Objective measurement of isoniazid levels: practical approach for monitoring tuberculosis drug treatment adherence

Abstract

Drug treatment adherence is one of the biggest issues in tuberculosis (TB) treatment. Including DOTS (Directly Observed Treatment, Short-course) program, many programs for TB cases have yielded marginal success and the new drug resistance varieties of TB persist. During the 1960s, researchers have projected naphthoquinone-mercuric chloride (N-M) test as the single most way to objectively track the presence of isoniazid (INH) in urine and hence treatment adherence. INH is metabolised by cytochrome P450s and usually cleared from body within 8 h. Hence, the typical INH levels in biological fluids are within 1-5 μg/ml. The N-M test practically works at 10-50 μg/ml and the authors developed the sodium polyacrylate (SPA) as a solid surface to improve detection limit of INH by 6-10 fold. The modification involves absorbing the reagents of N-M test on the SPA surface and lyophilised material is directly used for diagnosis. The dry beads can detect 1-2 μg/ml of INH in saliva. The test performed with spiked as well as clinical samples and the results have good correlation. This new test has a realistic chance of tracking the TB treatment adherence remotely and in that direction a system was projected for implementation.