Diagnostic Accuracy of a Urine Lipoarabinomannan Test for Tuberculosis in Hospitalized Patients in a High HIV Prevalence Setting

Abstract

Background Effective tuberculosis (TB) control in HIV-prevalent settings is hindered by absence of accurate, rapid TB diagnostic tests. We evaluated the accuracy of a urine lipoarabinomannan (LAM) test for TB diagnosis in South Africa. Methods Hospitalized adults with signs and/or symptoms of active TB were enrolled. Sputum smear microscopy and mycobacterial culture, mycobacterial blood culture, and HIV testing were performed. A spot urine specimen was tested for LAM. Results 499 participants were enrolled; 422 (84.6%) were HIV-infected. In microbiologically-confirmed TB patients, the LAM test was positive in 114/193 (sensitivity 59%, [95% CI 52, 66]), including 112/167 (67% [59, 74]) who were HIV-infected. Among individuals classified as “not TB”, the LAM test was negative in 117/122 (specificity 96% [91, 99]), including 83/88 (94% [87, 98]) who were HIV-infected. In confirmed TB patients, the LAM test was more sensitive than sputum smear microscopy (42%, 82/193, p<0.001) and detected 56% (62/111) of those who were sputum smear-negative. HIV-infection (AOR 13.4), mycobacteremia (AOR 3.21), and positive sputum smear (AOR 2.42) were risk factors for a positive LAM test. Conclusions The urine LAM test detected a subset of HIV-infected patients with severe TB in whom sputum smear microscopy had suboptimal sensitivity. The combination of urine LAM testing and sputum smear microscopy is attractive for use in settings with high HIV burden.

Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and meta-analysis

“…However, we also found that LAM was positive in 41% of smear-negative specimens; this is a relatively large incremental yield compared with smear microscopy. This suggests that the LAM assay and smear microscopy may detect different groups of TB patients, and might be best used in combination, as was reported by SHAH et al [23].…”

“…Meta-regression was performed using the overall proportion of HIV-positive TB suspects in each study as an independent TESSEMA [18] BOEHME [19] REITHER [20] MUTETWA [21] SHAH [23] DHEDA [25] HAMASUR [17] TESSEMA [18] BOEHME [19] REITHER [20] MUTETWA [21] SHAH [23] DHEDA [25] TESSEMA [18] BOEHME [19] REITHER [20] MUTETWA [21] LAWN [22] SHAH [23] DALEY [24] DHEDA [25] QUADAS criteria…”

Quantitative Analysis of a Urine-Based Assay for Detection of Lipoarabinomannan in Patients with Tuberculosis

“…Our group and others have recently reported on the qualitative diagnostic accuracy of this urine LAM test (9,10,16). Urine LAM test sensitivity, while imperfect, appears to be higher than that of sputum smear microscopy, and the test performs with a high positive predictive value in populations with high HIV and TB prevalence (9,12,16). However, quantitative urine LAM test results have not been studied fully.…”

“…Sputum smear microscopy is widely utilized to diagnose active TB but has impaired sensitivity and detects less than half of HIV-TB coinfection cases (2,6,8). Mycobacterial culture is the laboratory standard for diagnosis but is not widely available in resource-constrained settings and can take weeks to determine a positive result.The detection of lipoarabinomannan (LAM), a 17.5-kDa glycolipid component of the mycobacterial cell wall, is an attractive approach to diagnosing active TB (1,7,9,15,16). LAM is released from metabolically active mycobacteria and is detectable intact in urine (1, 7).…”

Novel Developments in the Epidemic of Human Immunodeficiency Virus and Tuberculosis Coinfection

“…However, one study showed high sensitivity for detecting TB in smearpositive sputum from HIV-infected subjects, using the AMPLI-COR PCR (Roche Diagnostic Systems, Branchburg, NJ) (99.7%), and no significant difference in sensitivity compared with smear-negative culture-positive specimens from HIV-negative subjects (89 vs. 95%) (108). Urine detection of the MTb cell wall component lipoarabinomannan may improve detection in smear-negative HIV-infected patients with advanced immunosuppression in a high-prevalence setting (109,110). Serological tests currently have no proven role in the diagnosis of active TB with or without HIV (111) and IFN-g release assays (IGRAs) do not help to distinguish latent from active TB (63).…”