{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:22:03Z","timestamp":1788268923776,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"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>Longitudinal cerebrospinal fluid PCR archives may show apparent age patterns shaped jointly by underlying disease processes and testing architecture. We examined how apparent viral detection patterns varied with denominator choice, target availability, and reconstructed testing configurations among patients tested at a Korean tertiary-care hospital from 2006 to 2026. Clinical diagnoses and adjudication were unavailable, and workflows were reconstructed from reporting configurations rather than definitive platform identifiers. The archive contained 30,481 target-level results from 5353 patient-date episodes in 4560 patients. We summarized per-target positivity, viral-positive composition, and contextual pooled target-level positivity. Human herpesvirus-6 target-level positivity peaked at 31.9% (272\/854) at age 1\u20134 years and comprised 75.8% (91\/120) of infant and 84.0% (272\/324) of 1\u20134-year viral-positive detections. However, HHV-6 was represented in 79.9% and 96.1% of episodes in these groups, whereas enterovirus was represented in only 14.4% and 3.9%. VZV was the most frequently detected adult viral target in the full archive, although rankings varied by period. Apparent age patterns were therefore conditioned by target availability, denominator choice, and evolving workflows and should not be interpreted as clinically adjudicated CNS infection epidemiology.<\/jats:p>","DOI":"10.3390\/pathogens15090905","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:47:13Z","timestamp":1787849233000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Denominator and Workflow Dependence of Age-Specific Viral Detection in Cerebrospinal Fluid"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4554-5824","authenticated-orcid":false,"given":"Ji Yeon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Laboratory Science, College of Health Sciences, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Hyeok-Jin","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science, College of Health Sciences, Dankook University, Cheonan 31116, Republic of Korea"},{"name":"Department of Laboratory Medicine, Ewha Womans University Seoul Hospital, Seoul 07804, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-5705","authenticated-orcid":false,"given":"Jae-Sik","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science, College of Health Sciences, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1534-563X","authenticated-orcid":false,"given":"Jae Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science, College of Health Sciences, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1128\/CMR.00070-09","article-title":"Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis","volume":"23","author":"Brouwer","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/j.cmi.2016.01.007","article-title":"ESCMID guideline: Diagnosis and treatment of acute bacterial meningitis","volume":"22","author":"Cabellos","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1086\/509330","article-title":"Beyond viruses: Clinical profiles and etiologies associated with encephalitis","volume":"43","author":"Glaser","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1212\/WNL.0b013e3181f11d65","article-title":"Challenge of the unknown: A systematic review of acute encephalitis in non-outbreak situations","volume":"75","author":"Granerod","year":"2010","journal-title":"Neurology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1097\/01.inf.0000180471.03702.7f","article-title":"Clinical and epidemiologic characteristics of viral infections in a neonatal intensive care unit during 12 years","volume":"24","author":"Krediet","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1002\/ana.410330607","article-title":"Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications","volume":"33","author":"Suga","year":"1993","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Kim, J.M., Keum, H.R., Kim, S.W., Baek, H.S., Byun, J.C., Kim, Y.K., Kim, S., and Lee, J.M. (2023). Seasonal trends in the prevalence and incidence of viral encephalitis in Korea (2015\u20132019). J. Clin. Med., 12.","DOI":"10.3390\/jcm12052003"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1128\/JCM.00730-16","article-title":"Multicenter evaluation of the BioFire FilmArray Meningitis\/Encephalitis Panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens","volume":"54","author":"Leber","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101275","DOI":"10.1016\/j.eclinm.2022.101275","article-title":"BioFire FilmArray Meningitis\/Encephalitis panel for the aetiological diagnosis of central nervous system infections: A systematic review and diagnostic test accuracy meta-analysis","volume":"44","author":"Tsokani","year":"2022","journal-title":"EClinicalMedicine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cmi.2019.11.016","article-title":"Diagnostic test accuracy of the BioFire\u00ae FilmArray\u00ae Meningitis\/Encephalitis panel: A systematic review and meta-analysis","volume":"26","author":"Tansarli","year":"2020","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e01927-17","DOI":"10.1128\/JCM.01927-17","article-title":"Evaluation of a commercial multiplex molecular panel for diagnosis of infectious meningitis and encephalitis","volume":"56","author":"Liesman","year":"2018","journal-title":"J. Clin. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.jmoldx.2023.08.005","article-title":"Exploring the utility of multiplex infectious disease panel testing for diagnosis of infection in different body sites: A joint report of the Association for Molecular Pathology, American Society for Microbiology, Infectious Diseases Society of America, and Pan American Society for Clinical Virology","volume":"25","author":"Lewinski","year":"2023","journal-title":"J. Mol. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1128\/JCM.02850-15","article-title":"Preclinical assessment of a fully automated multiplex PCR panel for detection of central nervous system pathogens","volume":"54","author":"Hanson","year":"2016","journal-title":"J. Clin. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1007\/s10096-020-03859-y","article-title":"Point-of-care multiplexed diagnosis of meningitis using the FilmArray\u00ae ME panel technology","volume":"39","author":"Vincent","year":"2020","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1007\/s10096-024-04751-9","article-title":"A multicenter evaluation of the QIAstat-Dx meningitis-encephalitis syndromic test kit as compared to the conventional diagnostic microbiology workflow","volume":"43","author":"Boers","year":"2024","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1474-4422(09)70134-6","article-title":"Varicella zoster virus vasculopathies: Diverse clinical manifestations, laboratory features, pathogenesis, and treatment","volume":"8","author":"Gilden","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/QCO.0000000000000647","article-title":"Central nervous system infections produced by varicella zoster virus","volume":"33","author":"Nagel","year":"2020","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s13311-016-0433-7","article-title":"Herpes simplex virus-1 encephalitis in adults: Pathophysiology, diagnosis, and management","volume":"13","author":"Bradshaw","year":"2016","journal-title":"Neurotherapeutics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jcv.2014.03.010","article-title":"HSV Encephalitis Study Group. Herpes simplex virus encephalitis: Clinical manifestations, diagnosis, and outcome in 106 adult patients","volume":"60","author":"Sili","year":"2014","journal-title":"J. Clin. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1093\/cid\/cis031","article-title":"HSV-2 Meningitis Study Group. Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: A double-blind, randomized controlled trial","volume":"54","author":"Aurelius","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1086\/508281","article-title":"Recurrent benign lymphocytic meningitis","volume":"43","author":"Shalabi","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00143-20","DOI":"10.1128\/CMR.00143-20","article-title":"Human herpesviruses 6A and 6B in brain diseases: Association versus causation","volume":"34","author":"Komaroff","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1128\/CMR.00122-14","article-title":"Laboratory and clinical aspects of human herpesvirus 6 infections","volume":"28","author":"Agut","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jcv.2010.02.007","article-title":"Diagnostic assays for active infection with human herpesvirus 6 (HHV-6)","volume":"48","author":"Caserta","year":"2010","journal-title":"J. Clin. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.1073\/pnas.0913586107","article-title":"The latent human herpesvirus 6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro","volume":"107","author":"Arbuckle","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1373\/clinchem.2013.217240","article-title":"Identification of chromosomally integrated human herpesvirus 6 by droplet digital PCR","volume":"60","author":"Sedlak","year":"2014","journal-title":"Clin. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/jmv.20113","article-title":"Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA","volume":"73","author":"Sashihara","year":"2004","journal-title":"J. Med. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1056\/NEJMoa042207","article-title":"A population-based study of primary human herpesvirus 6 infection","volume":"352","author":"Zerr","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/rmv.715","article-title":"Chromosomally integrated human herpesvirus 6: Questions and answers","volume":"22","author":"Pellett","year":"2012","journal-title":"Rev. Med. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.antiviral.2006.04.002","article-title":"Herpes simplex encephalitis: Adolescents and adults","volume":"71","author":"Whitley","year":"2006","journal-title":"Antivir. Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cuesta, G., Puerta-Alcalde, P., Vergara, A., Roses, E., Bosch, J., Casals-Pascual, C., Soriano, A., Marcos, M.A., Sanz, S., and Vila, J. (2024). An assessment of a new rapid multiplex PCR assay for the diagnosis of meningoencephalitis. Diagnostics, 14.","DOI":"10.3390\/diagnostics14080802"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Le Bars, H., Madany, N., Lamoureux, C., Beauruelle, C., Vallet, S., Payan, C., and Pilorge, L. (2023). Evaluation of the performance characteristics of a new POC multiplex PCR assay for the diagnosis of viral and bacterial neuromeningeal infections. Diagnostics, 13.","DOI":"10.3390\/diagnostics13061110"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Toutounji, K., Jreissati, J.T., and Mahfouz, R. (2026). Faster results, better care? Impact of Meningitis\/Encephalitis syndromic panel testing on pathogen detection and hospital outcomes beyond CSF culture: A literature search for diagnosticians. Diagnostics, 16.","DOI":"10.3390\/diagnostics16050691"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s10096-024-04795-x","article-title":"Hybrid capture shotgun sequencing detected unexpected viruses in the cerebrospinal fluid of children with acute meningitis and encephalitis","volume":"43","author":"Launes","year":"2024","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kakouris, V., Kalyva, N., Militsopoulou, M., Stamouli, V., Meletis, G., Kachrimanidou, M., and Paliogianni, F. (2026). Epidemiology of Herpes Simplex and Varicella Zoster Virus-Associated Central Nervous System Infections in Western Greece: A Five-Year Retrospective Analysis. Pathogens, 15.","DOI":"10.3390\/pathogens15010030"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Fortelny, L., and Marschall, M. (2026). The Current Status of Herpesviridae as Major Human Pathogens: A 10-Year Diagnostic Evaluation in Germany. Pathogens, 15.","DOI":"10.3390\/pathogens15060631"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"von Elm, E., Altman, D.G., Egger, M., Pocock, S.J., G\u00f8tzsche, P.C., Vandenbroucke, J.P. (2007). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for reporting observational studies. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040296"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Benchimol, E.I., Smeeth, L., Guttmann, A., Harron, K., Moher, D., Petersen, I., S\u00f8rensen, H.T., von Elm, E., Langan, S.M., and RECORD Working Committee (2015). The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001885"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00620-25","DOI":"10.1128\/spectrum.00620-25","article-title":"A post-implementation evaluation of BioFire FilmArray Meningitis\/Encephalitis panel for pathogen detection in cerebrospinal fluid with a special focus on clinical significance of HHV-6","volume":"14","author":"Perera","year":"2026","journal-title":"Microbiol. Spectr."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:57:37Z","timestamp":1788267457000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":39,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathogens15090905"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15090905","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]}}}