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인천지역 소아 입원 환자의 엔테로바이러스 역학과 혈청형에 따른 임상양상 비교

Epidemiology and Clinical manifestations of Enterovirus in Pediatric Inpatient in Incheon

  • 조병욱 (인하대학교 의과대학 소아과학교실) ;
  • 권성은 (인하대학교 의과대학 소아과학교실) ;
  • 권문주 (인천광역시 보건환경연구원) ;
  • 허명제 (인천광역시 보건환경연구원) ;
  • 김경선 (인천광역시 보건환경연구원) ;
  • 홍영진 (인하대학교 의과대학 소아과학교실) ;
  • 김순기 (인하대학교 의과대학 소아과학교실) ;
  • 권영세 (인하대학교 의과대학 소아과학교실) ;
  • 김동현 (인하대학교 의과대학 소아과학교실)
  • Cho, Byoung Wook (Department of Pediatrics, Inha University School of Medicine) ;
  • Kwon, Seong Eun (Department of Pediatrics, Inha University School of Medicine) ;
  • Kwon, Mun Ju (Incheon Research Institute of Public Health and Environment) ;
  • Hur, Myong Je (Incheon Research Institute of Public Health and Environment) ;
  • Kim, Kyung Seon (Incheon Research Institute of Public Health and Environment) ;
  • Hong, Young Jin (Department of Pediatrics, Inha University School of Medicine) ;
  • Kim, Soon Ki (Department of Pediatrics, Inha University School of Medicine) ;
  • Kwon, Young Se (Department of Pediatrics, Inha University School of Medicine) ;
  • Kim, Dong Hyun (Department of Pediatrics, Inha University School of Medicine)
  • 투고 : 2015.09.24
  • 심사 : 2015.10.30
  • 발행 : 2016.04.25

초록

목적: 소아에서 엔테로바이러스 감염증은 무증상 감염부터 비특이적 발열성 질환, 수족구병, 수막뇌염 등 다양한 질환으로 나타날 수 있다. 본 연구는 소아 입원 환자들을 대상으로 엔테로바이러스 감염의 유전자형 별 임상양상에 대하여 알아보고자 하였다. 방법: 2014년 3월부터 2015년 3월까지 인하대병원에 입원한 환자들 중 400명을 대상으로 real-time reverse transcriptase-polymerase chain reaction (RT-PCR)로 엔테로바이러스를 검출하였으며, RT-seminested PCR로 혈청형을 분석하였다. 염기서열의 계통분석을 시행하여 neighbor-joining tree를 작성하였다. 결과: 전체 연구대상 400명 중 112명(28%)에서 엔테로바이러스 양성이 확인되었으며 엔테로바이러스 양성 환자의 평균연령은 2.66세(3일-14세), 남녀 성비는 1.73:1 이었다. 65개의 검체에서 엔테로바이러스의 혈청형을 확인할 수 있었고, coxsackievirus B5 17례(15.2%), coxsackievirus A16 13례(11.6%), enterovirus 71 10례(8.9%), coxsackievirus A2 9례(8.0%) 순이었다. 엔테로바이러스 양성 환자들 중 96명(86%)에서 비특이적 발열 증상이 있었으며, 0-11일의 다양한 발열기간을 나타냈고, 평균 발열기간은 3.13일이었다. 발진은 전체 양성환자 중 44명(39%)에서 나타났으며, 수막뇌염은 43명(38%)에서 나타났다. 염기서열에 따른 계통 분석에서 6개의 유전적 군집이 관찰되었다. 결론: 저자들은 인천지역 단일기관에 입원한 환자에서 분리된 엔테로바이러스의 혈청형과 임상양상을 확인하였다. 본 연구 결과가 앞으로 국내 엔테로바이러스 감염의 역학을 파악하는 데에 도움을 줄 것으로 생각한다.

