BACKGROUND:Human Parechovirus (HPeV) and Enterovirus (EV) are known causes of viral infection and meningitis in childhood. Not much is known about the motor development of young Caucasian children after these infections. Most studies in the literature involved Asian children with only EV-71 infection, which is not prevalent in Western countries.METHODS:In this prospective multicenter blinded cohort study we tested the motor function level of children 24 months after an HPeV or EV infection (meningitis or elsewhere) and uninfected peers, with Bayley Scales of Infant Development -3 (BSID-3) and Movement Assessment Battery for Children-2 (M-ABC-2-NL). The total motor outcome, the fine motor function outcome and the gross motor function outcome were measured. Impaired motor development was defined as a z-score ≤-1.RESULTS:Of the 157 analyzed children, the total motor outcome was impaired in 16 (10%), the gross motor function was impaired in 26 (27%) and the fine motor function in 9 (6%) children. There was no significant difference between the outcome of children with a meningitis, an infection elsewhere and uninfected peers. In addition, no differences in motor development were found in a subgroup analysis after correcting for confounders, including age and gender.CONCLUSIONS:No significant differences in motor development were found between HPeV or EV infected and uninfected Dutch children after 24 months of follow-up.

This multicenter prospective cohort study describes the impact of human parechovirus meningitis on gross-motor neurodevelopment of young children. Gross-motor function was measured using Alberta Infant Motor Scale. Of a total of 38 eligible children < 10 months of age at onset, nine cases had clinical evidence of meningitis and polymerase chain reaction positive for human parechovirus in cerebrospinal fluid; 11 had no meningitis and polymerase chain reaction positive for human parechovirus in nasopharyngeal aspirate, blood, urine, or feces; and in 18, no pathogen was identified (reference group).

Enterovirus (EV) and Parechovirus (HPeV) are a frequent cause of infection in children. This review gives an overview of possible causes for differences in clinical presentation. EV and HPeV can cause a meningitis with or without pleocytosis. Different possible mechanisms for meningitis without pleocytosis are given. Little is known about the prognosis and long-term effects of EV and HPeV meningitis in children. Only some studies with a small number of children with EV or HPeV meningitis are reported. The different possible mechanisms involved in the neurological outcome after EV or HPeV meningitis will be discussed.

BACKGROUND:Human non-polio enterovirus (EV) and human parechovirus (HPeV) are important pathogens of viral infection and aseptic meningitis in children. The aim of this study is to prospectively compare the incidence, clinical signs, blood and cerebrospinal fluid in EV and HPeV infected children. OBJECTIVES:To compare the clinical symptoms and laboratory data of children with different EV and HPeV genotypes. STUDY DESIGN:This study is part of a multicenter prospective cohort study. Children were included in 3 different hospitals in The Netherlands from 2008 to 2011. RESULTS:Of 285 included patients, 140 (49%) had EV and 44 (15%) HPeV infection. Of children with EV infection 9 (6%) had EV-A, 109 (78%) EV-B, 12 (9%) had a non-type able EV and in 10 (7%) no genotyping was performed. Of children with HPeV infection, 24 (55%) had HPeV-3, 6 (14%) HPeV-1, 2 (5%) HPeV-4 and 1 (2%) HPeV-6. Meningitis was more frequent in EV than in HPeV infected children (54% vs. 36%, p=0.046), and in EV-B than EV-A infected children (60 vs. 33%). In contrast gastroenteritis was more frequent in HPeV than EV infected children (30% vs. 15%, p=0.030), and significantly more in HPeV-1 than HPeV-3 infected children (p<0.001). CONCLUSIONS:EV infection is more often associated with meningitis and HPeV infection more often with a gastro-enteritis. EV genotype B infection is more often associated with meningitis than EV genotype A infection. HPeV-1 infection was more often associated with gastroenteritis than HPeV-3 infection.

Enterovirus and parechovirus are a frequent cause of infection in children. This review is an overview of what is known from enterovirus and parechovirus infection in children and contains information about the epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and prognosis of enterovirus and parechovirus infection in children. Conclusions: EV and HPeV infections are a frequent cause of infection in childhood. The clinical presentation is diverse. RT-qPCR is the best way to detect an EV or HPeV. Cerebrospinal fluid, blood and feces have the highest sensitivity for detecting an EV or HPeV. There is no treatment for EV and HPeV infections. Two vaccines against EV 71 are just licensed in China and will be available on the private market. Little is known about the prognosis of EV and HPeV infections.

