Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting
| dc.contributor.author | Manyelo, Charles M. | en_ZA |
| dc.contributor.author | Solomons, Regan | en_ZA |
| dc.contributor.author | Snyders, Candice I. | en_ZA |
| dc.contributor.author | Manngo, Portia M. | en_ZA |
| dc.contributor.author | Mutavhatsindi, Hygon | en_ZA |
| dc.contributor.author | Kriel, Belinda | en_ZA |
| dc.contributor.author | Stanley, Kim | en_ZA |
| dc.contributor.author | Walzl, Gerhard | en_ZA |
| dc.contributor.author | Chegou, Novel N. | en_ZA |
| dc.date.accessioned | 2019-07-23T10:18:05Z | |
| dc.date.available | 2019-07-23T10:18:05Z | |
| dc.date.issued | 2019-04 | |
| dc.description | CITATION: 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.description | The original publication is available at https://www.hindawi.com | |
| dc.description | Publication of this article was funded by the Stellenbosch University Open Access Fund | |
| dc.description.abstract | Background. 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.uri | https://www.hindawi.com/journals/mi/2019/7582948/ | |
| dc.description.version | Publisher's version | |
| dc.format.extent | 12 pages | en_ZA |
| dc.identifier.citation | 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.identifier.issn | 1466-1861 (online) | |
| dc.identifier.issn | 0962-9351 (print) | |
| dc.identifier.other | doi:10.1155/2019/7582948 | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/106322 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Hindawi | en_ZA |
| dc.rights.holder | Authors retain copyright | en_ZA |
| dc.subject | Tuberculous meningitis -- Diagnosis | en_ZA |
| dc.subject | Cerebrospinal fluid -- Examination | en_ZA |
| dc.subject | Tuberculosis in children | en_ZA |
| dc.title | Application of cerebrospinal fluid host protein biosignatures in the diagnosis of tuberculous meningitis in children from a high burden setting | en_ZA |
| dc.type | Article | en_ZA |