{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:26Z","timestamp":1791264086399,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Primary Epstein\u2013Barr virus (EBV) infection in children exhibits substantial clinical heterogeneity, often complicating early diagnosis and leading to unnecessary antibiotic use. This retrospective study evaluated 695 children (0\u201318 years) diagnosed with primary EBV infection at a tertiary pediatric center between 2010 and 2015, defined by positive viral capsid antigen (VCA) IgM and negative Epstein\u2013Barr nuclear antigen (EBNA) IgG. Clinical, laboratory, and ultrasonographic findings were compared according to age group (\u22644 vs. &gt;4 years) and clinical setting (inpatient vs. outpatient). The median age was 3.75 years (IQR: 2\u20136.25), and more than half of the patients were \u22644 years. Younger children more frequently presented with nonspecific respiratory and gastrointestinal symptoms, whereas older children more commonly exhibited the classic infectious mononucleosis (IM) phenotype, including sore throat, dysphagia, lymphadenopathy, and hepatosplenomegaly (p &lt; 0.001). Antibiotics were prescribed in 64.2% of patients, while 21.7% required hospitalization. Multivariable logistic regression analyses demonstrated that age was not an independent predictor of hospitalization, classic IM phenotype, or antibiotic use. Instead, specific clinical and laboratory findings\u2014such as lymphopenia, lymphadenopathy, vomiting, thrombocytosis, and tonsillar hypertrophy\u2014emerged as the key determinants of clinical outcomes. To enhance diagnostic discrimination, receiver operating characteristic (ROC) analysis of ANC\/ALC and AST\/ALT ratios was performed, and a composite risk score (0\u20132) was derived. Although both markers showed modest discriminative ability (AUC 0.607 and 0.575), their high negative predictive values (&gt;90%) suggest potential utility as rule-out tools. The composite score demonstrated a stepwise increase in the probability of classic IM presentation across age groups. In conclusion, primary EBV infection demonstrates a clear age-related clinical spectrum; however, clinical and laboratory features rather than age alone drive key outcomes. These findings highlight the need for age-specific diagnostic strategies and improved antimicrobial stewardship, while the proposed risk score provides a foundation for future validation studies.<\/jats:p>","DOI":"10.3390\/pathogens15050554","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:45:34Z","timestamp":1779291934000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Age-Dependent Clinical Patterns of Primary Epstein\u2013Barr Virus Infection in Children: Insights for Diagnostic Accuracy"],"prefix":"10.3390","volume":"15","author":[{"given":"Demet","family":"Teker-D\u00fczta\u015f","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Dr. Sami Ulus Children\u2019s Health and Diseases Training and Research Hospital, 06080 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"Kaman","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Infectious Disease, Dr. Sami Ulus Children\u2019s Health and Diseases Training and Research Hospital, 06080 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6n\u00fcl","family":"Tan\u0131r","sequence":"additional","affiliation":[{"name":"Departments of Pediatric Infectious Disease, Dr. Sami Ulus Children\u2019s Health and Diseases Training and Research Hospital, 06080 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ye, Z., Chen, L., Zhong, H., Cao, L., Fu, P., and Xu, J. (2023). Epidemiology and clinical characteristics of Epstein-Barr virus infection among children in Shanghai, China, 2017\u20132022. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1139068"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5048","DOI":"10.1002\/jmv.26941","article-title":"Characteristics of primary Epstein-Barr virus infection disease spectrum and its reactivation in children, in Suzhou, China","volume":"93","author":"Shi","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3709","DOI":"10.1002\/jmv.26202","article-title":"Clinical characteristics of primary and reactivated Epstein-Barr virus infection in children","volume":"92","author":"Yang","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jcv.2018.03.001","article-title":"Primary Epstein-Barr virus infection","volume":"102","author":"Dunmire","year":"2018","journal-title":"J. Clin. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/infdis\/jit096","article-title":"Primary Epstein-Barr virus infection: Impact of age at acquisition, coinfection, and viral load","volume":"207","author":"Balfour","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/ped4.12294","article-title":"Clinical characteristics and effectiveness of antiviral agents in hospitalized children with infectious mononucleosis in China: A multicenter retrospective study","volume":"5","author":"Hu","year":"2021","journal-title":"Pediatr. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/09674845.2021.1903683","article-title":"Infectious Mononucleosis: Diagnosis and clinical interpretation","volume":"78","author":"Naughton","year":"2021","journal-title":"Br. J. Biomed. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dowd, J.B., Palermo, T., Brite, J., McDade, T.W., and Aiello, A. (2013). Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6\u201319, 2003\u20132010. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064921"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.12688\/f1000research.15544.1","article-title":"Increasing Epstein-Barr virus infection in Chinese children: A single institutional based retrospective study","volume":"7","author":"Devkota","year":"2018","journal-title":"F1000Research"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"300060520924550","DOI":"10.1177\/0300060520924550","article-title":"Clinical manifestations and laboratory results of 61 children with infectious mononucleosis","volume":"48","author":"Wu","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"368","DOI":"10.24953\/turkjped.2019.03.008","article-title":"Clinical features and laboratory findings in children hospitalized with acute Epstein-Barr virus infection: A crosssectional study in a tertiary care hospital","volume":"61","author":"Caglar","year":"2019","journal-title":"Turk. J. Pediatr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Prtori\u0107, L., \u0160okota, A., Karabati\u0107 Knezovi\u0107, S., Te\u0161ovi\u0107, G., and Zidovec-Lepej, S. (2025). Clinical Features and Laboratory Findings of Hospitalized Children with Infectious Mononucleosis Caused by Epstein-Barr Virus from Croatia. Pathogens, 14.","DOI":"10.3390\/pathogens14040374"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Tian, S., Zheng, J., Zhou, Z., Yang, Q., Sun, B., Li, Y., Lin, Z., Long, Y., Guan, S., and Wang, S. (2025). Retrospective Review of Children Hospitalized for Epstein-Barr Virus-Related Infectious Mononucleosis. Pathogens, 14.","DOI":"10.3390\/pathogens14070702"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"908","DOI":"10.3109\/23744235.2015.1082036","article-title":"Clinical characteristics and laboratory findings in Danish children hospitalized with primary Epstein-Barr virus infection","volume":"47","author":"Topp","year":"2015","journal-title":"Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1440-1827.2006.01936.x","article-title":"Prevalence of Epstein-Barr virus in Japan: Trends and future prediction","volume":"56","author":"Takeuchi","year":"2006","journal-title":"Pathol. Int."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1442-200X.1997.tb03575.x","article-title":"Infectious mononucleosis as a disease of early childhood in Japan caused by primary Epstein-Barr virus infection","volume":"39","author":"Kanegane","year":"1997","journal-title":"Acta Paediatr. Jpn."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gonzalez Saldana, N., Monroy Colin, V.A., Pina Ruiz, G., and Juarez Olguin, H. (2012). Clinical and laboratory characteristics of infectious mononucleosis by Epstein-Barr virus in Mexican children. BMC Res. Notes, 5.","DOI":"10.1186\/1756-0500-5-361"},{"key":"ref_18","first-page":"245","article-title":"Infectious mononucleosis in Turkish children","volume":"52","author":"Cengiz","year":"2010","journal-title":"Turk. J. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/07448481.1988.9939052","article-title":"Epstein-Barr virus infections among university students in a tropical country","volume":"37","author":"Chang","year":"1988","journal-title":"J. Am. Coll. Health"},{"key":"ref_20","first-page":"189","article-title":"Different clinical presentation of infectious mononucleosis in children: A retrospective analysis of 369 cases","volume":"47","author":"Beka","year":"2012","journal-title":"Turk. Arch. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1017\/S0950268803008550","article-title":"Clinical and laboratory presentation of EBV positive infectious mononucleosis in young adults","volume":"131","author":"Grotto","year":"2003","journal-title":"Epidemiol. Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1097\/01.inf.0000095199.56025.96","article-title":"Epstein-Barr virus-associated infectious mononucleosis in Chinese children","volume":"22","author":"Chan","year":"2003","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1542\/peds.75.6.1003","article-title":"Epstein-Barr virus infectious mononucleosis in children. I. Clinical and general laboratory findings","volume":"75","author":"Sumaya","year":"1985","journal-title":"Pediatrics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ejim.2010.07.016","article-title":"Epstein Barr virus hepatitis","volume":"22","author":"Kofteridis","year":"2011","journal-title":"Eur. J. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/coa.13965","article-title":"The utility of liver function tests and abdominal ultrasound in infectious mononucleosis- A systematic review","volume":"47","author":"Tan","year":"2022","journal-title":"Clin. Otolaryngol."},{"key":"ref_26","first-page":"71","article-title":"Infectious Mononucleosis: Rapid Evidence Review","volume":"107","author":"Sylvester","year":"2023","journal-title":"Am. Fam. Physician"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/554\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:57:56Z","timestamp":1779292676000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/5\/554"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["pathogens15050554"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15050554","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]}}}