{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T20:28:25Z","timestamp":1780086505486,"version":"3.54.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T00:00:00Z","timestamp":1482451200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,12,23]],"date-time":"2016-12-23T00:00:00Z","timestamp":1482451200000},"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>As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for <jats:italic>Streptococcus pneumoniae, Neisseria meningitidis<\/jats:italic>, and <jats:italic>Haemophilus influenzae<\/jats:italic>. Of 266 samples tested, pathogens were identified in 47 (17.7%). <jats:italic>S. pneumoniae<\/jats:italic> was the most common pathogen detected (n\u2009=\u200917) followed by <jats:italic>N. meningitidis<\/jats:italic> (n\u2009=\u200913). The use of qPCR significantly increased detection of IB-VPD pathogens (P\u2009=\u20090.0001): of 35 samples that were qPCR positive for <jats:italic>S. pneumoniae, N. meningitidis<\/jats:italic>, and <jats:italic>H. influenzae<\/jats:italic>, only 10 were culture positive. This was particularly relevant for <jats:italic>N. meningitidis<\/jats:italic>, as only 1\/13 cases was culture positive. Molecular serotyping by microarray was used to determine pneumococcal serotypes from 9 of 16 (56%) of samples using DNA directly extracted from CSF specimens. Results indicate that qPCR significantly increases detection of <jats:italic>S. pneumoniae, N. meningitidis<\/jats:italic>, and <jats:italic>H. influenzae<\/jats:italic> in CSF, and that application of molecular diagnostics is a feasible way to enhance local and global surveillance for IB-VPD.<\/jats:p>","DOI":"10.1038\/srep39784","type":"journal-article","created":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T21:33:58Z","timestamp":1482615238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji"],"prefix":"10.1038","volume":"6","author":[{"given":"Eileen M.","family":"Dunne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silivia","family":"Mantanitobua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini P.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Reyburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Tuivaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Rafai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisi","family":"Tikoduadua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Porter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Satzke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet E.","family":"Strachan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly K.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylie M.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Jenney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silo","family":"Baro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Kim","family":"Mulholland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Kama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona M.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,23]]},"reference":[{"key":"BFsrep39784_CR1","doi-asserted-by":"publisher","first-page":"2139","DOI":"10.1016\/S0140-6736(03)13693-8","volume":"361","author":"X S\u00e1ez-Llorens","year":"2003","unstructured":"S\u00e1ez-Llorens, X. & McCracken, G. H. Jr. Bacterial meningitis in children. Lancet 361, 2139\u20132148 (2003).","journal-title":"Lancet"},{"key":"BFsrep39784_CR2","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1016\/S0140-6736(12)61187-8","volume":"380","author":"PB McIntyre","year":"2012","unstructured":"McIntyre, P. B., O\u2019Brien, K. L., Greenwood, B. & van de Beek, D. Effect of vaccines on bacterial meningitis worldwide. Lancet 380, 1703\u20131711 (2012).","journal-title":"Lancet"},{"key":"BFsrep39784_CR3","doi-asserted-by":"publisher","first-page":"S410","DOI":"10.1093\/cid\/civ597","volume":"61","author":"C Lingani","year":"2015","unstructured":"Lingani, C. et al. Meningococcal meningitis surveillance in the African meningitis belt, 2004\u20132013. Clin. Infect. Dis. 61, S410\u2013S415 (2015).","journal-title":"Clin. Infect. Dis."},{"key":"BFsrep39784_CR4","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1056\/NEJMoa1401914","volume":"371","author":"A von Gottberg","year":"2014","unstructured":"von Gottberg, A. et al. Effects of vaccination on invasive pneumococcal disease in South Africa. N. Engl. J. Med. 371, 1889\u20131899 (2014).","journal-title":"N. Engl. J. Med."},{"key":"BFsrep39784_CR5","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1128\/CMR.00070-09","volume":"23","author":"MC Brouwer","year":"2010","unstructured":"Brouwer, M. C., Tunkel, A. R. & van de Beek, D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin. Microbiol. Rev. 23, 467\u2013492 (2010).","journal-title":"Clin. Microbiol. Rev."