified as aseptic meningitis (27.3%). In total, 37 cases presented brainstem encephalitis (67.3%), 25 of them due to EV-A71 with excellent prognosis (84.6% asymptomatic 2 months following the onset). Three cases of acute flaccid myelitis (5.5%) by EV-D68 were reported and presented persistent paresis 2 months following the onset. Microbiological diagnosis by reverse transcriptase polymerase chain reaction was performed in all cases, finding EV in cerebrospinal fluid in meningitis, but not in brainstem encephalitis and acute flaccid myelitis, where EV was found in respiratory or rectal samples. Step therapy was administrated with intravenous immunoglobulin (IVIG; 32.7%), methylprednisolone (10%), and plasmapheresis (3.6%). Four patients received fluoxetine (7.3%). Twenty patients needed to be admitted to pediatric intensive care unit (36.4%). Clinical, microbiological, and radiological diagnosis is essential in outbreaks of EV neurological disease, taking into account that it can be difficult to identify EV-A71 and EV-D68 in CSF, requiring throat or rectal samples. There is not specific treatment to these conditions and the efficacy and understanding of the mechanism of action of immune-modulatory treatment (IVIG, corticosteroids, and plasmapheresis) is limited.

Prospective case‐control study of enterovirus detection differences in children’s cerebrospinal fluid between multiplex PCR and real‐time RT‐PCR assay

BackgroundViral encephalitis is common in childhood. It is an acute brain parenchymal inflammation caused by a variety of viral infection, and enterovirus accounts for the majority. Due to atypical clinical manifestations, pathogenic testing is important for assisting clinical diagnosis. The purpose of this study was to evaluate the performance of the multiplex PCR assay compared with quantitative real‐time PCR for enterovirus detection.MethodsA prospective case‐control study was performed involving 103 pediatric patients suspected for viral encephalitis and cerebrospinal fluid (CSF) samples were collected and tested for 9 pathogens using multiplex PCR assay during April to November in 2018. In parallel, an aliquot of samples was tested for enterovirus infection by real‐time PCR assay.ResultsThere were 85.4% children were confirmed as viral encephalitis on discharge, the remaining ones were diagnosed as other CNS diseases, such as epilepsy. The specificity of the two methods was the same as that of the clinical diagnosis, but the sensitivity and consistency with clinical diagnosis of multiplex PCR were both higher than the real‐time PCR. Besides of enterovirus, multiplex PCR could also detect coinfection of enterovirus with Epstein‐Barr virus and mumps virus.ConclusionResults of multiplex PCR method are more consistent with the clinical diagnosis and are superior to real‐time PCR for detecting enterovirus in CSF.

Impact of decreasing cerebrospinal fluid enterovirus PCR turnaround time on costs and management of children with suspected enterovirus meningitis.

To estimate the impact of implementing in-hospital enterovirus (EV) polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) with same-day turn-around-time (TAT) on length-of-stay (LOS), antibiotic use and on cost per patient with suspected EV meningitis, compared with testing at an outside reference laboratory. A model-based analysis using a retrospective cohort of all hospitalized children with CSF EV PCR testing done between November 2013 and 2017. The primary outcome measured was the potential date of discharge if the EV PCR result had been available on the same day. Patients with positive EV PCR were considered for potential earlier discharge once clinically stable with no reason for hospitalization other than intravenous antibiotics. Descriptive statistics and cost-sensitivity analyses were performed. CSF EV PCR testing was done on 153 patients, of which 44 (29%) had a positive result. Median test TAT was 5.3 days (IQR 3.9–7.6). Median hospital LOS was 5 days (IQR 3–12). Most (86%) patients received intravenous antibiotics with mean duration of 5.72 ± 6.51 days. No patients with positive EV PCR had a serious bacterial infection. We found that same-day test TAT would reduce LOS and duration of intravenous antibiotics by 0.50 days (95%CI 0.33–0.68) and 0.67 days (95%CI 0.42–0.91), respectively. Same-day test TAT was associated with a cost reduction of 342.83CAD (95%CI 178.14–517.00) per patient with suspected EV meningitis. Compared with sending specimens to a reference laboratory, performing CSF EV PCR in-hospital with same-day TAT was associated with decreased LOS, antibiotic therapy, and cost per patient.

Antibodies to Enteroviruses in Cerebrospinal Fluid of Patients with Acute Flaccid Myelitis.

