Browsing by Author "Manngo, Makhadzi Portia"

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    Evaluation of the potential of Mycobacterium tuberculosis antigen-specific host biomarkers detected in QuantiFERON® TB GOLD Plus supernatants in the diagnosis of TB disease
    (Stellenbosch : Stellenbosch University, 2018-12) Manngo, Makhadzi Portia; Chegou, Novel N.; Gutschmidt, Andrea; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: BACKGROUND The diagnosis of tuberculosis (TB) disease remains a challenge. This is mainly due to limitations with the current TB diagnostic tests including unavailability of rapid pointof-care tests. New TB diagnostic tests are therefore urgently needed. The QuantiFERON-TB® Gold (QFT) Plus test is a recently introduced test for the diagnosis of M. tb infection, and disease in some patient groups. As this is a relatively new test which is currently in use worldwide, it is important that its performance be evaluated, especially in high TB burden settings. Furthermore, it is not known whether measurement of host markers other than Interferon-gamma in culture supernatants of individuals with active TB or other respiratory diseases (ORD), has potential in the diagnosis of TB disease. OBJECTIVES 1) To evaluate the usefulness of the QFT Plus test in the diagnosis of TB disease, and assess the utility of the test, when used in combination with symptoms, as a tool for diagnosis of TB disease in people suspected of having active TB in a high burden setting. 2) To evaluate alternative host biomarkers detected in QFT Plus supernatants, other than IFN-γ as biosignatures for the diagnosis of active TB METHODS We recruited 120 participants presenting at a primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease. These participants formed part of a larger ongoing biomarker project known as the ‘ScreenTB’ study. Participants were later classified as TB or ORD based on the results of clinical and laboratory tests. After performing the standard QFT Plus test in study participants, the concentrations of 37 host biomarkers were evaluated in culture supernatants using a multiplex immunoassay. RESULTS Out of 120 individuals included in the study, 35 (29.2%) were diagnosed with active TB and were culture positive. The QFT Plus test diagnosed TB disease in all study participants with sensitivity and specificity >70%. A combination of symptoms including cough, fever and weight loss diagnosed TB disease with sensitivity and specificity >70% with an area under the receiver operator characteristics curve of 0.81. Multiple host biomarkers detected in the unstimulated and antigen-stimulated QFT Plus tubes showed potential as diagnostic markers for TB. Individual markers which diagnosed TB disease with sensitivities and specificities >60% included ITAC-1, IL-3, I-309, MIG, and EGF, P-selectin. Combinations between host biomarkers showed potential in the diagnosis of TB disease with a six-marker biosignature derived from unstimulated supernatants (APO-CII, ITAC-1, MIG, MCP-2, I-309, and NCAM-1) diagnosing TB disease with a sensitivity and specificity >78%, a four-marker TB1 and TB2 antigenspecific biosignature (TNFα, LIGHT, MIG and P-selectin ) which diagnosed TB disease with sensitivity and specificity >73%, after leave-one-out cross validation. CONCLUSION The sensitivity of the QFT Plus test for active TB was inferior to the published >80% mentioned in the package insert by the manufacturer. Host biomarkers detected in QFT Plus supernatants showed potential in the diagnosis of active TB disease. Further validation studies are needed before such markers may be considered as candidate biomarkers for a blood-based diagnostic test for active TB.