• Pediatric Infection and Vaccine
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• 제17권2호
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• pp.122-129
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• 2010

목적 : 장바이러스 감염은 소아에서 흔하게 일어나며 무균성 수막염, 수족구병, 포진성 구협염, 신생아 감염, 결막염 등의 원인이 된다. 특히 enterovirus 71형에 의한 감염은 증가하고 있으며 국내에서도 치명적인 사례가 보고되고 있어 본 저자들은 장바이러스의 임상 양상을 분석하고 그 중 enterovirus 71형으로 감염된 환아들의 임상 양상을 비교 분석하고자 하였다. 방법 : 2009년 5월 1일부터 8월 31일까지 신촌 세브란스병원 소아청소년과 외래를 방문하거나 입원한 환자중 장바이러스 감염이 의심된 63명의 환아를 대상으로 급성기에 뇌척수액 또는 분변을 채취하여 질병관리본부에 의뢰하여 혈청형을 분석하였다. 그리고 장바이러스가 배양된 환아를 대상으로 성별, 연령. 임상양상 등을 비교 분석하였다. 결과 : 임상적으로 장바이러스 감염이 의심된 63명 중 38명(60%)에서 양성을 보였다. 양성 환아의 평균 연령은 2년 7개월 이고 성별은 남아 18명, 여아 20명으로 남녀비는 0.9:1 이었다. 장바이러스 감염의 임상증상은 발열(95%). 발진(39%), 식욕부진(24%), 구토와 복통의 소화기 증상(18%), 두통(16%), 기침, 콧물의 호흡기 증상(13%)이 나타났다. 장바이러스 감염은 무균성 수막염(55%), 수족구병(42%). 포진성 구협염(13%), 신생아 감염(5%), 뇌염(3%), 심근염(3%)이 있었다. 분리된 장바이러스는 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 A2형 1례, coxsakievirus A형 1례, 미분류 장바이러스 2례가 보고 되었고, 신생아 감염은 coxsakievirus 2례, 뇌염과 심근염에서 enterovirus 71형이 1례씩 검출되었다. Enterovirus 71형 감염이 확인된 8명은 남아 6명, 여아 2명으로 남녀비는 3:1 이고 발열(88%), 발진(63%), 식욕부진(50%)의 증상을 보였다. Enterovirus 71형의 감염은 수족구병은 5례, 무균성 수막염 3례, 뇌염, 심근염이 1례씩 있었다. Enterovirus 71형과 다른 장바이러스의 혈액검사는 CRP 에서 enterovirus 71형이 양성률이 높았고 다른 혈액학적 검사와 뇌척수액 검사는 통계학적으로 유의한 차이는 없었다. 결론 : 2009년 5월과 8월에 다양한 장바이러스가 유행하였고 특히 신경계 감염을 초례하는 enterovirus 71형도 보고되었다. Enterovirus 71형과 다른 장바이러스 감염과 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.

• Clinical and Experimental Pediatrics
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• 제54권1호
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• pp.11-16
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• 2011

Purpose: Enterovirus 71, one of the enteroviruses that are responsible for both hand-foot-and-mouth disease and herpangina, can cause neural injury. During periods of endemic spread of hand-foot-andmouth disease caused by enterovirus 71, CNS infections are also frequently diagnosed and may lead to increased complications from neural injury, as well as death. We present the results of our epidemiologic research on the clinical manifestations of children with CNS infections caused by enterovirus 71. Methods: The study group consisted of 42 patients admitted for CNS infection by enterovirus 71 between April 2009 and October 2009 at the Department of Pediatrics of 5 major hospitals affiliated with the Catholic University of Korea. We retrospectively reviewed initial symptoms and laboratory findings on admission, the specimen from which enterovirus 71 was isolated, fever duration, admission period, treatment and progress, and complications. We compared aseptic meningitis patients with encephalitis patients. Results: Of the 42 patients (23 men, 19 women), hand-foot-and-mouth disease was most prevalent (n=39), followed by herpangina (n=3), upon initial clinical diagnosis. Among the 42 patients, 15 (35.7%) were classified as severe, while 27 (64.3%) were classified as mild. Factors such as age, fever duration, presence of seizure, and use of intravenous immunoglobulin (IVIG) were statistically different between the 2 groups. Conclusion: Our results indicate that patients with severe infection caused by enterovirus 71 tended to be less than 3 years old, presented with at least 3 days of fever as well as seizure activity, and received IVIG treatment.

