하절기에 발열을 주소로 입원한 3개월 이하의 영아에서 장바이러스 감염

곽지연,조미현,김성은,강석호,김미옥,마상혁,이규만,Kwak, Ji-Yeon,Cho, Mi-Hyun,Kim, Sung-Eun,Kang, Suk-Ho,Kim, Mi-Ok,Ma, Sang-Hyuk,Lee, Kyu-Man 대한소아감염학회 2001 Pediatric Infection and Vaccine Vol.8 No.1

Purpose : Enterovirus is a common cause of aseptic meningitis and nonspecific febrile illness in young children. During the summer and fall months, enterovirus-infected young children are frequently admitted and evaluated to rule out bacterial sepsis and/or meningitis. The purpose of this study was to evaluate the relationship between nonpolio enterovirus infection and febrile illness in infants under 3 months of age during the summer, fall months by using a stool culture to identify the presence of enterovirus. Methods : Patients included febrile infants under 3 months of age admitted to Masan Fatima Hospital for sepsis evaluation from May 1999 to September 1999. Cultures were performed from stool and Cerebrospinal fluid samples and then were tested for enterovirus infection. Viral isolation and serotype identification were performed by cell culture and immunofluorescent testing. Enteroviruses not typed by immunofluorescent testing were confirmed by reverse transcription-polymerase chain reaction. Results : A total of 44 febrile infants were enrolled; of those, 20(45%) were positive for enterovirus. Two enterovirus culture-positive infants had concomitant urinary tract infection and one had Kawasaki disease. All infants infected with an enterovirus recovered without complications. Serotype of 20 enteroviruses were isolated from stool, 3 of echovirus type 9, 1 of echovirus type 11, 1 Coxsachievirus type B4, 15 of untyped enteroviruses. One untyped enterovirus was isolated in the CSF. Conclusion : Nonpolio enterovirus infections are associated with nonspecific febrile illnesses in infants under 3 months of age.

2009년 단일기관에서 확인된 장바이러스 감염의 임상양상 및 특징에 관한 연구

백동원,김정민,김기환,안종균,김동수 대한소아감염학회 2010 Pediatric Infection and Vaccine Vol.17 No.2

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. 목 적 : 장바이러스 감염은 소아에서 흔하게 일어나며무균성 수막염, 수족구병, 포진성 구협염, 신생아 감염,결막염 등의 원인이 된다. 특히 enterovirus 71형에 의한 감염은 증가하고 있으며 국내에서도 치명적인 사례가보고되고 있어 본 저자들은 장바이러스의 임상 양상을분석하고 그 중 enterovirus 71형으로 감염된 환아들의임상 양상을 비교 분석하고자 하였다. 방 법: 2009년 5월 1일부터 8월 31일까지 신촌 세브란스병원 소아청소년과 외래를 방문하거나 입원한 환자중 장바이러스 감염이 의심된 63명의 환아를 대상으로급성기에 뇌척수액 또는 분변을 채취하여 질병관리본부에 의뢰하여 혈청형을 분석하였다. 그리고 장바이러스가배양된 환아를 대상으로 성별, 연령. 임상양상 등을 비교분석하였다. 결 과:임상적으로 장바이러스 감염이 의심된 63명중 38명(60%)에서 양성을 보였다. 양성 환아의 평균 연령은 2년 7개월 이고 성별은 남아 18명, 여아 20명으로남녀비는 0.9:1 이었다. 장바이러스 감염의 임상증상은발열(95%). 발진(39%), 식욕부진(24%), 구토와 복통의 소화기 증상(18%), 두통(16%), 기침, 콧물의 호흡기증상(13%)이 나타났다. 장바이러스 감염은 무균성 수막염(55%), 수족구병(42%). 포진성 구협염(13%), 신생아 감염(5%), 뇌염(3%), 심근염(3%)이 있었다. 분리된장바이러스는 coxsakie B1형 8례(21%), enterovirus 71형 8례(21%), coxsakievirus A16형 2례(6%)였고,coxsakievirus A2형, coxsakievirus A5형, echovirus 9형이 각각 1례씩, 미분류 장바이러스가 17례였다. 무균성 수막염의 원인 바이러스는 coxsakievirus B1형 8례,enterovirus 71형 3례, coxsakievirus A16형 1례,echovirus 9형 1례, 미분류 장바이러스 8례였고 수족구병은 enterovirus 71형 5례, coxsakievirus A16형 1례, 미분류 장바이러스 10례가 검출되었다. 포진성 구협염은 coxsakievirus A16형 1례, coxsakievirus A2형1례, coxsakievirus A형 1례, 미분류 장바이러스 2례가보고 되었고, 신생아 감염은 coxsakievirus 2례, 뇌염과심근염에서 enterovirus 71형이 1례씩 검출되었다. Enterovirus 71형 감염이 확인된 8명은 남아 6명, 여아2명으로 남녀비는 3:1 이고 발열(88%), 발진(63%), 식욕부진(50%)의 증상을 보였다. Enterovirus 71형의 감염은수족구병은 5례, 무균성 수막염 3례, 뇌염, 심근염이 1례씩 있었다. Enterovirus 71형과 다른 장바이러스의 혈액검사는 CRP 에서 enterovirus 71형이 양성률이높았고 다른 혈액학적 검사와 뇌척수액 검사는 통계학적으로 유의한 차이는 없었다. 결 론: 2009년 5월과 8월에 다양한 장바이러스가 유행하였고 특히 신경계 감염을 초례하는 enterovirus 71형도 보고되었다. Enterovirus 71형과 다른 장바이러스감염과 비교할 때 남자에서 더 많이 발생했고 임상적 증상은 차이가 없었으나 중증의 질병이 발생했고 수족구병에서 중추신경계 합병은 더 많이 발생하였다. 앞으로 장바이러스 감염 환아의 진단 및 치료를 위해 지속적인 역학적 연구가 필요할 것으로 생각된다.

