{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T20:33:52Z","timestamp":1793997232147,"version":"4.8.0"},"reference-count":93,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2019,10,20]],"date-time":"2019-10-20T00:00:00Z","timestamp":1571529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19fk0108084j0501"],"award-info":[{"award-number":["19fk0108084j0501"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Daido Life Welfare Foundation, Japan","award":["2018-9"],"award-info":[{"award-number":["2018-9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Enteroviruses (EVs) are responsible for extremely large-scale, periodic epidemics in pediatric cohorts, particularly in East and Southeast Asia. Clinical presentation includes a diverse disease spectrum, including hand-foot and mouth disease (HFMD), aseptic meningitis, encephalitis, acute flaccid paralysis, and acute flaccid myelitis. HFMD is predominantly attributable to EV-A types, including the major pathogen EV-A71, and coxsackieviruses, particularly CV-A6, CV-A16, and CV-A10. There have been multiple EV-A71 outbreaks associated with a profound burden of neurological disease and fatal outcomes in Asia since the early 1980s. Efficacious vaccines against EV-A71 have been developed in China but widespread pediatric vaccination programs have not been introduced in other countries. Encephalitis, as a consequence of complications arising from HFMD infection, leads to damage to the thalamus and medulla oblongata. Studies in Vietnam suggest that myoclonus is a significant indicator of central nervous system (CNS) complications in EV-A71-associated HFMD cases. Rapid response in HFMD cases in children is imperative to prevent the progression to a CNS infection; however, prophylactic and therapeutic agents have not been well established internationally, therefore surveillance and functional studies including development of antivirals and multivalent vaccines is critically important to reduce disease burden in pediatric populations.<\/jats:p>","DOI":"10.3390\/ijms20205201","type":"journal-article","created":{"date-parts":[[2019,10,21]],"date-time":"2019-10-21T03:40:29Z","timestamp":1571629229000},"page":"5201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":121,"title":["Enterovirus-Associated Hand-Foot and Mouth Disease and Neurological Complications in Japan and the Rest of the World"],"prefix":"10.3390","volume":"20","author":[{"given":"Gabriel","family":"Gonzalez","sequence":"first","affiliation":[{"name":"Division of Bioinformatics, Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan"},{"name":"National Advanced Computing Collaboratory, National Center for High Technology, San Jose 1174-1200, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Carr","sequence":"additional","affiliation":[{"name":"National Virus Reference Laboratory, School of Medicine, University College Dublin, D04 V1W8 Dublin, Ireland"},{"name":"Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Sapporo 001-0020, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Kobayashi Pediatric Clinic, Fujieda 426-0067, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1039-6278","authenticated-orcid":false,"given":"Nozomu","family":"Hanaoka","sequence":"additional","affiliation":[{"name":"Division 4, Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4861-4349","authenticated-orcid":false,"given":"Tsuguto","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Division 4, Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,20]]},"reference":[{"key":"ref_1","first-page":"490","article-title":"Enteroviruses: Polioviruses, coxsackieviruses, echoviruses, and newer enteroviruses","volume":"Volume 1","author":"Knipe","year":"2007","journal-title":"Fields Virology"},{"key":"ref_2","unstructured":"WHO (2011). 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