{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:54:48Z","timestamp":1791140088702,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Central nervous system (CNS) infections remain a significant public health challenge and require rapid and accurate diagnosis to guide clinical management. Although the incidence of bacterial meningitis has declined owing to widespread vaccination, viral etiologies continue to dominate CNS infections. The aim of this study was to assess the epidemiological trends, age distribution, and seasonality of CNS infections using multiplex PCR. Methods: A retrospective analysis was conducted on cerebrospinal fluid (CSF) samples collected between January 2021 and December 2022 from patients with CNS infections at King Abdulaziz Medical City. A BioFire FilmArray Meningitis\/Encephalitis (ME) panel was used to detect pathogens. Patient demographics, pathogen distribution, and seasonal trends were analyzed. Results: A total of 2460 CSF samples were tested, of which 130 (5%) were positive for at least one pathogen. Viral pathogens accounted for 82.3% of the infections, with human herpesvirus-6 (HHV-6) (31%) and enterovirus (EV) (20%) being the most common. Bacterial pathogens represented 17.7% of the cases, with Streptococcus pneumoniae (6%) and Escherichia coli K1 (5%) being the predominant bacterial agents. The highest infection burden was observed in infants aged 0\u20136 months, with a marked male predominance. Seasonal analysis revealed multiple peaks in viral infections, particularly of HHV-6 and EVs, whereas bacterial infections were sporadic, with Streptococcus agalactiae and Streptococcus pneumoniae peaking in October and November. Conclusions: Viral infections, particularly HHV-6 and EVs, dominated CNS infections, with distinct seasonal and age-related variations. These findings underscore the value of multiplex PCR in improving the rapid diagnosis of CNS infections and aiding in timely treatment and antimicrobial stewardship.<\/jats:p>","DOI":"10.3390\/diagnostics15212699","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T07:31:58Z","timestamp":1761550318000},"page":"2699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unraveling the Burden of Viral and Bacterial Central Nervous System Infections: A Two-Year Retrospective Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-0872","authenticated-orcid":false,"given":"Nabeel","family":"Alzahrani","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Division of Microbiology, Department of Pathology and Laboratory Medicine, Ministry of the National Guard Health Affairs, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Laboratory Medicine, Ministry of the National Guard Health Affairs, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alshehri","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Department of Pathology and Laboratory Medicine, Ministry of the National Guard Health Affairs, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameera","family":"Al Johani","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Division of Microbiology, Department of Pathology and Laboratory Medicine, Ministry of the National Guard Health Affairs, Riyadh 11426, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Layon, A.J., Gabrielli, A., and Friedman, W.A. (2013). Central Nervous System Infections. Textbook of Neurointensive Car, Springer.","DOI":"10.1007\/978-1-4471-5226-2"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Autore, G., Bernardi, L., Perrone, S., and Esposito, S. (2021). Update on Viral Infections Involving the Central Nervous System in Pediatric Patients. Children, 8.","DOI":"10.3390\/children8090782"},{"key":"ref_3","unstructured":"Collaborators GBDM (2018). Global, regional, and national burden of meningitis, 1990\u20132016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 17, 1061\u20131082."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Le Govic, Y., Demey, B., Cassereau, J., Bahn, Y.S., and Papon, N. (2022). Pathogens infecting the central nervous system. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010234"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2372","DOI":"10.1097\/MD.0000000000002372","article-title":"Etiologies and Management of Aseptic Meningitis in Patients Admitted to an Internal Medicine Department","volume":"95","author":"Jarrin","year":"2016","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.emc.2016.06.013","article-title":"Diagnosis and Treatment of Central Nervous System Infections in the Emergency Department","volume":"34","author":"Dorsett","year":"2016","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1128\/JCM.01966-08","article-title":"Eight-plex PCR and liquid-array detection of bacterial and viral pathogens in cerebrospinal fluid from patients with suspected meningitis","volume":"47","author":"Boving","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1128\/JCM.00730-16","article-title":"Multicenter Evaluation of 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":"118","DOI":"10.1016\/j.diagmicrobio.2016.05.020","article-title":"Potential clinical impact of the film array meningitis encephalitis panel in children with suspected central nervous system infections","volume":"86","author":"Messacar","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11908-016-0545-6","article-title":"Laboratory Diagnosis of Central Nervous System Infection","volume":"18","author":"He","year":"2016","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s15010-023-02076-x","article-title":"Multiplex real-time PCR FilmArray performance in the diagnosis of meningoencephalitis: Lights and shadows","volume":"52","author":"Lopez","year":"2024","journal-title":"Infection"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1055\/s-0039-1688441","article-title":"Diagnostic Testing in Central Nervous System Infection","volume":"39","author":"Kanjilal","year":"2019","journal-title":"Semin. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"572","DOI":"10.3855\/jidc.12327","article-title":"Multi-assay investigation of viral etiology in pediatric central nervous system infections","volume":"14","author":"Bozdayi","year":"2020","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Aldriweesh, M.A., Shafaay, E.A., Alwatban, S.M., Alkethami, O.M., Aljuraisi, F.N., Bosaeed, M., and Alharbi, N.K. (2020). Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.602267"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Radmard, S., Reid, S., Ciryam, P., Boubour, A., Ho, N., Zucker, J., Sayre, D., Greendyke, W.G., Miko, B.A., and Pereira, M.R. (2019). Clinical Utilization of the FilmArray Meningitis\/Encephalitis (ME) Multiplex Polymerase Chain Reaction (PCR) Assay. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.00281"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"194","DOI":"10.5858\/arpa.2020-0380-OA","article-title":"Clinical Significance of Positive Results of the BioFire Cerebrospinal Fluid FilmArray Meningitis\/Encephalitis Panel at a Tertiary Medical Center in the United States","volume":"146","author":"Waldrop","year":"2022","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1542\/neo.20-3-e124","article-title":"When to Include a Lumbar Puncture in the Evaluation for Neonatal Sepsis","volume":"20","author":"Aleem","year":"2019","journal-title":"Neoreviews"},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/QCO.0000000000000922","article-title":"Viral meningitis and encephalitis: An update","volume":"36","author":"Gundamraj","year":"2023","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_20","first-page":"580","article-title":"The Worldwide Prevalence of Herpes Simplex Virus Encephalitis and Meningitis: A Systematic Review and Meta-Analysis","volume":"58","author":"Rohani","year":"2023","journal-title":"Turk. Arch. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"ofae501","DOI":"10.1093\/ofid\/ofae501","article-title":"Diagnostic Dilemmas: A Review of Reported Cases of Human Herpesvirus 6 Encephalitis in Immunocompetent Adults","volume":"11","author":"Webb","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e942","DOI":"10.1212\/NXI.0000000000000942","article-title":"Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts","volume":"8","author":"Berzero","year":"2021","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105381","DOI":"10.1016\/j.jcv.2023.105381","article-title":"Disruption of seasonal enterovirus and parechovirus detections in the CSF and plasma of children during the COVID-19 pandemic","volume":"160","author":"Lee","year":"2023","journal-title":"J. Clin. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Johannesen, C.K., Egeskov-Cavling, A.M., Jepsen, M.P.G., Lange, T., Krause, T.G., Nygaard, U., and Fischer, T.K. (2024). Changing rates but persisting seasons: Patterns of enterovirus infections in hospitalizations and outpatient visits in Denmark 2015\u20132022. Front. Virol., 4.","DOI":"10.3389\/fviro.2024.1346352"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6689","DOI":"10.1073\/pnas.1523941113","article-title":"Digital epidemiology reveals global childhood disease seasonality and the effects of immunization","volume":"113","author":"Bakker","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2424802","DOI":"10.1001\/jamanetworkopen.2024.24802","article-title":"Global Case Fatality of Bacterial Meningitis During an 80-Year Period: A Systematic Review and Meta-Analysis","volume":"7","author":"Liechti","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_27","unstructured":"Collaborators GBDMAR (2023). Global, regional, and national burden of meningitis and its aetiologies, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol., 22, 685\u2013711."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Oordt-Speets, A.M., Bolijn, R., van Hoorn, R.C., Bhavsar, A., and Kyaw, M.H. (2018). Global etiology of bacterial meningitis: A systematic review and meta-analysis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198772"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Joshi, Y.P., Kim, E.H., Kim, J.H., Kim, H., and Cheong, H.K. (2016). Associations between Meteorological Factors and Aseptic Meningitis in Six Metropolitan Provinces of the Republic of Korea. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13121193"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T12:07:37Z","timestamp":1761653257000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/21\/2699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,24]]},"references-count":29,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["diagnostics15212699"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15212699","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,24]]}}}