Acute flaccid myelitis (AFM) has caused motor paralysis in >560 children in the United States since 2014. The temporal association of enterovirus (EV) outbreaks with increases in AFM cases and reports of fever, respiratory, or gastrointestinal illness prior to AFM in >90% of cases suggest a role for infectious agents. Cerebrospinal fluid (CSF) from 14 AFM and 5 non-AFM patients with central nervous system (CNS) diseases in 2018 were investigated by viral-capture high-throughput sequencing (VirCapSeq-VERT system). These CSF and serum samples, as well as multiple controls, were tested for antibodies to human EVs using peptide microarrays. EV RNA was confirmed in CSF from only 1 adult AFM case and 1 non-AFM case. In contrast, antibodies to EV peptides were present in CSF of 11 of 14 AFM patients (79%), significantly higher than controls, including non-AFM patients (1/5 [20%]), children with Kawasaki disease (0/10), and adults with non-AFM CNS diseases (2/11 [18%]) (P = 0.023, 0.0001, and 0.0028, respectively). Six of 14 CSF samples (43%) and 8 of 11 sera (73%) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas the three control groups were not immunoreactive in either CSF (0/5, 0/10, and 0/11; P = 0.008, 0.0003, and 0.035, respectively) or sera (0/2, 0/8, and 0/5; P = 0.139, 0.002, and 0.009, respectively).IMPORTANCE The presence in cerebrospinal fluid of antibodies to EV peptides at higher levels than non-AFM controls supports the plausibility of a link between EV infection and AFM that warrants further investigation and has the potential to lead to strategies for diagnosis and prevention of disease.

Meningitis por enterovirus: un reporte de casos en la región del Oriente de Antioquia, Colombia

Antecedentes: Los enterovirus son la principal causa de meningitis infecciosa en la edad pediátrica. Hacer la diferenciación por clínica y laboratorio entre las diversas etiologías infecciosas resulta impreciso.Resumen del caso: En este estudio realizamos la descripción de 13 pacientes pediátricos que ingresaron a nuestra institución con un cuadro clínico compatible con meningitis y en quienes se realizó detección de enterovirus en líquido cefalorraquídeo mediante técnicas moleculares.Conclusiones: A través de métodos como la detección de enterovirus en el líquido cefalorraquídeo, puede obtenerse el diagnóstico de meningitis viral de forma rápida, disminuyendo el uso de antibiótico y la estancia hospitalaria.

Internal verification of the cepheid Xpert enterovirus real-time PCR assay for the rapid detection of enterovirus in cerebrospinal fluid specimens

Aim: The Cepheid Xpert Enterovirus (EV) real-time PCR assay on Cepheid Xpert DX instrument was evaluated for use by the NSW Health Pathology Microbiology Department Wollongong for the rapid detection of EV in cerebrospinal fluid (CSF) specimens collected from patients presenting with suspected acute viral meningitis to Illawarra Shoalhaven Local Health District (ISLHD) facilities.

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.

Assessment of blood enterovirus PCR testing in paediatric populations with fever without source, sepsis-like disease, or suspected meningitis: a prospective, multicentre, observational cohort study

SummaryBackgroundEnteroviruses are the most frequent cause of acute meningitis and are seen increasingly in sepsis-like disease and fever without source in the paediatric population. Detection of enterovirus in cerebrospinal fluid (CSF) specimens by PCR is the gold standard diagnostic test. Our aim was to assess a method of detecting enterovirus in blood specimens by PCR.MethodsWe did a prospective, multicentre, observational study at 35 French paediatric and emergency departments in 16 hospitals. We recruited newborn babies (aged ≤28 days) and infants (aged >28 days to ≤2 years) with fever without source, sepsis-like disease, or suspected meningitis, and children (aged >2 years to ≤16 years) with suspected meningitis, who were admitted to a participating hospital. We used a standardised form to obtain demographic, clinical, and laboratory data, which were anonymised. Enterovirus PCR testing was done in blood and CSF specimens.FindingsBetween June 1, 2015, and Oct 31, 2015, and between June 1, 2016, and Oct 31, 2016, we enrolled 822 patients, of whom 672 had enterovirus PCR testing done in blood and CSF specimens. Enterovirus was detected in 317 (47%) patients in either blood or CSF, or both (71 newborn babies, 83 infants, and 163 children). Detection of enterovirus was more frequent in blood samples than in CSF specimens of newborn babies (70 [99%] of 71 vs 62 [87%] of 71; p=0·011) and infants (76 [92%] of 83 vs 62 [75%] of 83; p=0·008), and was less frequent in blood samples than in CSF specimens of children (90 [55%] of 163 vs 148 [91%] of 163; p<0·0001). Detection of enterovirus was more frequent in blood samples than in CSF specimens of infants aged 2 years or younger with fever without source (55 [100%] of 55 vs 41 [75%] of 55; p=0·0002) or with sepsis-like disease (16 [100%] of 16 vs nine [56%] of 16; p=0·008). Detection of enterovirus was less frequent in blood than in CSF of patients with suspected meningitis (165 [67%] of 246 vs 222 [90%] of 246; p<0·0001).InterpretationTesting for enterovirus in blood by PCR should be an integral part of clinical practice guidelines for infants aged 2 years or younger. This testing could decrease the length of hospital stay and reduce exposure to antibiotics for low-risk patients admitted to the emergency department with febrile illness.FundingUniversity Hospital Clermont-Ferrand.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger

