Diagnostic Accuracy of a Urine Lipoarabinomannan Enzyme-Linked Immunosorbent Assay for Screening Ambulatory HIV-Infected Persons for Tuberculosis

Abstract

Objective To assess the diagnostic accuracy of the urine lipoarabinomannan (LAM) test among ambulatory HIV-infected persons. Design Cross-sectional Methods HIV-infected persons consecutively presenting to the HIV Clinic at Tembisa Main Clinic in Ekhuruleni, South Africa were screened for symptoms of tuberculosis (TB), and asked to provide sputum and blood samples for smears for acid-fast bacilli (AFB) and mycobacterial culture, and a urine specimen for a LAM enzyme-linked immunosorbent assay (ELISA). Fine needle aspirates were obtained from participants with enlarged lymph nodes, and sent for histopathology. Non-pregnant participants underwent chest x-ray. Results 422 HIV-infected participants were enrolled with median age 37 years [interquartile range (IQR) 31-44 years], median CD4+ T-cell count 215 cells/μL (IQR 107-347 cells/μL), and 212 (50%) receiving antiretroviral therapy (ART). 30 (7%) had active TB: 18 with only pulmonary TB (PTB), 5 with only extrapulmonary TB (ETB), and 7 with both PTB and ETB. 27% (95% CI 12-48%) of TB cases were sputum AFB-positive. The sensitivity and specificity of the urine LAM compared to the gold standard of positive bacteriology or histopathology were 32% (95% confidence interval [CI] 16-52%) and 98% (95% CI 96-99%) respectively. Urine LAM had higher sensitivity in TB cases with higher bacillary burdens, though these differences were not statistically significant. Conclusions The sensitivity of urine LAM testing is inadequate to replace mycobacterial culture. In contrast to prior research on the urine LAM, this study was conducted among less sick, ambulatory HIV-infected patients presenting for routine care.

Test Characteristics of Urinary Lipoarabinomannan and Predictors of Mortality among Hospitalized HIV-Infected Tuberculosis Suspects in Tanzania

“…The effect of different patient populations is most evident with HIV where sensitivity has been found to be higher in HIV-positive than in HIV-negative patients and higher with decreasing CD4 count, as we also observed [8], [13]. This could reflect a higher circulating burden of M. tuberculosis in advanced AIDS as suggested by a study that showed higher sensitivity with positive blood cultures [9].…”

Improving tuberculosis diagnostics with biomarkers

“…52,53 Although the sensitivity of many TB diagnostic tests declines in HIV-infected patients with advanced immunodeficiency, the sensitivity of urine LAM test paradoxically increases, whereas CD4 lymphocyte counts decrease. 54 Currently, a low cost and point-of-care TB diagnostic test in HIV patients is now being developed with urine antigen detection.…”

Hyperthermostable binding molecules on phage: Assay components for point-of-care diagnostics for active tuberculosis infection

“…Sensitivity and specificity for TB diagnostics are measured in relation to culture-based screening. Another 4 studies on LAM ELISA screens showed consistently poor overall performance with sensitivities ranging from 13% to 51% [12][13][14][15]. The combined studies suggest little consistency for the detection of urine LAM in patients with suspected TB [8].…”