},{"key":"BFsrep39784_CR6","doi-asserted-by":"publisher","first-page":"e0138249","DOI":"10.1371\/journal.pone.0138249","volume":"10","author":"AA Nhantumbo","year":"2015","unstructured":"Nhantumbo, A. A. et al. Frequency of pathogenic paediatric bacterial meningitis in Mozambique: the critical role of multiplex real-time polymerase chain reaction to estimate the burden of disease. PLoS One 10, e0138249; 10.1371\/journal.pone.0138249 (2015).","journal-title":"PLoS One"},{"key":"BFsrep39784_CR7","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1111\/j.1469-0691.2007.01756.x","volume":"13","author":"C Welinder-Olsson","year":"2007","unstructured":"Welinder-Olsson, C. et al. Comparison of broad-range bacterial PCR and culture of cerebrospinal fluid for diagnosis of community-acquired bacterial meningitis. Clin. Microbiol. Infect. 13, 879\u2013886 (2007).","journal-title":"Clin. Microbiol. Infect."},{"key":"BFsrep39784_CR8","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1099\/jmm.0.2008\/000935-0","volume":"57","author":"C Azzari","year":"2008","unstructured":"Azzari, C. et al. Molecular detection methods and serotyping performed directly on clinical samples improve diagnostic sensitivity and reveal increased incidence of invasive disease by Streptococcus pneumoniae in Italian children. J. Med. Microbiol. 57, 1205\u20131212 (2008).","journal-title":"J. Med. Microbiol."},{"key":"BFsrep39784_CR9","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.ijmm.2010.11.004","volume":"301","author":"X Wang","year":"2011","unstructured":"Wang, X. et al. Detection of bacterial pathogens in Mongolia meningitis surveillance with a new qPCR assay to detect Haemophilus influenzae. Int. J. Med. Microbiol. 301, 303\u2013309 (2011).","journal-title":"Int. J. Med. Microbiol."},{"key":"BFsrep39784_CR10","unstructured":"Laboratory methods for the diagnosis of meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, WHO Manual. 2nd edn, (WHO Press, World Health Organization, 2011)."},{"key":"BFsrep39784_CR11","unstructured":"Vandepitte, J. Basic Laboratory Procedures in Clinical Microbiology. 2nd edn, (World Health Organization, 2003)."},{"key":"BFsrep39784_CR12","doi-asserted-by":"crossref","unstructured":"Porter, B. D., Ortika, B. D. & Satzke, C. Capsular Serotyping of Streptococcus pneumoniae by latex agglutination. J Vis Exp. 51747, 10.3791\/51747 (2014).","DOI":"10.3791\/51747"},{"key":"BFsrep39784_CR13","doi-asserted-by":"publisher","first-page":"e1001903","DOI":"10.1371\/journal.pmed.1001903","volume":"12","author":"C Satzke","year":"2015","unstructured":"Satzke, C., Dunne, E. M., Porter, B. D., Klugman, K. P. & Mulholland, E. K. The PneuCarriage Project: a multi-centre comparative study to identify the best serotyping methods for examining pneumococcal carriage in vaccine evaluation studies. PLoS Med 12, e1001903; 10.1371\/journal.pmed.1001903 (2015).","journal-title":"PLoS Med"},{"key":"BFsrep39784_CR14","doi-asserted-by":"publisher","first-page":"e289","DOI":"10.1016\/j.ijid.2011.12.013","volume":"16","author":"VL Biaukula","year":"2012","unstructured":"Biaukula, V. L. et al. Meningitis in children in Fiji: aetiology, epidemiology, and neurological sequelae. Int. J. Infect. Dis. 16, e289\u2013e295 (2012).","journal-title":"Int. J. Infect. Dis."},{"key":"BFsrep39784_CR15","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.3201\/eid1407.070938","volume":"14","author":"C Mehmet","year":"2008","unstructured":"Mehmet, C. et al. A prospective study of aetiology of childhood acute bacterial meningitis, Turkey. Emerg. Infect. Dis. 14, 1089 (2008).","journal-title":"Emerg. Infect. Dis."},{"key":"BFsrep39784_CR16","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1086\/426436","volume":"40","author":"IPd Ch\u00e2telet","year":"2005","unstructured":"Ch\u00e2telet, I. P. d. et al. Bacterial meningitis in Burkina Faso: surveillance using field-based polymerase chain reaction testing. Clin. Infect. Dis. 40, 17\u201325 (2005).","journal-title":"Clin. Infect. Dis."},{"key":"BFsrep39784_CR17","doi-asserted-by":"publisher","first-page":"645","DOI":"10.4103\/0972-2327.120491","volume":"16","author":"SF Mohammadi","year":"2013","unstructured":"Mohammadi, S. F., Patil, A. B., Nadagir, S. D., Nandihal, N. & Lakshminarayana, S. A. Diagnostic value of latex agglutination test in diagnosis of acute bacterial meningitis. Ann. Indian Acad. Neurol. 