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Title: Synthetic lipid antigens for the detection of tuberculosis via ELISA and novel point-of-care flow-through assay
Author: Hacking, Joanne
ISNI:       0000 0004 9358 6599
Awarding Body: Bangor University
Current Institution: Bangor University
Date of Award: 2020
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To end Tuberculosis, point-of-care diagnostic tests accessible by all isolated communities worldwide are required. Using ELISA platform, this study evaluates the use of synthetic lipidsas antigens in diagnostic testsfor the detection of TB (pulmonary, extra-pulmonary, latent TB infection) in patient sera and plasma samples, with and without HIV. Taking the most promising synthetic lipid antigen forwards, a point-of-care flow through assay is developed for the detection of pulmonary TB, with a smartphone application. Using ELISA and the point-of-care flow through assay, the role of synthetic lipid antigens for the detection of Buruli Ulcer is evaluated, with promising results (sensitivity 63%, specificity 80%for ELISA).ELISA with a single synthetic cordfactor (alpha, keto or methoxytrehalose dimycolate) antigen can detect pulmonary TB from non-TB samples from an endemic population with and without HIV. In terms of detection of disease state, synthetic keto TDM antigen can distinguish pulmonary TB from latent TB infection using the IgG antibody response in both ELISA (sensitivity 90%, specificity 80%) and the flow through assay (sensitivity 63%, specificity 90%), with sera or plasma samples. The simple 10 minute flow through assay for less than $10 per test with almost equivalent performance to the laboratory-restricted 3 hour ELISA has reached a new milestone in the development of point-of-care diagnostic tests using synthetic lipid antigens, and the smartphone application opens up the possibility for monitoring of TB patients in isolated communities. Although the performance of ELISA and the Flow Through Assay is not as strong as the leading TB diagnostic Xpert; itis envisaged that with further optimisation the novelflow through assay using synthetic lipid antigens will meetthe World Health Organisation requirements for a point-of-care sensorand makeTB diagnostic testing more accessible to isolated communities most in need.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Tuberculosis ; Diagnosis ; TDM ; lipid ; cordfactor ; Buruli Ulcer ; point-of-care