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

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

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

Bibliographical note

Funding Information:
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.

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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10.2217/bmm-2017-0373

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

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",

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}",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2018 2018 Future Medicine Ltd.",

year = "2018",

month = jul,

doi = "10.2217/bmm-2017-0373",

language = "English (US)",

volume = "12",

pages = "707--716",

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T1 - Delta-like 1 protein, Vitamin D binding protein and fetuin for detection of Mycobacterium tuberculosis meningitis

AU - Bahr, Nathan C

AU - Halupnick, Ryan

AU - Linder, Grace

AU - Kiggundu, Reuben

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

N1 - Funding Information: 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. Publisher Copyright: © 2018 2018 Future Medicine Ltd.

PY - 2018/7

Y1 - 2018/7

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.

KW - Mycobacterium tuberculosis

KW - TB meningitis

KW - biomarkers

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JO - Biomarkers in Medicine

JF - Biomarkers in Medicine

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ER -

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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