{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T17:30:07Z","timestamp":1781976607880,"version":"3.54.5"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,6]],"date-time":"2023-05-06T00:00:00Z","timestamp":1683331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["16H05360"],"award-info":[{"award-number":["16H05360"]}]},{"name":"Japan Society for the Promotion of Science","award":["20K10455"],"award-info":[{"award-number":["20K10455"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP22fk01081222"],"award-info":[{"award-number":["JP22fk01081222"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP22wm0225006"],"award-info":[{"award-number":["JP22wm0225006"]}]},{"name":"Japan Agency for Medical Research and Development","award":["16H05360"],"award-info":[{"award-number":["16H05360"]}]},{"name":"Japan Agency for Medical Research and Development","award":["20K10455"],"award-info":[{"award-number":["20K10455"]}]},{"name":"Japan Agency for Medical Research and Development","award":["JP22fk01081222"],"award-info":[{"award-number":["JP22fk01081222"]}]},{"name":"Japan Agency for Medical Research and Development","award":["JP22wm0225006"],"award-info":[{"award-number":["JP22wm0225006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Many different enteric viruses can cause acute gastroenteritis in humans worldwide. While a single virus can indeed cause disease, multiple-virus infections are commonly reported. However, data regarding a comparison between single- and multiple-virus infections upon clinical manifestations of acute gastroenteritis are relatively limited. In this study, a total of 2383 fecal specimens were collected from children with acute gastroenteritis during June 2014\u2013July 2017 in a pediatric clinic in Japan and tested for 11 viruses by multiplex RT-PCR. At least 1 virus was found in 1706 (71.6%) specimens and norovirus GII was the most frequent agent, followed by rotavirus A and other viruses. Multiple-virus infections were identified in 565 cases (33.1%). While major clinical symptoms were found to be significantly different in some single- vs. multiple-virus infections, the disease severity was statistically non-significant. Our study highlights the burden of multiple-virus infections for acute gastroenteritis and the clinical features of patients with multiple-virus infections.<\/jats:p>","DOI":"10.3390\/ijms24098364","type":"journal-article","created":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T03:34:53Z","timestamp":1683516893000},"page":"8364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Comparative Study of Acute Gastroenteritis Symptoms in Single- versus Multiple-Virus Infections"],"prefix":"10.3390","volume":"24","author":[{"given":"Toshiyuki","family":"Hikita","sequence":"first","affiliation":[{"name":"Hikita Pediatric Clinic, Kiryu City 376-0035, Gunma, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tung","family":"Phan","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2206-282X","authenticated-orcid":false,"given":"Shoko","family":"Okitsu","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Bunkyo City 113-8602, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-1443","authenticated-orcid":false,"given":"Satoshi","family":"Hayakawa","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Bunkyo City 113-8602, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ushijima","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Bunkyo City 113-8602, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,6]]},"reference":[{"key":"ref_1","unstructured":"GBD 2017 Diarrhoeal Disease Collaborators (2020). Quantifying risks and interventions that have affected the burden of diarrhoea among children younger than 5 years: An analysis of the Global Burden of Disease Study 2017. Lancet Infect. Dis., 20, 37\u201359."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.pop.2013.05.006","article-title":"Acute gastroenteritis","volume":"40","author":"Graves","year":"2013","journal-title":"Prim. Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"247262","DOI":"10.1046\/j.1469-0691.2003.00560.x","article-title":"Viruses causing gastroenteritis","volume":"9","author":"Wilhelmi","year":"2003","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1017\/S0950268820000618","article-title":"Enteric pathogens associated with gastroenteritis among children under 5 years in sub-Saharan Africa: A systematic review and meta-analysis","volume":"148","author":"Oppong","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.gtc.2021.02.003","article-title":"Viral acute gastroenteritis in special populations","volume":"50","author":"Meier","year":"2021","journal-title":"Gastroenterol. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0140-6736(18)31128-0","article-title":"Viral gastroenteritis","volume":"392","author":"Estes","year":"2018","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Omatola, C.A., and Olaniran, A.O. (2022). Rotaviruses: From pathogenesis to disease control\u2014A critical review. Viruses, 14.","DOI":"10.3390\/v14050875"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sridhar, A., Karelehto, E., Brouwer, L., Pajkrt, D., and Wolthers, K.C. (2019). Parechovirus A pathogenesis and the enigma of genotype A-3. Viruses, 11.","DOI":"10.3390\/v11111062"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1002\/jmv.24630","article-title":"Detection and characterization of Aichi virus 1 in pediatric patients with diarrhea in Thailand","volume":"89","author":"Chuchaona","year":"2017","journal-title":"J. Med. