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

Nathan C Bahr; Ryan Halupnick; Grace Linder; Reuben Kiggundu; Henry W. Nabeta; Darlisha A. Williams; Abdu K. Musubire; Bozena M. Morawski; Srinand Sreevatsan; David B. Meya; Joshua R Rhein; David R Boulware

doi:10.2217/bmm-2017-0373

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

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

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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.

Original language	English (US)
Pages (from-to)	707-716
Number of pages	10
Journal	Biomarkers in Medicine
Volume	12
Issue number	7
DOIs	https://doi.org/10.2217/bmm-2017-0373
State	Published - Jul 2018

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Publisher Copyright:
© 2018 2018 Future Medicine Ltd.

Keywords

Mycobacterium tuberculosis
TB meningitis
biomarkers

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161141

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Bahr, N. C., Halupnick, R., Linder, G., Kiggundu, R., Nabeta, H. W., Williams, D. A., Musubire, A. K., Morawski, B. M., Sreevatsan, S., Meya, D. B., Rhein, J. R., & Boulware, D. R. (2018). Delta-like 1 protein, Vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis. Biomarkers in Medicine, 12(7), 707-716. https://doi.org/10.2217/bmm-2017-0373

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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.",

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author = "Bahr, {Nathan C} and Ryan Halupnick and Grace Linder and Reuben Kiggundu and Nabeta, {Henry W.} and Williams, {Darlisha A.} and Musubire, {Abdu K.} and Morawski, {Bozena M.} and Srinand Sreevatsan and Meya, {David B.} and Rhein, {Joshua R} and Boulware, {David R}",

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AU - Nabeta, Henry W.

AU - Williams, Darlisha A.

AU - Musubire, Abdu K.

AU - Morawski, Bozena M.

AU - Sreevatsan, Srinand

AU - Meya, David B.

AU - Rhein, Joshua R

AU - Boulware, David R

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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