• Clinical and Experimental Pediatrics
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• v.58 no.11
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• pp.446-450
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• 2015

Purpose: Meningitis is among the most common infections affecting the central nervous system. It can be difficult to determine the exact pathogen responsible for the infection and patients are often treated with empiric antibiotics. This study was conducted to identify the most common clinical characteristics of enteroviral meningitis in children and evaluate the diagnostic efficacy of reverse transcriptase-polymerase chain reaction (RT-PCR) for early detection of an enterovirus. Methods: We analyzed the medical records of children admitted to Korea University Medical Center and diagnosed with meningitis on the basis of cerebrospinal fluid (CSF) analysis and RT-PCR from CSF and other samples from January 2010 to August 2013. Results: A total of 333 patients were enrolled and classified into four groups based on diagnosis: enteroviral meningitis (n=110), bacterial meningitis (n=23), other viral meningitis (n=36), and unknown etiology (n=164). Patients with bacterial meningitis were younger than those in the other groups (P<0.001). Pleocytosis in CSF was similar across all groups. Of patients in the enteroviral meningitis group, 92.7% were diagnosed based on RT-PCR findings. Mean length of hospital stay for patients with enteroviral meningitis was 6.08 days, which was significantly shorter than that for patients with meningitis of bacterial etiology (19.73 days, P<0.001). Conclusion: Diagnosis of enteroviral meningitis before viral culture results are available is possible using RT-PCR. Accurate diagnosis reduces the length of hospital stay and helps to avoid unnecessary empiric antibiotic treatment.

• Pediatric Infection and Vaccine
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• v.3 no.2
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• pp.163-167
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• 1996

Aseptic meningitis, the most common infection of the central nervous system, is an acute illness mostly caused by enteroviruses. Cerebrospinal fluid(CSF) has been used for the detection of enteroviral RNA but the detection has been mostly performed in a single CSF specimen obtained during the illness. A major objective was to evaluate the relation of sampling time to the recovery of enteroviral RNA in CSF. Thirty seven CSF specimens were obtained from 24 patients between May and August 1993, when an outbreak of asceptic meningitis by echovirus type 9 occurred. Enteroviral RNA in CSF was detected by polymerase chain reaction(PCR). Data about onset of symptom development were obtained by review of medical records. Enteroviral RNA was detected by PCR in 29 of 37 CSF specimens. PCR yielded positive results in 4 of 5 CSF specimens obtained on day 1 to 3, 10 of 11 on day 4 to 6, 8 of 10 on day 7 to 9, 6 of 8 on day 10 to 12, 1 of 3 on day 13 to 15 postonset. Of 11 patients from each of whom more than one CSF were obtained on different day postonset, PCR yielded positive resutls in 2 of 3 cases in whom enteroviral RNA detection was negative in the first CSF. These results indicate that two or more CSF specimens obtained within 12 days postonset are required for improving the accuracy of the diagnosis of enteroviral meningitis.

• Journal of the Korean Child Neurology Society
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• v.26 no.4
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• pp.246-250
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• 2018

Purpose: Meningitis is an acute childhood infection caused by viral or bacterial infection. The purpose of the present study is to analyze the differences between enteroviral meningitis and non-enteroviral aseptic meningitis. Methods: From January 2013 to December 2016, we retrospectively reviewed the medical records of a total of 303 aseptic meningitis patients who visited Wonju Severance Christian Hospital. We examined demographics of all patients and analyzed serologic and cerebrospinal fluid tests, clinical symptoms, and outcomes. Results: Of a total of 303 patients, 197(65.0%) were male, and the most cases occurred from June to November (91.8%). The most common pathogen of meningitis was found to be enterovirus (65.0%). According to the etiology, the enteroviral meningitis group had significantly more headache and enteric symptoms (P=0.0003 and P=0.0013, respectively). Furthermore, the non-enteroviral meningitis group showed pleocytosis in the cerebrospinal fluid and a significantly higher rate of seizure at 1 to 4 years (P=0.0360 and P=0.0002, respectively). Conclusion: In this study, enteroviral meningitis was the most common and the prognosis was good. When compared between two groups, neurological symptoms were frequent in patients with non-enteroviral meningitis in groups 1 to 4 years.

• Pediatric Infection and Vaccine
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• v.6 no.2
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• pp.210-218
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• 1999

