Development of colorimetric sensor array for diagnosis of tuberculosis through detection of urinary volatile organic compounds

• Published in: Diagnostic microbiology and infectious disease 2018-12, Vol.92 (4), p.299-304
• Main Authors: Sandlund, Johanna, Lim, Sung, Queralto, Nuria, Huang, Richard, Yun, Jaesub, Taba, Brian, Song, Rinn, Odero, Ronald, Ouma, Gregory, Sitati, Ruth, Murithi, Wilfred, Cain, Kevin P., Banaei, Niaz
• Format: Article
• Language: English
• Subjects: Case-Control Studies; Coinfection; Colorimetric sensor array; Colorimetry - methods; Diagnostic performance; Female; HIV Infections; Humans; Interferon-gamma Release Tests; Male; Mycobacterium tuberculosis - isolation & purification; Mycobacterium tuberculosis - metabolism; Reproducibility of Results; Sensitivity and Specificity; Sputum - microbiology; Tuberculosis; Tuberculosis - diagnosis; Tuberculosis - microbiology; Tuberculosis - urine; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - urine; Urine headspace analysis; Volatile organic compounds; Volatile Organic Compounds - urine
• ISSN: 0732-8893; 1879-0070
• DOI: 10.1016/j.diagmicrobio.2018.06.014

Top priorities for tuberculosis control and elimination include a simple, low-cost screening test using sputum and a non-sputum-based test in patients that do not produce sputum. The aim of this study was to evaluate the performance of a colorimetric sensor array (CSA) test, for analysis of volatile organic compounds in urine, in the diagnosis of pulmonary TB. Urine samples were collected from individuals suspected of having pulmonary TB in Western Kenya. Reference methods included MGIT culture and/or Xpert MTB/RIF nucleic acid amplification test on sputa. Fresh urine samples were tested with the CSA, with acid and base and without an additive. The CSA were digitally imaged, and the resulting colorimetric response patterns were used for chemometric analysis. Sensitivity, specificity, and negative (NPV) and positive predictive (PPV) values were determined for HIV-positive and HIV-negative patients. In HIV-negative patients, the highest accuracy was obtained in urine samples pre-treated with a base, yielding a sensitivity, specificity, PPV, and NPV of 78.3% (65/83), 69.2% (54/78), 73.0% (n/89) and 75.0% (n/72). The highest sensitivity of 79.5% was achieved using sensor data from all three test conditions at a specificity of 65.4%. In HIV-positive subjects, the sensor performance was substantially lower with sensitivity, specificity, PPV, and NPV ranging from 48.3% to 62.3%, 54.1% to 74.0%, 55.9% to 64.2%, and 60.6% to 64.9%, respectively. The CSA fingerprint of urine headspace volatiles showed moderate accuracy in diagnosing TB in HIV-negative patients, but the sensor performance dropped substantially in HIV-coinfected patients. Further development of TB-responsive CSA indicators may improve the accuracy of CSA urine assay.