| Summary: | With an estimated third of all tuberculosis (TB) cases being missed, the need to develop rapid, simple and accurate diagnostic tests is critical. The last five years has seen an unprecedented activity in the development of a range of new tests. However, a major concern is that not all marketed TB tests have been assessed rigorously, particularly in terms of diagnostic accuracy, robustness under operational conditions in the field, and practical usefulness. This dissertation comprises a compilation of diagnostic clinical studies of novel point-of-care tests, namely a chemiresistive "TB breath-analyser"; a lipoarabinomannan (LAM) urine dipstick, and an adaptation of the Xpert®MTB/RIF assay for use on blood. Lastly, there is a modification of the sputum collection device (SCD) to enable specimen processing without the requirement of a biosafety cabinet. The chemiresistive sensor, which detects volatile organic compounds released by Mycobacterium tuberculosis in a patient's breath, demonstrated a high sensitivity (100%) and specificity (92%) for distinguishing patients with active TB from healthy controls. However, sensitivity (74%) and specificity (63%) were lower when the culture-negative participant group was compared to the culture-positive participants. The test shows potential as a useful screening test for TB with further refinement of the sensor technology. The LAM dipstick was shown to be useful in hospitalised HIV-infected patients with CD4 T-cell counts <200 cells/μL reinforcing the data from other studies. Although the blood Xpert®MTB/RIF assay showed some utility in diagnosis of TB in hospitalised patients with very advanced HIV, given the poor sensitivity and specificity, and the requirement for specialised equipment as well as a large volume of blood for testing, it is unlikely that Xpert®MTB/RIF testing on blood will contribute much over other existing diagnostics in resource-limited settings. Finally, the redesigned SCD offers a solution to biosafety concerns with minimal impact on patient acceptability and clinical care.
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