장내 바이러스 분리 동정 및 단클론 항체의 항원 인식 능력에 관한 연구

김기순,지영미,안정배,천두성,신수연,정윤석,이지원,윤재득 국립보건연구원 2000 국립보건원보 Vol.37 No.-

엔테로바이러스 실험실 감시 : 1999-2003

지영미,천두성,최우영,안정배,김기순,정윤석,이지원,이강범,노효송,박귀성,이선화,김성한,조경순,김은선,정재근,윤재득,조해월 대한감염학회 2004 감염과 화학요법 Vol.36 No.5

Purpose : We identified the causative viruses from patients with aseptic meningitis, acute hemorrhagic conjunctivitis and other enterovirus-related diseases to understand the epidemiological patterns and prevailing strains of enterovirus infections each year. Materials and Methods : During 1999-2003, we examined 3,260 specimens from 2,939 patients with aseptic meningitis or other clinical manifestations for the presence of enteroviruses by using both cell culture/ neutralisation test and reverse transcription-polymerse chain reaction-sequencing. To investigate the etiological agents which caused an epidemic of acute haemorrhagic conjunctivitis, conjunctival swab samples from acute haemorrhagic conjunctivitis patients showing cytopathic effects in HEp2 cells were tested by enteroviral specific PCR. Results : We identified 603 isolates of enteroviruses (20.5%) among 2,939 cases and 22 serotypes of human enteroviruses were isolated during this 5 year period. Echovirus 13 and coxsackievirus A24 in 2002 and coxsackievirus A9 in 2003 were the first enterovirus to be indentified in Korea since we began the enterovirus surveillance in 1993. While an epidemic of echovirus 13 infection in Korea began in Gwangju and Jeolla province in 2002 and spread to Seoul, Gyunggi, Busan, Ulsan and other regions, echovirus 6 isolates in 2002 were mainly detected in Busan specimens and some Gwangju samples. From the nucleotide sequencing of enteroviral PCR products of conjunctival swab specimens, we found 85% nucleotide homology to coxsackievirus A24 (D90457). Conclusions : We isolated 603 enteroviral isolates among 2939 cases during 1999-2003. Echovirus 13 and coxsackievirus A24 were the first enterovirus to be identified in Korea and caused nationwide epidemics in 2002. 목적 : 1999-2003년 기간 중 국내의 무균성 수막염, 수족구병, 포진성구협염, 급성 출혈성 결막염 등 엔테로바이러스 감염 의심환자로부터 엔테로바이러스 검출하고 유전자 분석을 실시하여 국내에서 유행하는 엔테로바이러스의 형을 확인하고자 하였다. 재료 및 방법 : 동 기간 중 총 2,939건으로부터 3,260개의 검체가 의뢰되었으며 바이러스 분리를 위한 세포배양/중화시험과 유전자 분석을 병행하여 수행하였다. 결과 : 총 2,939건 중 603건(20.5%)에서 바이러스가 분리되었으며 2000년에 엔테로바이러스 71형과 2002년 중 에코바이러스 13형, 콕사키바이러스 A24형 등을 분리하였으며 분리주간 상동성도 99-100%로 같은 유전자형의 바이러스가 국내유행을 일으킨 것을 확인하였다. 결론 : 1999-2003년 중 총 2,939건 중 603건에서 엔테로바이러스를 분리하였으며 특히 2002년 중 무균성 수막염과 급성출혈성 결막염 환자로부터 에코바이러스 13형과 콕사키바이러스 A24형을 국내에서 최초로 분리하였다