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/1743-422X-11-182","article-title":"Epidemiology of human parechovirus, Aichi virus and salivirus in fecal samples from hospitalized children with gastroenteritis in Hong Kong","volume":"11","author":"Yip","year":"2014","journal-title":"Virol. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s40249-016-0157-2","article-title":"Impact of co-infections with enteric pathogens on children suffering from acute diarrhea in southwest China","volume":"5","author":"Zhang","year":"2016","journal-title":"Infect. Dis. Poverty"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104513","DOI":"10.1016\/j.jcv.2020.104513","article-title":"Assessing the burden of viral co-infections in acute gastroenteritis in children: An eleven-year-long investigation","volume":"129","author":"Bonura","year":"2020","journal-title":"J. Clin. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.meegid.2018.02.011","article-title":"Detection and molecular characterization of enteric viruses in children with acute gastroenteritis in Northern Italy","volume":"60","author":"Biscaro","year":"2018","journal-title":"Infect. Genet. Evol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1002\/jmv.25399","article-title":"Epidemiology of enteric viruses in children with gastroenteritis in Ogun State, Nigeria","volume":"91","author":"Arowolo","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/jmv.20857","article-title":"Diversity of viruses associated with acute gastroenteritis in children hospitalized with diarrhea in Ho Chi Minh City, Vietnam","volume":"79","author":"Nguyen","year":"2007","journal-title":"J. Med. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e285","DOI":"10.1097\/INF.0b013e31828c3de4","article-title":"Viral agents associated with acute diarrhea among outpatient children in southeastern China","volume":"32","author":"Chen","year":"2013","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1002\/jmv.25645","article-title":"Epidemiology and clinical features of rotavirus, adenovirus, and astrovirus infections and coinfections in children with acute gastroenteritis prior to rotavirus vaccine introduction in Meerut, North India","volume":"92","author":"Akdag","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jcv.2018.12.004","article-title":"Viral gastroenteritis among children of 0-5 years in Nigeria: Characterization of the first Nigerian aichivirus, recombinant noroviruses and detection of a zoonotic astrovirus","volume":"111","author":"Japhet","year":"2019","journal-title":"J. Clin. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s00705-015-2387-1","article-title":"Molecular characterization and multiple infections of rotavirus, norovirus, sapovirus, astrovirus and adenovirus in outpatients with sporadic gastroenteritis in Shanghai, China, 2010\u20132011","volume":"160","author":"Lu","year":"2015","journal-title":"Arch. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.7883\/yoken.JJID.2020.069","article-title":"Prevalence of eleven infectious viruses causing diarrhea in Korea","volume":"73","author":"Kim","year":"2020","journal-title":"Jpn. J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ou\u00e9draogo, N., Kaplon, J., Bonkoungou, I.J., Traor\u00e9, A.S., Pothier, P., Barro, N., and Ambert-Balay, K. (2016). Prevalence and genetic diversity of enteric viruses in children with diarrhea in Ouagadougou, Burkina Faso. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153652"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Makimaa, H., Ingle, H., and Baldridge, M.T. (2020). Enteric viral co-infections: Pathogenesis and perspective. Viruses, 12.","DOI":"10.3390\/v12080904"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/QCO.0000000000000447","article-title":"When do co-infections matter?","volume":"31","author":"McArdle","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e00111-17","DOI":"10.1128\/CMR.00111-17","article-title":"Virological and immunological outcomes of coinfections","volume":"31","author":"Kumar","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"664386","DOI":"10.3389\/fmicb.2021.664386","article-title":"Co-infections as modulators of disease outcome: Minor players or major players?","volume":"12","author":"Devi","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1002\/jmv.24155","article-title":"Four-year study of viruses that cause diarrhea in Japanese pediatric outpatients","volume":"87","author":"Thongprachum","year":"2015","journal-title":"J. Med. Virol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:30:27Z","timestamp":1760124627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/9\/8364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,6]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["ijms24098364"],"URL":"https:\/\/doi.org\/10.3390\/ijms24098364","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,6]]}}}