Rapid Urine LAM Testing Improves Diagnosis of Expectorated Smear-Negative Pulmonary Tuberculosis in an HIV-endemic Region

Abstract

We sought to determine if urine lipoarabinomannan (LAM) would improve diagnosis of pulmonary TB. We enrolled consecutive adults presenting with ≥2 TB-related symptoms, obtained one induced sputum sample for smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing (Determine(TM) TB LAM, Alere). We used culture-confirmed pulmonary TB as the gold standard, and compared accuracy with area under receiver operating characteristic curves (AUROC). Among 90 participants, 82 of 88 tested (93%) were HIV-infected with a median CD4 168/mm(3) (IQR 89-256/mm(3)). Diagnostic sensitivities of urine LAM and sputum AFB were 42.1% (95% CI 29.1-55.9%) and 21.1% (95% CI 11.4-33.9%), and increased to 52.6% (95% CI 39.0-66.0%) when combined. Sensitivity of LAM increased significantly among participants with a lower Karnofsky Performance score, anemia, hypoalbuminemia, and higher C-reactive protein. Combining LAM with AFB had an AUROC = 0.68 (95% CI 0.59-0.77), significantly better than AFB alone (AUROC=0.58; 95% CI 0.51-0.64). The combination of LAM and AFB was significantly better than AFB alone among patients with Karnofsky Performance score ≤90, hemoglobin ≤10 g/dL, albumin ≤25 g/L, C-reactive protein ≥25 mg/L, or CD4 <200/mm(3). Urine LAM testing may be most beneficial among patients with functional impairment, elevated inflammatory markers, or greater immunosuppression.

Figure 1

ROC curves for induced sputum AFB smear (solid blue line), urine LAM assay (dashed red line), and combination of induced sputum AFB smear or urine LAM assay (irregular green line) for diagnosing culture-confirmed pulmonary TB among the entire cohort.

Figure 2

ROC curves for induced sputum AFB smear (solid blue line), urine LAM assay (dashed red line), and combination of induced sputum AFB smear or urine LAM assay (irregular green line) for diagnosing culture-confirmed pulmonary TB among those with a CD4 count <200/mm³.