Purpose: Enterovirus (EV) infection in children can manifest various diseases from asymptomatic infection to nonspecific febrile illness, hand-foot-mouth disease, and aseptic meningitis. This study was aimed to investigate epidemiology and clinical significance of various genotypes of EV infections in pediatric inpatient. Methods: We collected the stool samples from the admitted pediatric patients in Inha University Hospital from March 2014 to March 2015. EV detection and genotype identification were performed by real-time RT-PCR and semi-nested RT-PCR. Phylogenetic trees were constructed by neighbor joining method. Results: A total of 400 samples were collected during study period and 112 patients (28%) were diagnosed with EV infections. The mean age of EV positive patients was 2.66 years (0.1-14) and sex ratio was 1.73:1. Genetic sequences of EVs were identified; coxsackievirus B5 (17, 15.2%), coxsackievirus A16 (13, 11.6%), enterovirus 71 (10, 8.9%), and coxsackievirus A2 (9, 8.0%). Nonspecific febrile illness (96, 86%) was the most common clinical manifestation and the duration of fever was 0-11 days (mean 3.1 days). Rash (44, 39%) and meningitis (43, 38%) were followed. Patients who were attending daycare center or had siblings accounted for 82.1%. Phylogenetic relationship tree revealed 6 distinct genogroups among 56 types of EVs. Conclusions: This study is the report of epidemiology, serotype distribution and clinical manifestations of children with EV infection in Incheon. This data will be helpful for further study about the epidemiology of EV infection in Korea.

