Diagnostic accuracy of nucleic acid amplification tests in urine for pulmonary tuberculosis: A meta-analysis

Abstract

OBJECTIVE-To determine the diagnostic accuracy of tuberculosis (TB) nucleic acid amplification tests (NAATs) in urine samples for individuals with active pulmonary tuberculosis (PTB).DESIGN-Systematic review and meta-analysis. Electronic databases and reference lists were searched without age or setting restrictions up to May 2015. Eligible articles examined Mycobacterium tuberculosis NAATs in urine samples for PTB diagnosis in patients with sputum culture as the reference standard, and reported sufficient data to separately calculate sensitivity or specificity.RESULTS-Eight studies, including 1212 participants from seven countries with a mean age ranging from 28 to 48 years, were included. Polymerase chain reaction (PCR) with insertion sequence (IS) 6110, rpoB or cfp32/hf6 as gene targets was used for NAATs. The pooled sensitivity and specificity was respectively 0.55 (95%CI 0.36-0.72) and 0.94 (95%CI 0.78-0.99), with slightly higher sensitivity in human immunodeficiency virus positive individuals, at 0.59 (95%CI 0.20-0.89). Sensitivity was higher in sputum microscopy-positive than -negative individuals. Storage temperatures below −70°C, centrifuge speed <5000 rpm and IS6110 increased sensitivity on meta-regression.Correspondence to: Diana Marangu, Department of Paediatrics and Child Health, University of Nairobi, P O Box 19676 -0202, Nairobi, Kenya. marangud@gmail.com. Conflicts of interest: none declared. HHS Public Access KeywordsNAAT; PCR; systematic review; meta-regression In 2013, it was estimated that there were 9 million incident tuberculosis (TB) cases globally, 3.3 million of whom were not diagnosed. 1 Urine nucleic acid amplification tests (NAATs) have potential for use in the diagnosis of pulmonary tuberculosis (PTB), the most common form of TB worldwide. [2][3][4] The relative simplicity of urine collection could be ideal to address diagnostic challenges of active PTB, 5 and could be exploited in point-of-care (POC) testing of active PTB at all levels of health care, and potentially in households and the community. 6,7 In addition to being safer to handle, normal urine production yields frequent and relatively large amounts, making urine specimens convenient to obtain and easier to test in comparison to sputum. Children could benefit the most from urine NAATs for PTB diagnosis due to challenges in obtaining sputum samples, particularly from young children who cannot expectorate, and the paucibacillary nature of their disease. 5,8 With the advancement of molecular techniques and wider use of the NAAT Xpert ® MTB/RIF assay (Cepheid, Sunnyvale, CA, USA) in many high TB endemic countries, exploration of alternative samples such as urine for TB diagnosis is increasing due to its ease of collection and potential for decentralized implementation. 9,10 Cell-free nucleic acids released from dying human cells and Mycobacterium tuberculosis microorganisms may be filtered through the kidneys, resulting in the detection of trans-renal DNA fragments in urine. 6 Although the exact pathophysiological mech...