Purpose : As several epidemics of aseptic meningitis had been reported in Korea since 1990, the need of epidemiologic study about enteroviral infections was recognized. We studied epidemiologic and clinical features of enteroviral infections in children. Methods : We analyzed the seasonal occurrence of enteroviral infections and age, sex and clinical diagnosis of the children admitted to five branch hospitals of Hallym University and diagnosed to have enteroviral infections by culture from January 1996 to December 1998. Results : Enterovirus was isolated in 126 out of 245(51.4%) stools, 15 out of 89(16.8%) nasopharyngeal aspirates and 195 out of 1,835(10.6%) cerebrospinal fluids. There were 273 echoviruses(Echo)(197 Echo 30, 46 Echo 9, 17 Echo 6, 13 unclassified), 24 coxsackieviruses B(CB)(11 CB 2, 2 CB 5, 11 unclassified), 7 coxsackieviruses A 24 and 32 unclassified enteroviruses. Yearly number of isolates was 65(46 Echo 9) in 1996, 239(197 Echo 30) in 1997 and 32(15 CB: 9 CB 2) in 1998. Epidemics of enteroviruses occurred mainly during the months May to October. The mean age of the infected children was $62.1{\pm}38.0$ months and 74.6% of the patients were younger than 7 years of age. There were 203 boys and 100 girls and 79.3% of the patients were diagnosed as aseptic meningitis. Conclusions : We confirmed that enteroviral infections occurred in epidemics from late spring to fall during the study period. Enteroviral infections occurred predominantly in boys and the preschool children. Aseptic meningitis was the main illness in the hospitalized children.

• Clinical and Experimental Pediatrics
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• v.49 no.7
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• pp.745-750
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• 2006

Purpose : Enteroviruses are the most common cause of aseptic meningitis in patients of all ages. A definite diagnosis of enteroviral meningitis can be established by detection of virus directly in CSF specimens. But this is time-consuming and lacks sensitivity, so polymerase chain reaction(PCR) detecting of viral RNA in patient specimens such as CSF, stool has been demonstrated. But little is known about the influence of sampling time on the results of CSF PCR and stool PCR. We investigated diagnostic utility of PCR of CSF and stool according to sampling time after the onset of symptoms. Methods : PCR results were analyzed according to sampling time for 42 patients diagnosed aseptic meningits in our hospital from $11^{th}$ January to $30^{th}$ August, 2005. Results : The diagnostic yield of the test was higher of CSF specimens obtained ${\leq_-}2$ days after clinical onset(positive PCR results 9/18, 50 percent), compared with CSF collected >2 days after onset(positive PCR results 1/24, 4.2 percent)(P=0.001). Instead, positive PCR results of fecal specimens maintained highly(average 90.5 percent), 10 cases had also positive PCR results even 5-6 days after onset. 10 cases of CSF specimens had positive enterovirus PCR results containing coxsackievirus B5 (n=6), coxsackievirus B3(n=3). 38 cases of stool specimens had positive enterovirus PCR results containing echovirus 18(n=7), echovirus 9(n=3), coxsackievirus B5(n=8), coxsackievirus B3(n=3). 6 cases(coxackie B5) had positive CSF PCR and stool PCR, both. Conclusion : Stool PCR was clinically sensitive for detecting enterovirus during enteroviral meningits and could give a presumptive diagnosis throughout the disease course. A definite diagnosis was obtained by CSF PCR, but its utility was clearly lower for samples obtained >2 days after clinical onset. Therefore, it is recommended that, in addition to performance of CSF PCR, fecal samples obtained from patients with suspected enteroviral meningitis should be tested by PCR, especially when the duration of symptoms is >2 days.

• Pediatric Infection and Vaccine
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• v.17 no.2
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• pp.122-129
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• 2010

Purpose : Enteroviral infection is a common viral illness in children. We undertook this study in attempt to comprehend the epidemiologic and clinical features of enteroviral infections, particularly EV71 in children. Methods : We enrolled 63 children with enteroviral infection at Severance Children's Hospital in Seoul between May and August 2009. Reverse transcriptase-polymerase chain reaction (RT-PCR) was performed from stool or cerebrospinal fluid samples, which were then tested for enteroviral infection. Viral isolation and serotype identification also were performed by RT-PCR. Results : A total of 63 patients with clinical diagnosis of enteroviral infections were enrolled; of those, 38 (60%) were positive for enterovirus. The mean age of the patients was 2 years and 7 months and the sex ratio of male to female was 0.9 :1. Their clincal manifestations included aseptic meningitis (21 cases, 55%), HFMD (16 cases, 42%), herpangina (5 cases, 13%), neonatal fever (2 cases, 5%), encephalitis (1 case, 3%), and myocarditis (1 case, 3%). Serotypes of isolated enteroviruses were EV71 (8 cases, 21%), coxsackievirus B1 (8 cases, 21%), coxsackievirus A16 (2 cases, 6%), coxsakievirus A2 (1 case, 3%), coxsakievirus A5 (1 case, 3%), and echovirus 9 (1 case, 3%). Clinical symptoms of EV71 infection included HFMD (5 cases, 63%), aseptic meningitis (3 cases, 38%), encephalitis (1 case, 13%), and myocarditis (1 case, 13%). A positive rate of C-reactive protein in EV71 was higher than those in other enterviral infections. However, there was no statistically significant difference in other laboratory findings. Conclusion : We reported on identified enteroviruses, including EV71, during a period of 3 months in the summer of 2009. In this study, EV71 infection frequently occurred in male and clinical manifestation caused by EV71 was a more severe disease than that due to other enterviral infections. There is a need for continuous surveillance of enteroviral infection and its clinical manifestations for diagnosis and treatment of enteroviral infection.

