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 (DetermineTM 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/mm3 (IQR 89–256/mm3). 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/mm3. Urine LAM testing may be most beneficial among patients with functional impairment, elevated inflammatory markers, or greater immunosuppression.