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1703. Delta-like 1 ligand (DLL) measurement in cerebrospinal fluid for
detection of Mycobacterium tuberculosis meningitis
Nathan Bahr, MD1,2,3; Grace Linder2; Ryan Halupnick2; Reuben Kiggundu MBChB3;
Henry Nabeta, MBChB3; Darlisha Williams, MPH2; David Meya, MMed2,3;
Joshua Rhein, MD1,2,3; David Boulware, MD, MPH1,2;
1
Infectious Disease and
International Medicine, University of Minnesota, Minneapolis, MN;
2
Center for
Infectious Diseases and Microbiology Translational Research, University of Minnesota,
Minneapolis, MN;
3
Infectious Disease Institute,Makerere University, Kampala, Uganda
Session: 208. Mycobacterial Infections: Extrapulmonary
Saturday, October 11, 2014: 12:30 PM
Background.Tuberculosis meningitis (TBM) diagnosis is notoriously difficult,
new biomarkers are needed to allow for improved diagnostic accuracy. We evaluated
the diagnostic utility of a novel biomarker, delta-like ligand 1 (DLL1), a Notch ligand,
which selectively drives antigen-specific CD4 T helper1 cell responses. DLL1 polymor-
phisms increase susceptibility to other intraceullar (Th1) organisms (e.g.,
leishmaniasis).
Methods.CSF DLL1 concentrations were measured by ELISA in 116 patients with
suspected meningitis, of which 18 patients had TBM, 65 patients cryptococcal
meningitis (CM), and 33 patients testednegativeforbothCMandTBM(termed
“other”). TBM was diagnosed either by GeneXpert MTB/Rif assay (Cepheid, Sunny-
vale, CA) or Bactec MGIT culture. We evaluated the diagnostic performance of DLL1
for TBM.
Results.Patient characteristics were similar at diagnosis except for CSF protein
and CSF WBC count. Protein was higher in TBM patients than ‘other’men ingitis,
and CSF WBC count, was higher in TBM than in non-TBM meningitis. Mean
DLL1 CSF concentrations were significantly higher in patients with TBM (1293 pg/
mL; 95%CI, 602-1985 pg/mL) than CM (447 pg/mL; 95%CI, 398-495pg/mL) or
other meningitis (534 pg/mL; 95%CI, 290-669pg/mL). A cutoff of >600pg/mL in
CSF for TBM had 72% sensitivity, 77% specificity, 36% positive predictive value
(PPV), and 94% negative predictive value (NPV) 94% (AUC = 0.794). As the DLL1
level increased, the likelihood of TBM increased with specificity of 92% and PPV of
56% above >800pg/mL.
Conclusion.CSF DLL1 exhibited good diagnostic performance, and may have a
role as a low cost adjunctive diagnostic tool for TBM. Misclassification bias (of non-
detection of TBM classified as ‘other’) hampers diagnostic studies, and larger studies
are required in the future.
Disclosures. All authors: No reported disclosures.
Poster Abstracts •OFID 2014:1 (Suppl 1) •S427