• Pediatric Infection and Vaccine
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• 제10권1호
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• pp.114-122
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• 2003

본 저자들은 상기도 감염 후 발열과 배뇨곤란, 하지의 근력저하를 주소로 내원한 7세 환아에서, 급성 횡단성 척수염 증상으로 시작하여 의식 변화와 호흡부전의 급성 파종성 뇌척수염으로 진행한 1례에서 enterovirus 71을 증명하고 고용량 methylprednisolone 정주 후 증상의 호전을 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

• Clinical and Experimental Pediatrics
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• 제59권10호
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• pp.395-401
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• 2016

Since the outbreak of the enterovirus 71 (EV71) infection in Malaysia in 1997, large epidemics of EV71 have occurred in the Asia-Pacific region. Many children and infants have died from serious neurological complications during these epidemics, and EV71 infection has become a serious public health problem in these areas. EV71 infection causes hand, foot and mouth disease (HFMD) in children, and usually resolves spontaneously. However, EV71 occasionally involves the central nervous system (CNS), and induces diverse neurological complications such as brainstem encephalitis, aseptic meningitis, and acute flaccid paralysis. Among those complications, brainstem encephalitis is the most critical neurological manifestation because it can cause neurogenic pulmonary hemorrhage/edema leading to death. The characteristic clinical symptoms such as myoclonus and ataxia, cerebrospinal fluid (CSF) pleocytosis, and brainstem lesions on magnetic resonance imaging, in conjunction with the skin rash of HFMD and the isolation of EV71 from a stool, throat-swab, or CSF sample are typical findings indicating CNS involvement of EV71 infection. Treatment with intravenous immunoglobulin and milrinone are recommended in cases with severe neurological complications from EV71 infection, such as brainstem encephalitis. Despite the recent discovery of receptors for EV71 in human cells, such as the scavenger receptor B2 and P-selection glycoprotein ligand 1, it is not known why EV71 infection predominantly involves the brainstem. Recently, 3 companies in China have completed phase III clinical trials of EV71 vaccines. However, the promotion and approval of these vaccines in various countries are problems yet to be resolved.

• Journal of Applied Biological Chemistry
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• 제51권3호
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• pp.123-127
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• 2008

Anti-enterovirus 71 (EV 71) activities of fifteen herb plant species extracts were examined by SRB assay, among which Origanum vulgare and Rosmarinus officinalis (Anna Rosemary) extracts exhibited the activities with $IC_{50}$ of 8.28 and $8.17\;{\mu}g/mL$, respectively. Their 50% cytotoxicity concentrations ($CC_{50}$) were 691.89 and $1104.19\;{\mu}g/mL$, and the therapeutic indices were 83.56 and 135.15, respectively. Amantadine (positive control) showed anti-EV 71 activity with 50% inhibitory concentration and $CC_{50}$ of 4.46 and $145.22\;{\mu}g/mL$, respectively. Addition of the methanol extracts of O. vulgare and R. officinalis (Anna Rosemary) in EV 71-infected Vero cells strongly inhibited the formation of visible cytopathic effects without changing the normal morphology of the cells. These results indicate that methanol extracts of O. vulgare and R. officinalis (Anna Rosemary) may contain antiviral compound inhibiting the EV 71 replication.

• Clinical and Experimental Pediatrics
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• 제55권10호
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• pp.359-366
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• 2012

Although most enterovirus infections are not serious enough to be life threatening, several enteroviruses such as enterovirus 71 are responsible for severe, potentially life-threatening disease. The epidemic patterns of enteroviruses occur regularly during the year, but they may change due to environmental shifts induced by climate change due to global warming. Therefore, enterovirus epidemiological studies should be performed continuously as a basis for anti-viral studies. A great number of synthesized antiviral compounds that work against enteroviruses have been developed but only a few have demonstrated effectiveness in vivo. No proven effective antiviral agents are available for enterovirus disease therapy. The development of a new antiviral drug is a difficult task due to poor selective toxicity and cost. To overcome these limitations, one approach is to accelerate the availability of other existing antiviral drugs approved for antiviral effect against enteroviruses, and the other way is to screen traditional medicinal plants.

• Pediatric Infection and Vaccine
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• 제30권2호
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• pp.91-96
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• 2023

Enterovirus (EV) 71은 무균성 뇌수막염 환자로부터 처음 분리된 이후로 주로 수족구병으로 나타났으며 소아에서 전형적인 피부 발진, 구강 병변 및 발열을 동반한다. 피부 발진은 수포성으로 손과 발에 영향을 미치고 수포가 없는 반구진 양상일 수도 있으며 특히 어린 소아 및 유아에서는 팔꿈치, 무릎 그리고 엉덩이를 침범할 수도 있다. EV 71 감염으로 인한 신경학적 합병증은 매우 드물지만 주로 뇌간 뇌염으로 나타난다. 대근육 운동 발달 지연 이외에 건강했던 30개월 된 남아가 발열, 혼수 증상으로 내원하였고 입원 후 무호흡 및 호흡 정지 증상이 동반되어 뇌척수액 검사 및 뇌 MRI, 뇌파검사를 하였다. 검사 결과 뇌간 뇌염 및 미만성 대뇌 기능 장애가 확인되었고 비인두도말 및 대변 검체에서 EV 71이 검출되었으며 유전자 검사에서 myoclonic epilepsy with ragged red fiber syndrome이 확인되었다. 저자들은 기저미토콘드리아 질환으로 인해 인후 및 피부 발진의 증상 없이 발열 하루 만에 빠르게 진행되는 EV 71 감염으로 인한 뇌간 뇌염 1예를 보고하는 바이다.

