title: Epidemiology and virologic investigation of human enterovirus 71 infection in the Republic of Korea from 2007 to 2012: a nationwide cross-sectional study.
abstract: Enterovirus (EV) 71 is the main pathogen associated with hand, foot and mouth disease (HFMD) or herpangina. Outbreaks of HFMD caused by EV71 infection are associated severe neurological disease and high mortality rates in children. Several sporadic cases of EV71 infection occurred in the Republic of Korea (ROK) in 2000, and EV71 infections were not reported thereafter until 2006. In this prospective study, we report the epidemic and virologic characteristics of the EV71 endemic from 2007 to 2012 in the Republic of Korea.
  
  
  
  We analyzed characteristics of the EV71 infection-associated epidemic from collected specimens and clinical information from 9987 patients with suspected EV infection from the National EV Surveillance System in ROK. To identify the EV71 subgenotype, the homology of viral protein 1 sequences obtained using reverse transcription polymerase chain reaction was compared with the sequences on other countries available from GenBank database.
  
  
  
  EV71 was detected in 585 (16.7 %) specimens (cerebrospinal fluid, stool or rectal swabs, throat swabs and blood) during study period and was most frequently observed during epidemic seasons in 2009-2012. Major manifestations due to EV71 infection were HFMD (62.2 %) and HFMD with severe neurological complications (28.4 %). Five deaths (0.9 %) due to EV71 infection occurred, with an increased mortality rate during the period after 2009. Most patients (476; 81.4 %) were less than 5 years of age. Analysis of the monthly distribution showed that there was an obvious seasonal pattern to the epidemics, with infections appearing from June to August. The major subgenotype of EV71 isolates circulating in ROK was the C4a strain, which has also appeared in China, Japan and Vietnam.
  
  
  
  This surveillance provided valuable data on the epidemic characteristics of EV71 infections in ROK during a 6-year period. Our findings provide data to assist during future outbreaks of EV71 and associated acute neurologic disease.
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Hyeon
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Seoyeon
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Yong-Pyo
authors.initials: YP
authors.lastname: Lee
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Byunghak
authors.initials: B
authors.lastname: Kang
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea.
authors.forename: Jeong-Bae
authors.initials: JB
authors.lastname: Ahn
authors.affiliation: Department of Biology Graduate School, Kyung Hee University, Seoul, Dongdaemun-gu, 130-701, Republic of Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Jeong
authors.affiliation: Division of Vaccine Research, Center for Infectious Diseases, Korea National Institutes of Health, Korea Centers for Disease Control and Prevention, Osong-eup, Cheongju, Chungcheongbuk-do, 363-951, Republic of Korea. junewoo1213@korea.kr.
authors.forename: June-Woo
authors.initials: JW
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D002555:Cerebrospinal Fluid / Q000821:virology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004196:Disease Outbreaks; D029821:Enterovirus A, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D005243:Feces / Q000821:virology; D005260:Female; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000453:epidemiology* / Q000401:mortality / Q000821:virology; D006801:Humans; D007223:Infant; D008297:Male; D010802:Phylogeny; D012367:RNA, Viral / Q000302:isolation & purification / Q000378:metabolism; D056910:Republic of Korea / Q000453:epidemiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D014764:Viral Proteins
keywords: Foot and mouth disease; Hand; Human enterovirus 71; Neurological complications