To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4). Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

The spectrum of aseptic central nervous system infections in southern Germany - demographic, clinical and laboratory findings.

Aseptic infections of the central nervous system (CNS) are frequently observed in Germany. However, no study has systematically addressed the spectrum of aseptic CNS infections in Germany. Data on 191 adult patients diagnosed from January 2007 to December 2014 with aseptic meningitis or encephalitis/meningoencephalitis at our hospital were collected by chart review and analyzed for demographic, clinical and laboratory findings. Patients were stratified according to the causative virus and findings were compared between groups. In our cohort, meningitis was caused in 36% by enterovirus (EV), 15% by herpes simplex virus (HSV), 12% by varicella zoster virus (VZV) and 5% by tick borne encephalitis (TBE). Encephalitis/meningoencephalitis was caused in 13% by HSV, 13% by VZV, and three out of 11 tested patients were positive for TBE. The highest incidence of EV infections was between 25 and 35 years and of HSV infections between 30 and 60 years. VZV infections had a bimodal distribution peaking below 30 and above 70 years. VZV and EV infections were more frequently observed during summer, whereas HSV infections showed no seasonal preference. Inflammatory changes in cerebrospinal fluid (CSF) were highest in HSV and lowest in EV infections. Polymerase chain reaction tests for HSV, VZV and EV in CSF and TBE serology determined the causative virus in over 60% of tested patients. The age of affected patients, seasonal distribution, disease course and inflammatory changes in CSF differ between groups of patients affected by the most common viral infections.

Human enteroviruses in cerebrospinal fluid of children with suspected aseptic meningitis: A study in northern Iran.

Background:Enterovirus (EV) infections are one of the most common causes of aseptic meningitis in pediatrics. To diagnose EV meningitis, virus isolation in cell cultures is often time consuming and lacks sensitivity to be of clinical relevance. This makes the virus culture results difficult to interpret. The rapid detection of EVs in cerebrospinal fluid (CSF) by molecular diagnostic techniques may improve the management of patients with aseptic meningitis. The purpose of the present study was to develop a more convenient and sensitive alternative technique to viral culture. The current investigation aimed to explore the prevalence of EVs in CSF of children with suspected aseptic meningitis in northern Iran, between June 2014 and March 2015 via the one-step real-time RT-PCR technique.Methods:A single center cross-sectional study was carried out on 50 children suspected with aseptic meningitis, aged 6 months to 13 years. The presence of EV RNA in CSF samples was screened by the use of qualitative one-step real-time RT-PCR.Results:Enteroviral RNA was detected in 9 (18%) subjects using the one-step real-time RT-PCR assay. There was significant difference between EV positive and negative subjects regarding mean age (P=0.023), mean lymphocyte percentage (P=0.001) and mean glucose levels in CSF (P=0.037). The disease onset data indicate that the majority of EV meningitis occurred in the summer.Conclusion:This study provides the first data on the prevalence and epidemiology of EV infections in children with suspected aseptic meningitis in northern Iran.

Can We Distinguish between Human Parechovirus Type 3 and Enteroviruses Infection in Neonates and Young Infants Based on their Clinical and Laboratory Findings?

