{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T18:44:10Z","timestamp":1740163450495,"version":"3.37.3"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,23]],"date-time":"2017-11-23T00:00:00Z","timestamp":1511395200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,23]],"date-time":"2017-11-23T00:00:00Z","timestamp":1511395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Encephalitis causes significant global morbidity and mortality. A large number of viruses cause encephalitis, and their geographic and temporal distributions vary. In many encephalitis cases, the virus cannot be detected, even after extensive testing. This is one challenge in management of the encephalitis patient. Since cytokines are pivotal in any form of inflammation and vary according to the nature of the inflammation, we hypothesized cytokine levels would allow us to discriminate between encephalitis caused by viruses and other aetiologies. This pilot study was conducted in a tertiary care hospital in Dhaka, Bangladesh. Viral detection was performed by polymerase chain reaction using patient cerebrospinal fluid. Acute phase reactants and cytokines were detected in patient serum. Of the 29 biomarkers assessed using the Wilcoxon rank-sum test, only vascular endothelial growth factor (VEGF) was significantly higher (P\u2009=\u20090.0015) in viral-positive compared with virus\u2013negative encephalitis patients. The area under the curve (AUC) for VEGF was 0.82 (95% confidence interval: 0.66\u20130.98). Serum VEGF may discriminate between virus-positive and virus-negative encephalitis. Further study will be needed to confirm these findings.<\/jats:p>","DOI":"10.1038\/s41598-017-16474-3","type":"journal-article","created":{"date-parts":[[2017,11,17]],"date-time":"2017-11-17T16:00:41Z","timestamp":1510934441000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased serum vascular endothelial growth factor is associated with acute viral encephalitis in Bangladeshi children"],"prefix":"10.1038","volume":"7","author":[{"given":"Daisuke","family":"Mori","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wahida","family":"Khanam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rahamot Ali","family":"Sheikh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. M. Shahnawaz Bin","family":"Tabib","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emi","family":"Ikebe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Moshaddeque","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidekatsu","family":"Iha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1869-3701","authenticated-orcid":false,"given":"Kamruddin","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,11,23]]},"reference":[{"key":"16474_CR1","doi-asserted-by":"publisher","unstructured":"Granerod, J., Cousens, S., Davies, N. W., Crowcroft, N. S. & Thomas, S. L. New estimates of incidence of encephalitis in England. Emerg Infect Dis \n                           19, https:\/\/doi.org\/10.3201\/eid1909.130064 (2013).","DOI":"10.3201\/eid1909.130064"},{"key":"16474_CR2","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1086\/341301","volume":"35","author":"N Khetsuriani","year":"2002","unstructured":"Khetsuriani, N., Holman, R. C. & Anderson, L. J. Burden of encephalitis-associated hospitalizations in the United States, 1988-1997. Clin Infect Dis \n                           35, 175\u2013182, https:\/\/doi.org\/10.1086\/341301 (2002).","journal-title":"Clin Infect Dis"},{"key":"16474_CR3","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/1743-422X-5-134","volume":"5","author":"F Jmor","year":"2008","unstructured":"Jmor, F., Emsley, H. C., Fischer, M., Solomon, T. & Lewthwaite, P. The incidence of acute encephalitis syndrome in Western industrialised and tropical countries. Virol J \n                           5, 134, https:\/\/doi.org\/10.1186\/1743-422X-5-134 (2008).","journal-title":"Virol J"},{"key":"16474_CR4","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.3201\/eid1509.081540","volume":"15","author":"C Huppatz","year":"2009","unstructured":"Huppatz, C. et al. Etiology of encephalitis in Australia, 1990\u20132007. Emerg Infect Dis \n                           15, 1359\u20131365, https:\/\/doi.org\/10.3201\/eid1509.081540 (2009).","journal-title":"EmergInfect Dis"},{"key":"16474_CR5","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.3201\/eid1909.121855","volume":"19","author":"M Kakkar","year":"2013","unstructured":"Kakkar, M. et al. Acute encephalitis syndrome surveillance, Kushinagar district, Uttar Pradesh, India, 2011-2012. Emerg Infect Dis \n                           19, 1361\u20131367, https:\/\/doi.org\/10.3201\/eid1909.121855 (2013).","journal-title":"EmergInfect