• Clinical and Experimental Vaccine Research
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• 제12권4호
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• pp.291-297
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• 2023

Enterovirus infections induce infectious diseases in young children, such as hand, foot, and mouth disease which is characterized by highly contagious rashes or blisters around the hands, feet, buttocks, and mouth. This predominantly arises from enterovirus A71 or coxsackievirus A16 infections and in severe cases, they can lead to encephalitis, paralysis, pulmonary edema, or even fatality, representing a global health threat. Due to the absence of effective therapeutic strategies for these infections, various experimental animal models are being investigated for the development of vaccines. During the early stages of research on enterovirus infections, non-human primate infections exhibited symptoms like those in humans, leading to their utilization as model animals. However, due to economic and ethical considerations, their current usage is limited. While enterovirus infections do not readily occur in mice, an infection model with mouse-adapted strain in neonatal mice has been employed. Cellular receptors have been identified in human cells, and genetically modified mice expressing these receptors have been used. Most recently, the utilization of Mongolian gerbil model is actively being considered and should be pursued for further animal model development. So, herein, we provide a summarized overview of the current portfolio of available enterovirus infection models, emphasizing their respective advantages and limitations.

• Pediatric Infection and Vaccine
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• 제20권2호
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• pp.81-88
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• 2013

목 적 : 본 연구는 최근 5년간 엔테로바이러스의 분자유전학적 역학 및 임상 양상을 조사하고자 하였다. 방 법 : 2006년부터 2010년까지 한전병원에서 엔테로바이러스 감염이 의심되는 소아 환자의 검체를 질병관리본부로 의뢰하였고, 감염이 확진된 환자를 후향적으로 분석하였다. 결 과 : 277명 환자에서 386개의 검체가 분석되었고 그 중 적어도 한 개 이상의 검체에서 양성을 소견을 보인 환자는 총 98명(35.4%) 이었다. 98명의 환자로부터 100개의 엔테로바이러스가 확인되었고, echovirus 30형 28건(28%), enterovirus 71형 12건(12%), echovirus 25형 10건(10%), echovirus 9형 9건(9%), coxsackievirus A6형 8건(8%) 순이었다. 연도별 분포는 2006년과 2008년에 각각 echovirus 25형 및 echovirus 30형에 의한 무균성 뇌수막염이 각각 61.5% 및 69.2%로 대부분을 차지하였다. Enterovirus 71형에 의한 합병증을 동반한 환자는 없었다. 결 론 : 단일기관에서 최근 5년간 분리된 엔테로바이러스 감염 양상을 확인하였고 우리나라 소아에서의 최근 역학을 파악하는 데 도움이 될 것으로 사료된다.

• Clinical and Experimental Pediatrics
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• 제53권5호
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• pp.616-622
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• 2010

Enterovirus 71 (EV71) has been recognized as a frequent cause of epidemics of hand-foot-and-mouth disease (HFMD) associated with severe neurological symptoms. In the spring of 2009, HFMD was epidemic in Korea. Severe cases with complication, including death, have been reported and it has become a public health issue. Most symptomatic EV71 infections commonly result in HFMD or herpangina. These clinical manifestations can be associated with neurologic syndromes frequently. Neurologic syndromes observed in EV71 include meningitis, meningoencephalomyelitis, poliomyelitis-like paralytic disease, Guillain-Barr$\acute{e}$ syndrome, transverse myelitis, cerebellar ataxia, opsoclonus-myoclonus syndrome, benign intracranial hypertension, and brainstem encephalitis. Examinations for EV 71 were performed from the stools, respiratory secretion or CSF of the children by realtime PCR. Gene analysis showed that most of them were caused by EV71 subgenotype C4a which was prevalent in China, 2008. Public health measures including personal and environmental hygiene, must to target daycare centers, kindergartens, and schools where highly susceptible children congregate. To prevent the spread of infection, preschools where transmission persists for more than 2 incubation periods, have been recommended for closure, and trigger criteria for voluntary closure was instituted. During closure, operators are to thoroughly clean the centers before they are allowed to reopen. In addition, parents are advised to ensure that their children adopt a high standard of personal hygiene and to keep the infected child at home until full recovery. Because the outbreaks occur in a cyclical pattern, surveillance system to predict next outbreaks and adequate public health measures to control need to be planned for future. Control of EV71 epidemics through surveillance and public health intervention needs to be maintained in Korea. Future research should focus on understanding of EV71 virulence, identification of the receptor(s) for EV71, development of antiviral agents and development of vaccine.