Both human Enterovirus (EV) and Parechovirus (HPeV) central nervous system (CNS) infection have been reported to cause neuronal damage in several brain areas. This may result in cognitive and behavioural problems, especially in young children with developing brains. There are scanty studies with conflicting results available. This study aimed to determine the impact of EV and HPeV infection on the cognitive and behavioural development of Dutch children aged between 0 and 5 years. We compared the cognitive and behavioural developments of children with EV and HPeV meningitis (case-group) with those of two control groups; those with EV/HPeV elsewhere and those without EV or HPeV infection (healthy peers). Multivariate analyses showed that the cognitive and behavioural development of children with EV and HPeV meningitis did not differ significantly from those of children from the two control groups. However, it showed that a lower verbal intelligence quotient (VIQ) was associated with older age at assessment (β=-0.29) and longer duration of time since diagnosis until psychological testing (β=-0.22). An older age at infection was more associated with internalizing and externalizing problems (respectively, β=0.37 and β=0.34) than a younger age. Children with an EV infection were more prone to externalizing problems (β=-0.32) than those with HPeV. In conclusion, we did not find any difference in cognitive development of children with EV or HPeV meningitis. However, older age was associated with lower VIQ and behavioral problems, especially in children with EV infection.

Background: Reverse-transcriptase quantitative real-time polymerase chain reaction (RT-qPCR) has become the gold standard for the diagnosis of human enterovirus (EV) and parechovirus (HPeV) infections. The detection rate of RT-qPCR in different pediatric body specimens has not been compared prospectively in a multicentre study.Objectives: This study compared the diagnostic detection rates of EV and HPeV RT-qPCR and viral culture in different specimens (feces, nasopharynx, blood, urine and cerebrospinal fluid (CSF)) of pediatric patients.Study design: This prospective, multicenter study performed an EV and HPeV RT-qPCR on nasopharynx, blood, urine, feces and CSF specimens and a viral culture on nasopharynx, feces and CSF specimens in symptomatic children < 16 years.Results: Of 285 included children EV was detected in 140 (49%) and HPeV in 44 (15%) children. Both EV and HPeV RT-qPCR had a higher sensitivity and negative predictive value than EV and HPeV viral culture, respectively. EV and HPeV RT-qPCR in feces specimen had the highest sensitivity (99.2% and 95.1%) of all specimens. Pooling results of specimens increased the detection rate for both viruses.Conclusion: Of all specimens, RT-qPCR in feces had the highest detection rate for both EV and HPeV in symptomatic pediatric patients. An EV was detected in all EV positive patients if a RT-qPCR was performed on both feces and CSF specimens or in both feces and urine specimens. HPeV was detected in all HPeV positive patients if a RT-qPCR was performed on both feces and CSF specimens, feces and nasopharynx specimens or CSF and nasopharynx specimens. (C) 2013 Elsevier BAT. All rights reserved.

Human non-polio enterovirus (EV) is the most important cause of aseptic meningitis in children. Only a few studies report the lack of cerobrospinal fluid (CSF) pleocytosis in children with confirmed EV meningitis; however, the characteristics of these children have not been well defined. This paper describes the clinical and laboratory features of EV meningitis in children with no CSF pleocytosis. Clinical, laboratory, and virological data of Dutch patients <16 years diagnosed with EV meningitis, between 2003 and 2008, were analyzed retrospectively. Data of children with and without CSF pleocytosis were compared. A total of 149 children were infected with EV. Patients presented mainly with fever (n = 113), malaise (n = 43), abdominal pain (n = 47), and irritability (n = 61). Of the 60 patients with EV meningitis, 23 had no pleocytosis. Those who lacked CSF pleocytosis were younger [odds ratio (OR) 1.00; 95% confidence interval (CI) 1.000–1.002; p = 0.001], had experienced drowsiness more (OR 9.60; 95% CI 2.24–41.15; p = 0.002), had lower white blood cell counts (OR 0.73; 95% CI 0.61–0.89; p = 0.001), and had higher C-reactive protein (OR 1.13; 95% CI 1.03–1.23; p = 0.006) than those with pleocytosis. Conclusion. These findings show that EV meningitis occurs in the absence of CSF pleocytosis, particularly in young infants, meaning that EV meningitis in this age group cannot be solely excluded by the absence of CSF pleocytosis. They also confirm the importance of genome detection in the diagnosis of EV meningitis in young infants.

Enterovirus (EV) and human parechovirus (HPeV) are a major cause of infection in childhood. A rapid diagnostic test may improve the management of patients with EV and HPeV infection. The aim of this study is to evaluate the performance of the GeneXpert enterovirus assay (GXEA) for detection of EV RNA compared to a user-developed reverse-transcriptase (RT) quantitative real-time PCR (qPCR) in routine clinical practice. Also a RT-qPCR assay for detection of HPeV RNA in different clinical samples was developed and evaluated. Cerebrospinal fluid (CSF) from 232 patients suspected for meningitis was collected and tested for EV and HPeV using RT-qPCR assays. In parallel an aliquot of the samples was tested using the GXEA and viral culture. EV RNA was detected in 22 (19.0%) and 28 (24.1%) of 116 samples using the GXEA and RT-qPCR assay, respectively. EV was isolated from 10 of 116 (8.6%) samples by viral culture. GXEA had a sensitivity, specificity, positive predictive value and negative predictive value of 82.1%, 100%, 100% and 96.2%, respectively. In this study, molecular assays were superior to viral culture for detecting EV RNA in CSF. GXEA showed a high specificity but a lower sensitivity for the detection of EV RNA compared to the RT-qPCR assay.