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. 2018 Jul;12(7):707-716.
doi: 10.2217/bmm-2017-0373. Epub 2018 Jun 1.

Delta-like 1 protein, vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis

Nathan C Bahr  1   2   3 , Ryan Halupnick  1 , Grace Linder  1 , Reuben Kiggundu  2 , Henry W Nabeta  2 , Darlisha A Williams  1   2 , Abdu K Musubire  2 , Bozena M Morawski  1 , Srinand Sreevatsan  4 , David B Meya  1   2 , Joshua Rhein  1   2 , David R Boulware  1
Affiliations

Delta-like 1 protein, vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis

Nathan C Bahr et al. Biomark Med. 2018 Jul.

Abstract

Aim: Tuberculosis meningitis (TBM) diagnosis is difficult, new biomarkers are needed. We evaluated the diagnostic utility of delta-like 1 protein (DLL1), vitamin D binding protein (VDBP) and fetuin.

Methods: Biomarker concentrations were measured by ELISA in cryopreserved cerebrospinal fluid from 139 HIV-infected Ugandans with suspected meningitis. TBM was diagnosed by GeneXpert MTB/Rif or culture. Cohort diagnoses included TBM (n = 22), cryptococcal (n = 71), or aseptic meningitis (n = 16) and no meningitis (n = 30).

Results: DLL1 (cut-off value 1150 pg/ml) provided 32% sensitivity and 98% specificity. Adding fetuin, cryptococcal antigen and IFN-γ resulted in sensitivities of 36, 63 and 76% with specificities of 98, 90 and 92%, respectively. VDBP (cut-off value 2.0 μg/ml) provided 81% sensitivity and 68% specificity while fetuin (cut-off value 2 μg/ml) provided a sensitivity of 86% and specificity of 68%.

Conclusion: CSF DLL1, VDBP and fetuin exhibited fair diagnostic performance for TBM diagnosis.

Keywords: Mycobacterium tuberculosis; TB meningitis; biomarkers.

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Conflict of interest statement

Financial & competing interests disclosure

This research was made possible through support from the Fogarty International Center (R25TW009345), the National Institute of Neurologic Diseases and Stroke (R01NS086312) and the National Institute of Allergy and Infectious Diseases (U01AI089244). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Receiver operator characteristic curve.
The ROC above shows an AUC of 0.789 (95% CI: 0.676–0.902) for DLL1. AUC: Area under the curve.
See this image and copyright information in PMC

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