Dis"},{"key":"16474_CR6","doi-asserted-by":"publisher","first-page":"e854","DOI":"10.1371\/journal.pntd.0000854","volume":"4","author":"VT Le","year":"2010","unstructured":"Le, V. T. et al. Viral etiology of encephalitis in children in southern Vietnam: results of a one-year prospective descriptive study. PLoS Negl Trop. Dis \n                           4, e854, https:\/\/doi.org\/10.1371\/journal.pntd.0000854 (2010).","journal-title":"PLoS NeglTrop. Dis"},{"key":"16474_CR7","doi-asserted-by":"publisher","first-page":"e141","DOI":"10.1016\/j.ijid.2009.03.035","volume":"14","author":"FK Beig","year":"2010","unstructured":"Beig, F. K., Malik, A., Rizvi, M., Acharya, D. & Khare, S. Etiology and clinico-epidemiological profile of acute viral encephalitis in children of western Uttar Pradesh, India. Internat. J Infect Dis s \n                           14, e141\u2013146, https:\/\/doi.org\/10.1016\/j.ijid.2009.03.035 (2010).","journal-title":"Internat. J Infect Dis s"},{"key":"16474_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/srep02382","volume":"3","author":"A Giri","year":"2013","unstructured":"Giri, A. et al. Aetiologies of central nervous system infections in adults in Kathmandu, Nepal: a prospective hospital-based study. Sci Rep \n                           3, 2382, https:\/\/doi.org\/10.1038\/srep02382 (2013).","journal-title":"Sci Rep"},{"key":"16474_CR9","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1093\/cid\/cir957","volume":"54","author":"MT Mitui","year":"2012","unstructured":"Mitui, M. T. et al. Detection of human bocavirus in the cerebrospinal fluid of children with encephalitis. Clin Infect Dis \n                           54, 964\u2013967, https:\/\/doi.org\/10.1093\/cid\/cir957 (2012).","journal-title":"Clin Infect Dis"},{"key":"16474_CR10","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.3201\/eid1911.121548","volume":"19","author":"D Mori","year":"2013","unstructured":"Mori, D. et al. Human bocavirus in patients with encephalitis, Sri Lanka, 2009-2010. Emerg Infect Dis \n                           19, 1859\u20131862, https:\/\/doi.org\/10.3201\/eid1911.121548 (2013).","journal-title":". EmergInfect Dis"},{"key":"16474_CR11","doi-asserted-by":"publisher","first-page":"1428","DOI":"10.3201\/eid1909.130201","volume":"19","author":"TA Kelly","year":"2013","unstructured":"Kelly, T. A. et al. Underreporting of viral encephalitis and viral meningitis, Ireland, 2005\u20132008. Emerg Infect Dis \n                           19, 1428\u20131436, https:\/\/doi.org\/10.3201\/eid1909.130201 (2013).","journal-title":"Emerg Infect Dis"},{"key":"16474_CR12","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/S1473-3099(10)70222-X","volume":"10","author":"J Granerod","year":"2010","unstructured":"Granerod, J. et al. Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study. Lancet Infect Dis \n                           10, 835\u2013844, https:\/\/doi.org\/10.1016\/S1473-3099(10)70222-X (2010).","journal-title":"Lancet Infect Dis"},{"key":"16474_CR13","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.1086\/509330","volume":"43","author":"CA Glaser","year":"2006","unstructured":"Glaser, C. A. et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Inefct Dis \n                           43, 1565\u20131577, https:\/\/doi.org\/10.1086\/509330 (2006).","journal-title":"Clin Inefct Dis"},{"key":"16474_CR14","doi-asserted-by":"publisher","first-page":"3576","DOI":"10.1128\/JCM.00862-11","volume":"49","author":"HE Ambrose","year":"2011","unstructured":"Ambrose, H. E. et al. Diagnostic strategy used to establish etiologies of encephalitis in a prospective cohort of patients in England. J Clin Microbiol \n                           49, 3576\u20133583, https:\/\/doi.org\/10.1128\/JCM.00862-11 (2011).","journal-title":"JClin Microbiol"},{"key":"16474_CR15","doi-asserted-by":"publisher","unstructured":"Debiasi, R. L. & Tyler, K. L. Molecular methods for diagnosis of viral encephalitis. Clin. Microbiol Rev \n                           17, 903\u2013925, table of contents, https:\/\/doi.org\/10.1128\/CMR.17.4.903-925.2004 (2004).","DOI":"10.1128\/CMR.17.4.903-925.2004"},{"key":"16474_CR16","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1177\/0883073813513330","volume":"29","author":"M Adenot","year":"2014","unstructured":"Adenot, M. et al. Clinical presentation of severe viral encephalitis with known causative agents in children: a retrospective study on 16 patients hospitalized in a pediatric intensive care unit (2008-2011). J Child Neurol \n                           29, 1508\u20131518, https:\/\/doi.org\/10.1177\/0883073813513330 (2014).","journal-title":"J Child Neurol"},{"key":"16474_CR17","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1093\/cid\/cir1038","volume":"54","author":"MS Gable","year":"2012","unstructured":"Gable, M. S., Sheriff, H., Dalmau, J., Tilley, D. H. & Glaser, C. A. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis \n                           54, 899\u2013904, https:\/\/doi.org\/10.1093\/cid\/cir1038 (2012).","journal-title":"Clin Infect Dis"},{"key":"16474_CR18","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jns.2011.01.012","volume":"303","author":"CN Soares","year":"2011","unstructured":"Soares, C. N. et al. Review of the etiologies of viral meningitis and encephalitis in a dengue endemic region. J Neurol Sci \n                           303, 75\u201379, https:\/\/doi.org\/10.1016\/j.jns.2011.01.012 (2011).","journal-title":"J Neuro lSci"},{"key":"16474_CR19","doi-asserted-by":"publisher","first-page":"e153","DOI":"10.1016\/S2214-109X(13)70060-3","volume":"1","author":"M Mallewa","year":"2013","unstructured":"Mallewa, M. et al. Viral CNS infections in children from a malaria-endemic area of Malawi: a prospective cohort study. Lancet Glob Health \n                           1, e153\u2013160, https:\/\/doi.org\/10.1016\/S2214-109X(13)70060-3 (2013).","journal-title":"LancetGlob Health"},{"key":"16474_CR20","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.jcv.2014.02.001","volume":"60","author":"M Venter","year":"2014","unstructured":"Venter, M. et al. Macroarray assay for differential diagnosis of meningoencephalitis in southernAfrica. J Clin Virol \n                           60, 50\u201356, https:\/\/doi.org\/10.1016\/j.jcv.2014.02.001 (2014).","journal-title":"J Clin Virol"},{"key":"16474_CR21","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1093\/cid\/ciu912","volume":"60","author":"SN Naccache","year":"2015","unstructured":"Naccache, S. N. et al. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing. Clin Infect Dis \n                           60, 919\u2013923, https:\/\/doi.org\/10.1093\/cid\/ciu912 (2015).","journal-title":"Clin Infect Dis"},{"key":"16474_CR22","doi-asserted-by":"publisher","first-page":"e93993","DOI":"10.1371\/journal.pone.0093993","volume":"9","author":"BK Chan","year":"2014","unstructured":"Chan, B. K., Wilson, T., Fischer, K. F. & Kriesel, J. D. Deep sequencing to identify the causes of viral encephalitis. PloS One \n                           9, e93993, https:\/\/doi.org\/10.1371\/journal.pone.0093993 (2014).","journal-title":"PloS One"},{"key":"16474_CR23","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.cyto.2015.10.001","volume":"77","author":"K Kothur","year":"2016","unstructured":"Kothur, K., Wienholt, L., Brilot, F. & Dale, R. C. CSF cytokines\/chemokines as biomarkers in neuroinflammatory CNS disorders: A systematic review. Cytokine \n                           77, 227\u2013237, https:\/\/doi.org\/10.1016\/j.cyto.2015.10.001 (2016).","journal-title":"Cytokine"},{"key":"16474_CR24","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1086\/648420","volume":"49","author":"C Glaser","year":"2009","unstructured":"Glaser, C. & Bloch, K. C. Encephalitis: why we need to keep pushing the envelope. ClinInfect Dis \n                           49, 1848\u20131850, https:\/\/doi.org\/10.1086\/648420 (2009).","journal-title":"ClinInfect Dis"},{"key":"16474_CR25","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.pneurobio.2011.09.003","volume":"95","author":"A Helmy","year":"2011","unstructured":"Helmy, A., De Simoni, M. G., Guilfoyle, M. R., Carpenter, K. L. & Hutchinson, P. J. Cytokines and innate inflammation in the pathogenesis of human traumatic brain injury. Prog. Neurobiol \n                           95, 352\u2013372, https:\/\/doi.org\/10.1016\/j.pneurobio.2011.09.003 (2011).","journal-title":"Prog. Neurobiol"},{"key":"16474_CR26","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1513\/pats.201102-018MW","volume":"8","author":"CG Lee","year":"2011","unstructured":"Lee, C. G. et al. Studies of vascular endothelial growth factor in asthma and chronic obstructive pulmonary disease. Proc. Am. Thor Soc \n                           8, 512\u2013515, https:\/\/doi.org\/10.1513\/pats.201102-018MW (2011).","journal-title":"Proc. Am. Thor Soc"},{"key":"16474_CR27","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1002\/jmv.24140","volume":"87","author":"M Palus","year":"2015","unstructured":"Palus, M. et al. Analysis of serum levels of cytokines, chemokines, growth factors, and monoamine neurotransmitters in patients with tick-borne encephalitis: identification of novel inflammatory markers with implications for pathogenesis. J Med Virol \n                           87, 885\u2013892, https:\/\/doi.org\/10.1002\/jmv.24140 (2015).","journal-title":"J Med Virol"},{"key":"16474_CR28","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1086\/317643","volume":"183","author":"M van der Flier","year":"2001","unstructured":"van der Flier, M. et al. Vascular