16, 645\u2013649 (2013).","journal-title":"Ann. Indian Acad. Neurol"},{"key":"BFsrep39784_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2334-13-26","volume":"13","author":"HM Wu","year":"2013","unstructured":"Wu, H. M. et al. Accuracy of qPCR, Gram stain and culture for Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae meningitis diagnosis. BMC Infect. Dis. 13, 1\u201310 (2013).","journal-title":"BMC Infect. Dis."},{"key":"BFsrep39784_CR19","doi-asserted-by":"publisher","first-page":"3346","DOI":"10.1128\/JCM.02631-05","volume":"44","author":"FM Russell","year":"2006","unstructured":"Russell, F. M. et al. As a bacterial culture medium, citrated sheep blood agar is a practical alternative to citrated human blood agar in laboratories of developing countries. J. Clin.l Microbiol. 44, 3346\u20133351 (2006).","journal-title":"J. Clin.l Microbiol"},{"key":"BFsrep39784_CR20","unstructured":"Murray, J. et al.Added value of polymerase chain reaction (PCR) testing in detecting pneumococcus in cerebral spinal fluid of suspect meningitis cases in global sentinel invasive bacterial vaccine preventable disease (IB-VPD) surveillance network. In 10th International Symposium on Pneumococci & Pneumococcal Diseases (Glasgow, UK, 2016)."},{"key":"BFsrep39784_CR21","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1086\/321885","volume":"33","author":"K Tarafdar","year":"2001","unstructured":"Tarafdar, K., Rao, S., Recco, R. A. & Zaman, M. M. Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the cerebrospinal fluid of patients with culture-negative meningitis. Clin. Infect. Dis. 33, 406\u2013408 (2001).","journal-title":"Clin. Infect. Dis."},{"key":"BFsrep39784_CR22","doi-asserted-by":"publisher","first-page":"S49","DOI":"10.1086\/596481","volume":"48","author":"JC Mo\u00efsi","year":"2009","unstructured":"Mo\u00efsi, J. C. et al. Enhanced diagnosis of pneumococcal meningitis with use of the Binax NOW immunochromatographic test of Streptococcus pneumoniae antigen: a multisite study. Clin. Infect. Dis. 48, S49\u2013S56 (2009).","journal-title":"Clin. Infect. Dis."},{"key":"BFsrep39784_CR23","doi-asserted-by":"publisher","first-page":"e3576","DOI":"10.1371\/journal.pone.0003576","volume":"3","author":"SK Saha","year":"2008","unstructured":"Saha, S. K. et al. Identification of serotype in culture negative pneumococcal meningitis using sequential multiplex PCR: implication for surveillance and vaccine design. PLoS One 3, e3576, 10.1371\/journal.pone.0003576 (2008).","journal-title":"PLoS One"},{"key":"BFsrep39784_CR24","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1186\/s12879-015-1198-z","volume":"15","author":"S Tempia","year":"2015","unstructured":"Tempia, S. et al. Assessing the impact of pneumococcal conjugate vaccines on invasive pneumococcal disease using polymerase chain reaction-based surveillance: an experience from South Africa. BMC Infect. Dis. 15, 450 (2015).","journal-title":"BMC Infect. Dis."},{"key":"BFsrep39784_CR25","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1001\/jama.297.16.1784","volume":"297","author":"RJ Singleton","year":"2007","unstructured":"Singleton, R. J., Hennessy, T. W., Bulkow, L. R. et al. Invasive pneumococcal disease caused by nonvaccine serotypes among Alaska Native children with high levels of 7-valent pneumococcal conjugate vaccine coverage. JAMA 297, 1784\u20131792 (2007).","journal-title":"JAMA"},{"key":"BFsrep39784_CR26","doi-asserted-by":"publisher","first-page":"7100","DOI":"10.1016\/j.vaccine.2011.06.120","volume":"29","author":"R Arnold","year":"2011","unstructured":"Arnold, R., Galloway, Y., McNicholas, A. & O\u2019Hallahan, J. Effectiveness of a vaccination programme for an epidemic of meningococcal B in New Zealand. Vaccine 29, 7100\u20137106 (2011).","journal-title":"Vaccine"},{"key":"BFsrep39784_CR27","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1093\/ije\/dyn228","volume":"38","author":"Y Galloway","year":"2009","unstructured":"Galloway, Y., Stehr-Green, P., McNicholas, A. & O\u2019Hallahan, J. Use of an observational cohort study to estimate the effectiveness of the New Zealand group B meningococcal vaccine in children aged under 5 years. Int. J. Epidemiol. 38, 413\u2013418 (2009).","journal-title":"Int. J. Epidemiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep39784.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39784","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep39784.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T07:19:33Z","timestamp":1672903173000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep39784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12,23]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep39784"],"URL":"https:\/\/doi.org\/10.1038\/srep39784","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,23]]},"assertion":[{"value":"28 September 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"39784"}}