BackgroundHuman parechovirus type 3 (HPeV3) and enteroviruses (EVs) are the major viral pathogens causing severe diseases in neonates and young infants. Although two infections typically occur in summer, and initial clinical presentations are similar, differences in clinical and laboratory characteristics of HPeV3- and EV- infections are not well described.MethodsFrom January 2014 to December 2016, we prospectively obtained serum and/or cerebrospinal fluid (CSF) samples from febrile neonates and young infants < 4 months suspecting sepsis and meningoencephalitis in Niigata, Japan. RNA/DNA were extracted from the samples and viral etiologies including HPeV3, EVs, and/or herpes simplex virus were tested using the real-time PCR, followed by genetic sequencing and typing. The comparison was made between HPeV3- and EVs-infected patients based on their medical records and subsequent questionnaires using appropriate statistical analyses.ResultsIn total, we obtained 212 serum and 170 CSF samples from 222 patients. HPeV3 and EVs were detected for 56 (25%) and 43 patients (19%) (Figure), and their median ages were 29 and 24 days (P = 0.58), respectively. HPeV3-infected patients presented with higher median body temperature (38.9 °C vs 38.5 °C, P < 0.001), heart rates (184/minute vs. 161/minute, P = 0.002), peripheral coldness (72% vs. 34%, P < 0.001), skin mottling (65% vs. 23%, P < 0.001), and grunting (22% vs. 5%, P = 0.014) than EVs-infected patients. Additionally, systemic inflammatory response syndrome (SIRS) was more frequently observed in HPeV3-infected patients than in EVs-infected patients (82% vs. 58%, P = 0.009). In the laboratory data, median white blood cell count was lower in HPeV3-infected patients than those in EVs-infected patients (5,200/µL vs. 8,900/µL, P < 0.001). The pleocytosis was observed 58% of EVs-infected patients, but none of the HPeV3-infected patients (P < 0.001); however, HPeV3 RNA was frequently detected than EVs in CSF (90% vs 66%, P = 0.012).ConclusionThis study showed that HPeV3-infected neonates and young infants presented more severe clinical manifestations than those infected with EVs. Significant tachycardia, poor peripheral circulation, and fulfilling SIRS criteria at the presentation may be the clues considering HPeV3 infection rather than EVs infection.Disclosures All authors: No reported disclosures.

Clinical utility of stool polymerase chain reaction in pediatric patients with suspected enteroviral meningitis

The purpose of this study was to evaluate whether stool polymerase chain reaction (PCR) has a higher clinical sensitivity for detecting enterovirus compared with cerebrospinal fluid (CSF) PCR in pediatric patients suspected to have enteroviral meningitis. We retrospectively reviewed 139 pediatric patients with enteroviral meningitis diagnosed in our hospital during 2010–2012. Enteroviral meningitis was diagnosed based on detection of virus in CSF and/or stool samples in aseptic meningitis patients. Patients were divided into definitive enteroviral meningitis (positive CSF PCR) and highly probable enteroviral meningitis (negative CSF PCR, but positive stool PCR) groups. The clinical characteristics of the two groups were compared to identify the characteristics of patients with highly probable enteroviral meningitis. We also analyzed the influence of sampling time on the PCR results of the two specimen types. Patients with highly probable enteroviral meningitis had a lower white blood cell count in CSF ( P P = 0.03) than did patients with definitive enteroviral meningitis. The CSF enterovirus positivity rate was lower in CSF specimens obtained > 1 day after clinical onset, whereas the majority of stool samples were PCR positive throughout the course of the disease. Our results suggest that PCR of stool specimens may be useful in pediatric patients with suspected enteroviral meningitis, particularly when the duration of symptoms is >1 day and/or a lower degree of CSF pleocytosis is observed.

Epidemic Trends of Enterovirus Infections From Pediatric Patients in Cheonan, Korea.

This study was performed to investigate the epidemiology of enterovirus (EV) infections in children at a single hospital during recent 5 years. This study was preformed from December 2008 to November 2013. We subjected 1,067 cerebrospinal fluid (CSF) specimens from 1,053 patients and 678 stool specimens from 665 patients using real-time reverse-transcription polymerase chain reaction tests that could detect EV. The data were analyzed according to seasonality and patient age and sex. During this period, 176 of the total 1,053 patients (16.81%) were positive for EV in CSF. The highest rate of EV-positive samples occurred in children less than 1 year of age (114/176, 64.77%), and the most prevalent month was June. The results for CSF and stool specimens were concordant in 545 (80.38%) of 678 cases. We described the epidemiological analytic data of the EV in the population of Cheonan, South Korea. The combination of the CSF and stool specimen enhances the diagnostic yield. There is a need for continuous study of EV infections and its clinical manifestations.

Rapid detection of enterovirus in cerebrospinal fluid by a fully-automated PCR assay is associated with improved management of aseptic meningitis in adult patients

