Point-of-care urine test for assessing adherence to isoniazid treatment for tuberculosis

Abstract

To the Editor: Good adherence to treatment for tuberculosis (TB) is essential, both to cure disease and prevent development of drug resistance. Adherence to chemoprophylaxis (preventive therapy) for latent TB infection (LTBI) is particularly poor [1]. Methods for measuring adherence to TB medication include detecting urine colour change due to the presence of rifampicin. However, this effect is short lived, peaking at 2–6 h and is only seen in <50% of patients [2]. Directly observed therapy (DOT) will ensure adherence to antituberculous treatment, but this can be unacceptable and many patients do not tolerate a three times a week regimen. DOT is costly in terms of personnel and is seldom employed in chemoprophylaxis patients [1]. The highly reliable Arkansas method for detecting isoniazid metabolites in urine relies on a laboratory colorimetric assay, involving adding drops of prepared solutions of reagents, including potassium cyanide, to a urine sample [3]. There are obvious risks involved in handling and storing the reagents. IsoScreen (GFC Diagnostics, Bicester, UK) uses the reagents of the Arkansas Method but in an enclosed plastic testing device (SafeTube; GFC Diagnostics), allowing safe and rapid point-of-care testing in clinics and patients’ homes [2]. The urine colour change is apparent within a few seconds but 5 min is allowed to ensure stable colour development. Purple or blue samples are deemed positive, green intermediate and yellow negative. High sensitivities and specificities have been reported, but without a consistent relationship to the timing of the previous dose of isoniazid or measurement of acetylator status [2, 4]. In this prospective study, we analysed the relationship over time of the colour change seen with IsoScreen over 72 h to determine whether different colours could accurately inform when the last dose was taken, …