키워드

참고문헌

  1. Abzug MJ. Nonpolio enteroviruses, In: Kliegman RM, Stanton BF, Schor NF, Geme III JWS, Behrman RE, editors. Nelson textbook of pediatrics. 19th ed. Philadelphia: Elsevier saunders, 2011:1088-94.
  2. Park KS, Choi YJ, Park JS. Enterovirus infection in Korean children and antienteroviral potential candidate agent. Korean J Pediatr 2012;55:359-66.
  3. Modlin JF. Enteroviruses and parechoviruses, In: Long SS, Pickering LK, Prober CG, editors. Principles and practice of pediatric infectious diseases. 4th ed. Philadelphia: Elsevier saunders, 2012:1172-9.
  4. Jee YM, Cheon DS, Choi WY, Ahn JB, Kim KS, Chung YS, et al. Updates on enterovirus surveillance in Korea. Infect Chemother 2004;36:294-303.
  5. Wu Y, Yeo A, Phoon MC, Tan EL, Poh CL, Quak SH, et al. The largest outbreak of hand; foot and mouth disease in Singapore in 2008: the role of enterovirus 71 and coxsackievirus A strains. Int J Infect Dis 2010;14:e1076-81. https://doi.org/10.1016/j.ijid.2010.07.006
  6. Yang F, Ren L, Xiong Z, Li J, Xiao Y, Zhao R, et al. Enterovirus 71 outbreak in the People's Republic of China in 2008. J Clin Microbiol 2009;47:2351-2. https://doi.org/10.1128/JCM.00563-09
  7. Fujimoto T, Iizuka S, Enomoto M, Abe K, Yamashita K, et al. Hand, foot, and mouth disease caused by coxsackievirus A6, Japan, 2011. Emerg Infect Dis 18:337-9.
  8. Infectious Disease Surveillance Center. Virus isolation/detection from hand, foot and mouth disease cases, 2007-2011. Infectious Agents Surveillance Report. Available at: http://idsc.nih.go.jp/iasr/prompt/s2graph-pke.html. Assessed 24 September 2015.
  9. Puenpa J, Mauleekoonphairoj J, Linsuwanon P, Suwannakarn K, Chieochansin T, Korkong S, et al. Prevalence and characterization of enterovirus infections among pediatric patients with hand foot mouth disease, herpangina and influenza like illness in Thailand, 2012. PLoS One 2014;9:e98888. https://doi.org/10.1371/journal.pone.0098888
  10. Korea Centers for Disease Control and Prevention. National laboratory surveillance for enterovirus. Public Health Wkly Rep 2008;1:617-21.
  11. Baek KA, Yeo SG, Lee BH, Park KS, Song JH, Yu JS, et al. Epidemics of enterovirus infection in Chungnam Korea, 2008 and 2009. Virology Journal 2011;8:297. https://doi.org/10.1186/1743-422X-8-297
  12. Park KS, Lee BH, Baek KA, Cheon DS, Yeo SG, Park JS, et al. Enteroviruses isolated from herpangina and hand-foot-andmouth disease in Korean children. Virology Journal 2012;9:205. https://doi.org/10.1186/1743-422X-9-205
  13. Park KS, Choi YJ, Park JS. Enterovirus infection in Korean children and antienteroviral potential candidate agent. Korean J Pediatr 2012;55:359-66.
  14. Seo JH, Yeom JS, Youn HS, Han TH, Chung JY. Prevalence of human parechovirus and enterovirus in cerebrospinal fluid samples in children in Jinju, Korea. Korean J Pediatr 2015;58:102-7. https://doi.org/10.3345/kjp.2015.58.3.102
  15. Park IS, Lee HS, Choi SH, Kim HJ, Hwang SY, Cheon DS, et al. Epidemiology and clinical characteristics of enterovirus infections in children: a single center analysis from 2006 to 2010. Korean J Pediatr Infect Dis 2013;20:81-8. https://doi.org/10.14776/kjpid.2013.20.2.81
  16. Baek DW, Kim JM, Kim KH, Ahn JG, Kim DS. Epidemiologic and clinical features of enteroviral infections in children, a single center study in Korea: 2009. Korean J Pediatr Infect Dis 2010;17:122-9. https://doi.org/10.14776/kjpid.2010.17.2.122
  17. Pöyry T, Kinnunen L, Hyypiä T, Brown B, Horsnell C, Hovi T, et al. Genetic and phylogenetic clustering of enteroviruses. J Gen Virol 1996;77:1699-717. https://doi.org/10.1099/0022-1317-77-8-1699
  18. Ragonnet-Cronin M, Hodcroft E, Hué S, Fearnhill E, Delpech V, Brown AJ, et al. Automated analysis of phylogenetic clusters. BMC Bioinformatics 2013;14:317. https://doi.org/10.1186/1471-2105-14-317
  19. Rosychuk RJ. Identifying geographic areas with high disease rates: when do confidence intervals for rates and a disease cluster detection method agree? Int J Health Geogr 2006;5:46. https://doi.org/10.1186/1476-072X-5-46
  20. Li W, Zhang X, Chen X, Cheng YP, Wu YD, Shu Q, et al. Epidemiology of childhood enterovirus infections in Hangzhou, China. Virol J 2015;12:58. https://doi.org/10.1186/s12985-015-0294-4
  21. Jeon JS, Kim JK, Yu JS, Kim JW. Epidemic trends of enterovirus infections from pediatric patients in Cheonan, Korea. J Clin Lab Anal 2016;30:161-4. https://doi.org/10.1002/jcla.21830
  22. Cherry JD, Harrision GJ, Kaplan SL, Steinbach WJ, Hotez PJ. Enteroviruses, parechoviruses, and saffold viruses, In: Cherry JD, Krogstad P, editors. Feigin and Cherry's textbook of pediatric infectious diseases. 7th ed. Philadelphia: Elsevier saunders, 2014:2051-108.
  23. Witso E, Cinek O, Aldrin M, Grinde B, Rasmussen T, Wetlesen T, et al. Predictors of sub-clinical enterovirus infections in infants: a prospective cohort study. Int J Epidemiol 2010;39:459-68. https://doi.org/10.1093/ije/dyp333
  24. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 1987;4:406-25.
  25. Zhang S, Zhao J. Spatio-temporal epidemiology of hand, foot and mouth disease in Liaocheng City, North China. Exp Ther Med 2015;9:811-6. https://doi.org/10.3892/etm.2015.2207