BackgroundEnterovirus (EV) is the most frequent cause of aseptic meningitis (AM). Lack of microbiological documentation results in unnecessary antimicrobial therapy and hospitalization. ObjectivesTo assess the impact of rapid EV detection in cerebrospinal fluid (CSF) by a fully-automated PCR (GeneXpert EV assay, GXEA) on the management of AM. Study designObservational study in adult patients with AM. Three groups were analyzed according to EV documentation in CSF: group A=no PCR or negative PCR (n=17), group B=positive real-time PCR (n=20), and group C=positive GXEA (n=22). Clinical, laboratory and health-care costs data were compared. ResultsClinical characteristics were similar in the 3 groups. Median turn-around time of EV PCR decreased from 60h (IQR (interquartile range) 44–87) in group B to 5h (IQR 4–11) in group C (p<0.0001). Median duration of antibiotics was 1 (IQR 0–6), 1 (0–1.9), and 0.5 days (single dose) in groups A, B, and C, respectively (p<0.001). Median length of hospitalization was 4 days (2.5–7.5), 2 (1–3.7), and 0.5 (0.3–0.7), respectively (p<0.001). Median hospitalization costs were $5458 (2676–6274) in group A, $2796 (2062–5726) in group B, and $921 (765–1230) in group C (p<0.0001). ConclusionsRapid EV detection in CSF by a fully-automated PCR improves management of AM by significantly reducing antibiotic use, hospitalization length and costs.

PO-0256 Enterovirus Meningitis: A Case Series Review

<h3>Background and aims</h3> Meningitis due to Enterovirus infection is usually mild and self-limiting, particularly affecting young infants. We found that we were increasingly diagnosing the condition and undertook a retrospective review, exploring case characteristics and whether increasing use of virology detection reduced antibiotic course length, having previously rarely employed these techniques. <h3>Methods</h3> All cases identified as being diagnosed with meningitis with a positive enterovirus polymerase chain reaction (PCR) result between January 2012 and December 2012, below 16 years of age, were retrospectively reviewed. <h3>Results</h3> Nine cases of enterovirus meningitis were identified in the time period. Seven were infants aged 3 months or less, with two patients aged 11 and 15 years respectively. There were five females and four males. The infants presented with fever, lethargy or irritability. The older children presented with fever and headache. Following full infection screens, all of the infants were treated with intravenous antibiotics. One patient had raised inflammatory markers and one patient had a significant cerebrospinal fluid (CSF) pleocytosis, the majority had a normal or minimally raised CSF white cell count. Eight patients had positive CSF Enterovirus PCR results and one patient had a Coxsackievirus positive serum PCR (having not undergone lumbar puncture). In three patients a prolonged course of antibiotics was discontinued following the PCR result. One patient had episodes of tachycardia with subsequent diagnosis of supraventricular tachycardia requiring treatment. <h3>Conclusion</h3> Positive enterovirus PCR results appear to have reduced antibiotic course length, limiting unnecessary antibiotic administration, and we advocate increasing use of this investigation.

Distinct systemic and central nervous system disease patterns in enterovirus and parechovirus infected children

Enteroviruses (EV) and human parechoviruses (HPeV) infections are increasingly identified in neonates and young children with sepsis, meningitis and encephalitis. We investigated EV and HPeV viral loads in plasma and cerebrospinal fluid (CSF) among those presenting with sepsis or central nervous system (CNS) disease to gain understanding of the nature of these infections. Detections frequencies and viral loads of EV and HPeV RNA were compared in plasma and CSF obtained from infected children originally identified on sepsis or CNS screening. Two distinct infection profiles were identified; 11 subjects with CNS disease, showed higher or similar viral loads in CSF than in plasma (median plasma:CSF ratio 0.5), whereas 14 children with sepsis showed low or undetectable viral loads in CSF and high viral loads in plasma (mean ratio 5700). HPeV type 3 and one EV serotype (coxsackievirus B2) were primarily associated with the latter presentation. Simple detection of EV or HPeV RNA in CSF is not predictive of CNS disease, especially in the absence of clinical markers (i.e. pleocytosis). Screening of plasma can identify EV and HPeV RNA in a substantial proportion of sepsis cases, some of which will be missed if CSF samples alone are screened.

Detection and genotyping of enteroviruses in cerebrospinal fluid in patients in Victoria, Australia, 2007-2013

Genotyping by VP1 fragment polymerase chain reaction (PCR) and nucleic acid sequencing to detect enterovirus (EV) genotypes was performed directly on 729 EV PCR positive cerebrospinal fluid (CSF) samples collected between 2007 and 2012 from Victorian hospital inpatients. The overall genotype identification rate from CSF-positive material was 43%. The four most common genotypes identified were Echovirus 6 (24%), Echovirus 30 (17%), Echovirus 25 (10%), and Coxsackievirus A9 (10%), together comprising 61% of all EVs typed. The seasonal distribution of all EVs identified followed the recognized pattern of mainly summer epidemics. Three of the four predominant genotypes were present in each of the 6 years in which the study was conducted, with 20 other EV genotypes also detected, often in only a single year. Genotyping of EVs directly in CSF is faster, simpler and more sensitive than traditional virus neutralization assays performed on EV positive samples.