101. A Novel Urinary Biomarker of Tuberculosis and Response to Chemotherapy
Session: Oral Abstract Session: Diagnostics: Typing/Sequencing
Thursday, October 8, 2015: 11:00 AM
Room: 7--AB
Background: Tuberculosis (TB) is the leading bacterial cause of death worldwide. However, point of care diagnostic and prognostic tests remain major areas of unmet medical need.

Methods: We conducted a prospective case control study to identify urinary diagnostic biomarkers of TB. Participants were enrolled at the GHESKIO center in Port-au-Prince Haiti from Sept 2011 to March 2012. TB cases were defined by medical history, physical exam, chest radiography, sputum smear for acid-fast bacilli (AFB) and M. tuberculosis culture. Healthy controls were matched by age +/- 5 years, sex and HIV status. Clean-catch urine samples were collected at the time of enrollment from all study participants, which for cases occurred prior to initiation of therapy. Additional urine samples were collected from a subset of cases at several time points during the first 3 months of anti-tuberculosis therapy.  Samples were analyzed by high performance liquid chromatography-coupled time of flight mass spectrometry.  Cases and controls were compared by cross-validation, separating the data set into discovery and validation groups and then further divided into randomly selected small subsets for iterative comparative analysis.

Results: Comparing 102 cases with 103 matched controls in aggregate, we identified 769 compounds as significantly different (p value <0.05). Repeated 20 vs 20 random subset cross-validation analysis revealed one compound, with a mass of 490 (referred to as 490), as significantly different across all data sets. The mean abundance of 490 was significantly higher in patients with active pulmonary TB when compared to matched controls (54,896 counts vs 7,545 counts, p. value 0.0001). In an overall comparison of patients with pulmonary TB and those without, the receiver-operator-characteristic curve for 490 had an area under the curve of 91.1%. The abundance of 490 was also found to decrease over time, following initiation of first line chemo therapy (mean pretreatment abundance 75,913 counts, mean abundance after day 60 of treatment 18,148 counts).

Conclusion: 490 is a urinary biomarker with potential as a dual diagnostic and prognostic marker of active pulmonary TB and response to chemotherapy.

Flonza Isa, MD1, Sean Collins, MD2, Diessy Decome, MD3, Nancy Dorvil, MD3, Patrice Joseph, MD3, Lauren Smith, BS4, Stephen Salerno, -5, Martin Wells, PhD6, Steven Fischer, MS7, Jean William Pape, MD8, Warren Johnson, MD9, Daniel Fitzgerald, MD10 and Kyu Rhee, MD, PhD11, (1)Medicine, NYP/Weill cornell, New York, NY, (2)Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA, (3)GHESKIO, Port-au-Prince, Haiti, (4)Mayo Medical Scheel, Rochester, MN, (5)Cornell, Ithica, NY, (6)Cornell University, Ithica, NY, (7)Agilent Technologies, Santa Clara, CA, (8)GHESKIO, New York, NY, (9)Weill Cornell Medical Center, New York, NY, (10)Weill School of Medicine, New York, NY, (11)Weill Cornell Medical College, New York, NY

Disclosures:

F. Isa, None

S. Collins, None

D. Decome, None

N. Dorvil, None

P. Joseph, None

L. Smith, None

S. Salerno, None

M. Wells, None

S. Fischer, Agilent Technologies: Employee and Investigator , Salary

J. W. Pape, None

W. Johnson, None

D. Fitzgerald, None

K. Rhee, None

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