endothelial growth factor in bacterial meningitis: detection in cerebrospinal fluid and localization in postmortem brain. J Infect Dis \n                           183, 149\u2013153, https:\/\/doi.org\/10.1086\/317643 (2001).","journal-title":"J Infect Dis"},{"key":"16474_CR29","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.jinf.2007.11.004","volume":"56","author":"N Husain","year":"2008","unstructured":"Husain, N., Awasthi, S., Haris, M., Gupta, R. K. & Husain, M. Vascular endothelial growth factor as a marker of disease activity in neurotuberculosis. J Infect \n                           56, 114\u2013119, https:\/\/doi.org\/10.1016\/j.jinf.2007.11.004 (2008).","journal-title":"J Infect"},{"key":"16474_CR30","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.virol.2015.03.011","volume":"482","author":"TG Phan","year":"2015","unstructured":"Phan, T. G. et al. Small circular single stranded DNA viral genomes in unexplained cases of human encephalitis, diarrhea, and in untreated sewage. Virology \n                           482, 98\u2013104, https:\/\/doi.org\/10.1016\/j.virol.2015.03.011 (2015).","journal-title":"Virology"},{"key":"16474_CR31","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1126\/science.1152586","volume":"319","author":"H Feng","year":"2008","unstructured":"Feng, H., Shuda, M., Chang, Y. & Moore, P. S. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science \n                           319, 1096\u20131100, https:\/\/doi.org\/10.1126\/science.1152586 (2008).","journal-title":"Science"},{"key":"16474_CR32","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/j.jcv.2007.09.008","volume":"40","author":"P Norja","year":"2007","unstructured":"Norja, P., Ubillos, I., Templeton, K. & Simmonds, P. No evidence for an association between infections with WU and KI polyomaviruses and respiratory disease. J Clin Virol \n                           40, 307\u2013311, https:\/\/doi.org\/10.1016\/j.jcv.2007.09.008 (2007).","journal-title":"J Clin Virol"},{"key":"16474_CR33","doi-asserted-by":"publisher","first-page":"e1001024","DOI":"10.1371\/journal.ppat.1001024","volume":"6","author":"E van der Meijden","year":"2010","unstructured":"van der Meijden, E. et al. Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Path \n                           6, e1001024, https:\/\/doi.org\/10.1371\/journal.ppat.1001024 (2010).","journal-title":"PLoS Path"},{"key":"16474_CR34","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.3201\/eid1409.080570","volume":"4","author":"JF Drexler","year":"2008","unstructured":"Drexler, J. F. et al. Circulation of 3 lineages of a novel Saffold cardiovirus in humans. Emerg Infect Dis1 \n                           4, 1398\u20131405, https:\/\/doi.org\/10.3201\/eid1409.080570 (2008).","journal-title":"Emerg Infect Dis1"},{"key":"16474_CR35","doi-asserted-by":"publisher","first-page":"3446","DOI":"10.1128\/JCM.01207-08","volume":"46","author":"H Harvala","year":"2008","unstructured":"Harvala, H. et al. Epidemiology and clinical associations of human parechovirus respiratory infections. J Clin Microbiol \n                           46, 3446\u20133453, https:\/\/doi.org\/10.1128\/JCM.01207-08 (2008).","journal-title":"J Clin Microbiol"},{"key":"16474_CR36","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1007\/s00705-011-0995-y","volume":"156","author":"TH Han","year":"2011","unstructured":"Han, T. H., Kim, C. H., Park, S. H., Chung, J. Y. & Hwang, E. S. Detection of human parechoviruses in children with gastroenteritis in South Korea. Arch Virol \n                           156, 1471\u20131475, https:\/\/doi.org\/10.1007\/s00705-011-0995-y (2011).","journal-title":"Arch Virol"},{"key":"16474_CR37","doi-asserted-by":"publisher","first-page":"e37732","DOI":"10.1371\/journal.pone.0037732","volume":"7","author":"X Lv","year":"2012","unstructured":"Lv, X. et al. Isolates of Liao ning virus from wild-caught mosquitoes in the Xinjiang province of China in 2005. PloS One \n                           7, e37732, https:\/\/doi.org\/10.1371\/journal.pone.0037732 (2012).","journal-title":"PloS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16474-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16474-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16474-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T13:57:48Z","timestamp":1671803868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16474-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,23]]},"references-count":37,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["16474"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-16474-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2017,11,23]]},"assertion":[{"value":"4 September 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16181"}}