장내바이러스 공통항원 부위의 발현 및 분석

이윤성,정윤석,박정구,김기순,지영미,윤재득 국립보건연구원 1998 국립보건원보 Vol.35 No.-

엔테로바이러스 검출을 위한 real-time nucleic acid sequence-based amplification (NASBA), reverse transcription-PCR (RT-PCR) 및 바이러스 배양법의 비교

나영란(Young-Ran Na),조현철(Hyeon-Cheol Joe),이영숙(Young-Suk Lee),빈재훈(Jae-Hun Bin),최홍식(Hong-Sik Cheigh),민상기(Sang-Kee Min) 한국생명과학회 2008 생명과학회지 Vol.18 No.3

본 연구는 무균성수막염 의심환자의 다양한 검체로부터 enterovirus의 진단을 위하여 real-time NASBA, 2 step RT-PCR 시험과 세포배양 시험을 각각 실시하여 각 시험법의 검출율, 특이도, 사용자 편리성, 시험소요 시간, 교차오염의 가능성 등을 비교 검토하였다. 비교시험 결과 전체 292건의 검체로부터 real-time NASBA에서 145건, 세포배양에서 101건, 2 step RT-PCR에서 86건이 양성으로 나타나 real-time NASBA가 가장 검출율이 높은 시험법임을 알 수 있었다. Enterovirus 외의 무균성수막염 원인바이러스에 대한 특이도 비교 시험결과 2 step RT-PCR 시험에서 rhinovirus 10건 중1건이 위양성 반응을 나타내어 다른 시험법에 비해 특이도가 떨어지는 것으로 나타났다. Real-time NASBA는 하나의 튜브에서 증폭과 검출이 동시에 일어나 다른 시험과 비교하여 교차오염의 가능성이 낮으며 또한 시험 소요시간이 5시간 정도로 세포배양(5-14일 소요) 및 2 step RT-PCR(9시간소요) 에 비하여 신속하게 진단할 수 있어 일선병원이나 실험실에서 enterovirus를 검출을 위하여 적용할 수 있을 것으로 사료된다. Rapid detection of enterovirus (EVs) is important in the management of aseptic meningitis. We examined the relative efficiency and specificity of the real-time nucleic acid sequence-based amplification (NASBA) comparing with the established reverse transcription polymerase chain reaction (RT-PCR) and viral culture method which were used for the detection of enterovirus RNA in clinical specimens. Of the total 292 samples, 145 were found to be positive to enterovirus RNA by real-time NASBA, 101 were positive by viral culture, and 86 were positive by RT-PCR. 147 samples and 46 samples were determined to be negative and positive by all methods respectively, but 4 samples were positive only by real-time NASBA. To compare the specificity of each method, various clinical samples which were diagnosed for herpes simplex virus (HSV)-1, HSV-2, adenovirus, mumps, and rhinovirus were applied. Except one rhinovirus sample which was false positive to enterovirus RNA by RT-PCR, the other different samples were negative to all three methods. The real-time NASBA procedure can be completed within 5 hours in contrast with 9 hours for the RT-PCR and 3-14 days for the viral culture. From this study, it was suggested that the real-time NASBA assay could be a standardized, rapid, specific, and sensitive procedure for the detection of enterovirus RNA.