• Clinical and Experimental Pediatrics
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• v.52 no.11
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• pp.1234-1240
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• 2009

Purpose:Enteroviruses (EVs) are commonly known to cause infection, especially in infants and children. This report presents an overview of enterovirus epidemiology in central Korea. Methods:From the spring of 2005 to the autumn of 2006, we collected the cerebrospinal fluid (CSF) and stool samples from the pediatric patients with a febrile illness or suspected meningitis who were admitted to hospitals in central Korea. In order to test for EVs, cell lines were derived from pretreated susceptible specimen, and the cytopathic effects were observed. Seminested real time-polymerase chain reaction (RT-PCR) and direct sequencing were performed for genotypic and phylogenetic analyses. Results:Of the 305 patients examined, 51 (16.7%) tested positive for EV. Of these 51 patients, 44 showed the following serotypes: Echovirus (ECV) 18 (18 cases, 35.2%), Coxsackievirus B (CVB) 5 (13 cases, 25.4%), ECV25 (5 cases, 9.8%), ECV9 (4 cases, 7.8%), ECV5 (3 cases, 5.8%), and EV74 (1 case, 1.9%). In 2005, between June and August, ECV18 and CVB5 were mostly responsible for the enteroviral infections among the patients in central Korea. In 2006, between July and August, ECV25 was mostly the cause of enteroviral infection. Conclusions:There is a need for continuous surveillance of enteroviral infection and its clinical manifestations, particularly for EV74, which was first identified in Korea.

• The Journal of Korean Society of Virology
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• v.26 no.2
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• pp.215-225
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• 1996

Aseptic meningits, an acute inflammation of the meninges, is a common illness during childhood. Virus is the most important cause of aseptic meningitis. Especially enterovirus causes approximately above 85% of all cases of aseptic meningitis. In 1993, there was a big epidemic of aseptic meningitis by ECHO 9 and ECHO 30 viruses. And ECHO 3 virus was isolated as a causative agent of aseptic meningitis in 1994. This study was aimed to detect the causative agent of aseptic meningitis in 1995 and to analyze the 5'-noncoding region which was used to detect virus. Virus was isolated from 87 stools and cerebrospinal fluid specimens of the patients by cultured RD and HEp-2 cell. Neutralizing antibody tests using enterovirus serum pool were performed on the specimens with cytopathic effect. 3 of ECHO 7 viruses and 5 of Coxsackie B3 viruses were isolated from stool specimens and 1 of ECHO 7 and Coxsackie B3 mixed type was confirmed from cerebrospinal fluid specimens. RNA was isolated from the culture supernatants of infected cells and general primers were selected in highly conserved part of the 5'-noncoding region of the enteroviral genome for RT-PCR. PCR product from this virus showed a 152bp band on gel electrophoresis. Sequence of obtained DNA was compared with prototype sequences by accessing to the Genebank database. 5'-noncoding region of isolated Coxsackie B3 virus, which has point mutations in nucleotide sequence positions 493, 497, 502, 523, was closely related to that of polio virus type 1, Mahoney strain. In case of isolated ECHO 7 virus, nucleotide has been changed from cytosine to thymine at position 581 and from thymine to cytosine at position 583. We concluded the causative agents of the outbreak of aseptic meningitis during June to July in 1995 were both ECHO 7 and Coxsackie B3 virus, and the primer used in this study could allow a rapid diagnosis of enteroviruses by PCR.

• Pediatric Infection and Vaccine
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• v.16 no.1
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• pp.73-79
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• 2009

Purpose : We undertook this study to improve our understanding of the epidemiologic and clinical features of nonpolioenterovirus (NPEV) infections, especially enterovirus 71 (EV71) infections, in Korean children. Methods : Between April and June 2000, NPEVs were detected by RT-PCR and cultures of specimens obtained from patients with aseptic meningitis, acute respiratory disease, and acute gastroenteritis which were associated with enteroviral exanthem and vesicular pharyngeal enanthem, such as herpangina, and hand, foot, and mouth disease (HFMD). EV71 was identified by sequencing the VP1 gene. The clinical and epidemiologic data were analyzed retrospectively after all 87 NPEV-positive patients were divided into 4 groups, according to the clinical manifestations. Sixteen patients who mainly had symptoms of acute gastroenteritis were in group A, 21 patients with symptoms and signs of lower respiratory tract infections were in group B, 42 patients with a HFMD rash only were in group C with or without fever, and 8 patients with aseptic meningitis or paralysis were in group D. For the 11 EV71-positive patients, 1 was in group A, 2 were group B, 7 were in group C, and 1 was in group D. Results : There were 87 NPEV infections, including 11 EV71 infections. The mean age of the patients was 2 years and 11 months, ranging from 1 day to 15 years. There were no fatal cases among a total of 87 NPEV infections and no significant differences in clinical severity between the EV71 and other NPEV infections. Conclusion : NPEV infections in children were common during the 3 months in the spring of 2000. Unlike in southeast Asia, where fatal EV71 infection outbreaks have occurred since 1997, the clinical features of EV71 infection in Korean children are mild.