Value of urine-based lipoarabinomannan (LAM) antigen tests for diagnosing tuberculosis in children: systematic review and meta-analysis

BACKGROUND: Tuberculosis (TB) is a global burden, and this is likely to remain the case due to a lack of adequate and accurate point-of-care diagnostic tests. Obtaining good-quality sputum from the bottom of the respiratory tract of children is challenging. Lipoarabinomannan (LAM) is a specific component of the mycobacterial cell envelope that is excreted in the urine of people with active TB. This study aimed to assess the performance of different types of urine-based LAM antigen tests for the diagnosis of TB in children. METHODS: Relevant databases were searched for studies that used urine-based LAM tests to diagnose TB in children. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Tool. Pooled sensitivity and specificity were calculated using the random-effect model in STATA Version 16.0. Moreover, subgroup analysis was undertaken to hinder the heterogeneity of the studies. RESULTS: Eleven articles were included in the final systematic review and meta-analysis. The pooled sensitivity and specificity of the Mycobacterium tuberculosis enzyme-linked immunosorbent assay (MTB-LAM-ELISA), Alere Determine TB LAM Ag (Alere LAM) test and the Fujifilm SILVAMP TB LAM (Fuji LAM) test in children aged <15 years with TB were 16.0% [95% confidence interval (CI) 10.25–42.25] and 95.61% (95% CI 93.74–97.74); 45.90% (95% CI 40.40–51.40) and 80.42% (95% CI 69.39–91.46); and 52.32% (95% CI 35.03–69.62) and 89.37% (95% CI 82.88–95.86), respectively. Subgroup analysis revealed that the pooled sensitivity and specificity of MTB-LAM-ELISA, Alere LAM test and Fuji LAM test were 33.5% (95% CI 34.86–100) and 95.83% (95% CI 91.50–100); 46.59% (95% CI 32.98–60.19) and 76.45% (95% CI 57.07–95.82); and 57.89% (95% CI 48.44–67.35%) and 87.66% (95% CI 75.29–100), respectively, in human immunodeficiency virus (HIV)-positive children; and 3.35% (95% CI 1.61–8.31) and 96.0% (95% CI 93.88–98.11); 32.33% (95% CI 7.63–57.03) and 79.07% (95% CI 62.62–95.51); and 50.95% (95% CI 27.45–74.45) and 89.47% (95% CI 84.72–94.22), respectively, in HIV-negative children. CONCLUSION: The Fuji LAM and Alere LAM tests may be useful for the diagnosis of TB in children in conjunction with other more sensitive and specific tests, although a prospective study in relevant clinical settings is needed to evaluate this. There is a need for more evidence-based data on the use of these rapid diagnostic tools to diagnose TB in children independent of HIV status.