성인 무균성 수막염 환자의 뇌척수액으로부터 Enteroviruses 의 분리

정희진(Hee Jin Cheong),김우주(Woo Joo Kim),김민자(Min Ja Kim),박승철(Seung Chull Park) 대한내과학회 1997 대한내과학회지 Vol.53 No.4

Background: The enteroviruses are the most common etiologic agent of aseptic meningitis in adults and children. The incidence of enteroviral meningitis in childhood meningitis is up to 80%, but in adults is not known, worldwidely. In Korea, where tuberculosis is endemic, the rapid and accurate diagnostic method for enteroviral meningitis is required especially because early differential diagnosis of viral meningitis from tuberculous meningitis is very important. The aims of this study were the demonstration of enteroviruses from cerebrospinal fluid (CSF) of adult patients with aseptic meningitis by PCR/Southern hybridization and the verification of the usefulness of PCR/southern hybridization as a rapid diagnostic tool. Methods: From July 1992 to June 1995, total 34 CSF samples (10 from children, 24 from adults) of patients with aseptic meningitis were studied. As a control group, 15 patients with tuberculous meningitis and 15 patients with bacterial meningitis were studied. Viral RNA was extracted from CSF, reverse transcriptied into cDNA and amplified. The PCR products were Southern hybridizied with enteroviruses-specific digoxigenin-labelled probe. Results: 16/24(66.7%) samples of adult patients with aseptic meningitis were positive for enteroviruses, while in child patients with aseptic meningitis, 9/10(90%) samples were positive. And in one patient, PCR was positive from asymptomatic, onset-7th day CSF sample. Conclusion: Enteroviruses were the most common causative organisms of adult aseptic meningitis in Korea. And, this study showed the usefulness of PCR/Southern hybridization of enteroviruses from CSF for etiologic diagnosis of adult aseptic meningitis in subclinical, asymptomatic period.

Performance Evaluation of Real-Q Enterovirus Quantification Kit for Enterovirus by Real-time PCR

송두열,김신영,조선아,함형일,황상현,임영태,김형회,장철훈,이은엽 대한진단검사의학회 2010 Annals of Laboratory Medicine Vol.30 No.6

Background : Molecular methods have enabled rapid diagnosis of aseptic meningitis and have reduced both unnecessary therapeutic interventions and medical costs. In this study, we evaluated the analytical performance of the recently developed Real-Q Enterovirus Quantification kit (BioSewoom Inc., Korea). Methods : We evaluated the detection limit, precision, linearity, and cross-reactivity of the Real-Q Enterovirus Quantification kit and compared it with the conventional PCR method. From March to September 2009, we tested 91 CSF specimens from patients who visited the pediatrics department of the university hospital with symptoms of aseptic meningitis or infantile sepsis, and we also tested 48 CSF specimens from patients with febrile convulsion for differential diagnosis. Results : The Real-Q Enterovirus Quantification kit showed good linearity (r=0.997) within a range from 3×102 to 3×1010 copies/mL, and the detection limit of the kit was 83 copies/mL. The withinrun, between-run, and between-day CVs were 5.3-7.6%, 9.5-12.3%, and 11.4-13.4%, respectively. There was no cross reactivity between enteroviruses and various microorganisms. Positive results were obtained for 39.1% (25/64) of the patients suspected of aseptic meningitis and 44.4% (12/27)of the patients suspected of infantile sepsis. However, among the 48 children with febrile conversion, only 4 were positive for enterovirus. Further, the concordance with conventional PCR was high (73/74). Conclusions : The Real-Q Enterovirus Quantification kit showed excellent linearity and high reliability with a broad reportable range. It showed good detection rate when used with clinical specimens and also showed a high concordance with the conventional method. Therefore, this assay would be clinically useful not only in diagnosis of aseptic meningitis but also in differential diagnosis of infantile sepsis. (Korean J Lab Med 2010;30:624-30)

