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.The original publication is available at https://www.hindawi.comPublication of this article was funded by the Stellenbosch University Open Access FundBackground. 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.https://www.hindawi.com/journals/mi/2019/7582948/Publisher's versio
