Isoniazid and acetylisoniazid urine concentrations as a maker of adherence to isoniazid preventative therapy in children

Master Thesis

2013

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University of Cape Town

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The World Health Organization recommends the use of isoniazid preventive therapy to reduce the incidence of tuberculosis disease in populations at risk for developing the disease. Adherence to isoniazid preventive therapy is needful for efficacy. A urine assay known as the Arkansas test is widely used to monitor the ingestion of isoniazid. However, this test is limited by a drop in sensitivity with increasing time post isoniazid dose. Furthermore, results from the test can be affected by observer variation in colour changes, concomitant medications, urinary dilution, and presence of other substances in urine. Moreover, the Arkansas test results have not been evaluated against objective measurement of isoniazid and acetylisoniazid urine concentrations. This study seeks to measure the urine concentrations of isoniazid and acetylisoniazid at different time points after a dose in children, in order to establish reference ranges for liquid chromatography tandem mass spectrometry measurements of urine isoniazid and acetylisoniazid, as well as the Arkansas method. The reference ranges would provide a standard which can be used to estimate the probability of adherence to prior doses.
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