성인 Enterovirus 뇌막염에 대한 치료적 접근과 임상발현

우준희,조용균,김양수 대한화학요법학회 1997 대한화학요법학회지 Vol.15 No.1

목적:성인 장관바이러스 뇌막염의 임상상과 치료방침 등을 분석하기위하여 저자들은 1996년 5월부터 12월까지 서울중앙병원에 입원하였던 무균성뇌막염 환자 28예 가운데 장관바이러스에 의한 뇌막염환자 10례를 대상으로하여 임상연구를 시행하였다. 방법:대상환자의 뇌척수액을 shell vial culture법과 PCR을 이용하여 분리 동정하였으며 임상상과 치료방침은 의무기록을 분석하였다. 결과: 임상증상은 발열 100%, 두통 100%, 전신쇠약 80%, 구토 60%, 설사 20%, 근육통 20%, 식욕부진 10%, 경련 10%로 뇌막염의 특이한 소견은 비교적 드물게 나타났다. 뇌척수액 백혈구수는 평균 318/㎣, 호중구는 평균 24%, 림프구는 편균 62%이었고, 단백은 평균 100㎎/dL로 증가되었는데, ekdd은 평균 64㎎/dL로 정상범위에 속했다. 결론:무균성뇌막염 환자에서 신속한 원인바이러스의 동정은 의료부담을 감축시킬 수 있으며, 성인에서도 무균성뇌막염의 원인으로 장관바이러스는 어린이레서처럼 중요하다. Background : Enterovirus is of the etiologic agents of aseptic meningitis and 85% of pediatric aseptic meningitis was caused by enterovirus. In adults to determine the demographic and clinical characteristics of aseptic meningitis and to evaluate the management tactics, we conducted a comprehensive chart review with virologic studies. Methods : Cerebrospinal fluid from the adult patients with aseptic meningitis was inoculated with precultured fibroblast utilising shell culture. Also simultanenous polymerase chain reaction was performed. Results : Ten adult cases of enterovirus meningitis were identified among twenty-eight cases of aseptic meningitis in which viral isolation was attempted. Analysis of cerebrospinal fluid revealed that an increased total white blood cell count and an increased protein concentration tended to be associated with increasing patient age. Variation in management strategies were noted in the use of computed tomography of the brain, the administration of empirical antimicrobial agents, and duration of hospitalization. Conclusion : Rapid isolation of enterovirus, and a conservative management could have solved the considerable health problem. In adults, Enterovirus is also a main etiologic agent in aseptic meningitis as well as in children.

A Study on Enterovirus Genotypes in Busan, Korea from 2017 to 2022

Nam-Ho Kim,Young-A Jung,Hyeon-Jeong Kwon,Han-Nwi You,이승주 대한미생물학회 2023 Journal of Bacteriology and Virology Vol.53 No.2

Human enteroviruses (HEV) are pathogens that cause a wide variety of clinicalillness such as a hand-foot-mouth disease, herpangina, skin rash, encephalitis,aseptic meningitis and even death in young children. This study was aimed toinvestigate the prevalence of HEV infection in young children in Busan, Korea andanalyze the various genotypes of enterovirus. We collected the stool, throat swaband cerebrospinal fluid samples from admitted pediatrics from 2017 to 2022. HEV detection and genotype identification were performed by real-time RT-PCRand RT-PCR and phylogenetic trees were constructed by neighbor-joining methodcompared with reference strains. A total of 1,412 samples were collected and128 cases (9.1%) were detected. Based on partial VP1 sequencing, a total 93enterovirus isolates were resolved into 4 genotypes and 18 serotypes; Humanenterovirus A, B, D (HEV-A, B, D) and Rhinovirus. HEV-A is 30 isolates included 7serotypes, HEV-B is 63 isolates included 10 serotypes, HEV-D is 1 isolates included1 serotypes and Rhinovirus is 5 isolated included 3 serotypes. Prevalent serotypewas coxsakievirus A10 in 2017, coxsakievirus B5 in 2018, Echovirus 30 in 2019. Thetemporal distribution of HEV epidemics in Busan showed a remarkable seasonalpattern, from June to September. The genotypes of circulating enteroviruseswere diverse from year to year and most of the sequences circulated in Busanshowed homology with reference sequences in neighboring countries such asChina. Monitoring and genotyping of these enteroviruses will play a role inpreventing the development of serious diseases caused by enteroviruses andgenotype analysis can be used as a basic data for epidemiological studies.