Urine-based diagnostic tests for tuberculosis: a scoping review highlighting unmet diagnostic needs

Current diagnostics for tuberculosis (TB) rely on sputum or site-specific specimen collection, posing critical limitations in certain populations. Urine has emerged as an alternative specimen, as demonstrated by urine lipoarabinomannan (LAM) testing. Beyond LAM, no urine-based tests are established for clinical use, and evidence for non-LAM urine antigen tests and urine-based nucleic acid amplification tests (NAATs) remains inconsistently synthesized. This scoping review aimed to comprehensively map current evidence and identify gaps in urine-based diagnostic tests for TB.

We conducted a scoping review across three databases (PubMed, Scopus, and Embase) of studies evaluating urine-based diagnostic tests for TB and reporting diagnostic performance metrics, extracting data on urine test type, country, TB disease type, study population, and HIV status. Findings were summarized descriptively and visualized to illustrate trends. We also extracted technical approaches for urine-based NAATs and urine concentration methods.

In total, 208 publications reporting 274 urine-based tests published between 1995 and 2024 were included. Most studies were conducted in high-burden settings and focused on pulmonary TB (44.7%), adult populations (62.5%), and people living with HIV (31.3%). LAM-based tests dominated the literature, accounting for 49.3% (n = 135) of all tests, primarily in lateral flow formats. Non-LAM urine antigen tests were evaluated less frequently (n = 26), typically in small cohorts and laboratory-based assays. Urine-based NAATs showed wide variability in technical approaches. Only a few studies (n = 10) evaluated urine concentration methods.

Evidence for urine-based diagnostic tests for TB remains limited for extrapulmonary TB, children, and non-HIV individuals, despite substantial unmet need. Although urine LAM is the most established assay, evaluations of non-LAM urine antigen tests and urine-based NAATs remain exploratory, with few studies, small cohorts, and predominantly laboratory-based assays. Further research is needed to identify and validate reliable, broadly applicable urine-based diagnostic tests to address these gaps.