Evaluation of Nitrate Reductase Assay For Rapid Detection of Drug Resistant Tuberculosis

Emergence of multidrug-resistant tuberculosis (MDR-TB) urgently demands for simple, rapid and inexpensive methods of its detection for the effective treatment of drug resistant tuberculosis, particularly in low-income countries. This prospective study was carried out at National Tuberculosis Reference Laboratory and South Asian Association of Regional Cooperation (SAARC) Tuberculosis and HIV/AIDS Centre, Thimi, Bhaktapur, Nepal, from November 2009 to May 2010 to evaluate nitrate reductase assay (NRA) efficacy for rapid determination of streptomycin, isoniazid, rifampicin and ethambutol susceptibility of Mycobacterium tuberculosis strains. A total of 113 clinical isolates of M. tuberculosis were tested for four first line antitubercular drugs by nitrate reductase assay and were compared with standard proportion method. Results were available in 7-14 days by NRA as compared to proportion method which generally takes 4-6 weeks. The sensitivity and specificity of NRA were 98.1% and 100% for isoniazid, 95.1% and 98.6% for rifampicin, 91.4% and 94.9% for streptomycin, and 78.6% and 97.9% for ethambutol respectively. Agreement between NRA and proportion method were 99.1%, 97.3%, 93.8%, 95.6% for isoniazid, rifampicin, streptomycin and ethambutol, respectively. NRA is easier, inexpensive and reliable method for susceptibility testing of Mycobacterum tuberculosis for isoniazid and rifampicin, the two most important drugs for the treatment of tuberculosis. The reduction in susceptibility testing time, and higher sensitivity and specificity of NRA method is of fundamental importance in detecting MDR-TB. Key words: Drug susceptibility, MDR-TB, NRA, proportion method

PD64 Diagnostic Accuracy Of The Nitrate Reductase Assay Technique

Introduction:The conventional drug sensitivity test is traditionally used in Brazil to diagnose drug-resistant tuberculosis. However, the test can take up to 60 days to return a diagnosis, which is considered too long for certain vulnerable populations. Therefore, this study analyzed the available scientific evidence on the accuracy and time to diagnosis of the nitrate reductase assay for diagnosing resistant tuberculosis, compared with the conventional drug sensitivity test.Methods:We searched MEDLINE, Embase, and The Cochrane Library for systematic reviews with meta-analyses. The articles were screened by title and abstract. The full-texts of potentially relevant articles were then screened according to the inclusion criteria.Results:Three systematic reviews with meta-analyses were selected that compared the nitrate reductase assay with the conventional drug sensitivity test. The accuracy of the nitrate reductase assay was satisfactory in most of the results when compared with the sensitivity test, except for one study that showed low sensitivity for the detection of streptomycin resistance. In addition, the nitrate reductase assay had a shorter time to diagnosis than the drug sensitivity test.Conclusions:The results of this study reinforce the idea that the nitrate reductase assay may diagnose drug-resistant tuberculosis earlier than the conventional drug sensitivity test and be a helpful strategy for controlling the disease, especially in vulnerable populations that are more likely to be affected by tuberculosis. For a broader analysis of the benefit of the assay, it is suggested that studies investigate the impact of the shorter time to diagnosis on morbidity and mortality in patients with drug-resistant tuberculosis. In addition, economic analyses comparing the nitrate reductase assay with the sensitivity test are recommended to evaluate the cost-benefit ratio.