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Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting

dc.contributor.authorManyelo, Charles M.en_ZA
dc.contributor.authorSolomons, Regan S.en_ZA
dc.contributor.authorSnyders, Candice I.en_ZA
dc.contributor.authorManngo, Portia M.en_ZA
dc.contributor.authorMutavhatsindi, Hygonen_ZA
dc.contributor.authorKriel, Belindaen_ZA
dc.contributor.authorStanley, Kimen_ZA
dc.contributor.authorWalzl, Gerharden_ZA
dc.contributor.authorChegou, Novel N.en_ZA
dc.date.accessioned2019-07-23T10:18:05Z
dc.date.available2019-07-23T10:18:05Z
dc.date.issued2019-04
dc.identifier.citationManyelo, C. M., et al. 2019. Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting. Mediators of Inflammation, 2019 (Article ID 7582948), doi:10.1155/2019/7582948
dc.identifier.issn1466-1861 (online)
dc.identifier.issn0962-9351 (print)
dc.identifier.otherdoi:10.1155/2019/7582948
dc.identifier.urihttp://hdl.handle.net/10019.1/106322
dc.descriptionCITATION: Manyelo, C. M., et al. 2019. Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting. Mediators of Inflammation, 2019 (Article ID 7582948), doi:10.1155/2019/7582948.
dc.descriptionThe original publication is available at https://www.hindawi.com
dc.descriptionPublication of this article was funded by the Stellenbosch University Open Access Fund
dc.description.abstractBackground. The diagnosis of tuberculous meningitis (TBM) especially in children is challenging. New tests are urgently needed for the diagnosis of the disease, especially in resource-limited settings. Methods. We collected cerebrospinal fluid (CSF) samples from children presenting with symptoms requiring investigation for meningitis at a tertiary hospital in Cape Town, South Africa. Children were later classified as TBM or no TBM using published case definitions. Using a multiplex platform, we investigated the concentrations of biomarkers comprising a previously established 3-marker biosignature (VEGF, IL-13, and LL-37) and other potentially useful host biomarkers as diagnostic candidates for TBM. Findings. Out of 47 children, age, 3 months to 13 years, 23 were diagnosed with TBM and six (16%) were HIV-infected. We validated the previously identified CSF biosignature (sensitivity of 95.7% (95% CI, 79.0-99.2%) and specificity of 37.5% (95% CI, 21.2-57.3%)). However, substitution of IL-13 and LL-37 with IFN-γ and MPO, respectively, resulted in improved accuracy (area under the ROC curve (AUC) = 0 97, 95% CI, 0.92-1.00, up to 91.3% (21/23) sensitivity and up to 100% (24/24) specificity). An alternative four-marker biosignature (sICAM-1, MPO, CXCL8, and IFN-γ) also showed potential, with an AUC of 0.97. Conclusion. We validated a previously identified CSF biosignature and showed that refinement of this biosignature by incorporation of other biomarkers diagnosed TBM with high accuracy. Incorporation of these biomarkers into a point-of-care or bedside diagnostic test platform may result in the improved management of TBM in children.en_ZA
dc.description.urihttps://www.hindawi.com/journals/mi/2019/7582948/
dc.format.extent12 pages
dc.language.isoen_ZAen_ZA
dc.publisherHindawi
dc.subjectTuberculous meningitisen_ZA
dc.titleApplication of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden settingen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's version
dc.rights.holderAuthors retain copyright


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