Diagnostic accuracy of a point-of-care urine test for tuberculosis screening among newly-diagnosed HIV-infected adults: a prospective, clinic-based study

Abstract

Background: A rapid diagnostic test for active tuberculosis (TB) at the clinical point-of-care could expedite case detection and accelerate TB treatment initiation. We assessed the diagnostic accuracy of a rapid urine lipoarabinomannan (LAM) test for TB screening among HIV-infected adults in a TB-endemic setting.

Methods: We prospectively enrolled newly-diagnosed HIV-infected adults (≥18 years) at 4 outpatient clinics in Durban from Oct 2011-May 2012, excluding those on TB therapy. A physician evaluated all participants and offered CD4 cell count testing. Trained study nurses collected a sputum sample for acid-fast bacilli smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing using Determine™ TB LAM in the clinic. The presence of a band regardless of intensity on the urine LAM test was considered positive. We defined as the gold standard for active pulmonary TB a positive sputum culture for Mycobacterium tuberculosis. Diagnostic accuracy of urine LAM was assessed, alone and in combination with smear microscopy, and stratified by CD4 cell count.

Results: Among 342 newly-diagnosed HIV-infected participants, 190 (56%) were male, mean age was 35.6 years, and median CD4 was 182/mm3. Sixty participants had culture-positive pulmonary TB, resulting in an estimated prevalence of 17.5% (95% CI 13.7-22.0%). Forty-five (13.2%) participants were urine LAM positive. Mean time from urine specimen collection to LAM test result was 40 minutes (95% CI 34-46 minutes). Urine LAM test sensitivity was 28.3% (95% CI 17.5-41.4) overall, and 37.5% (95% CI 21.1-56.3) for those with CD4 count <100/mm3, while specificity was 90.1% (95% CI 86.0-93.3) overall, and 86.9% (95% CI 75.8-94.2) for those with CD4 < 100/mm3. When combined with sputum AFB (either test positive), sensitivity increased to 38.3% (95% CI 26.0-51.8), but specificity decreased to 85.8% (95% CI 81.1-89.7).

Conclusions: In this prospective, clinic-based study with trained nurses, a rapid urine LAM test had low sensitivity for TB screening among newly-diagnosed HIV-infected adults, but improved sensitivity when combined with sputum smear microscopy.

Figure 1

Participant flow diagram.

Figure 2

Urine LAM and sputum smear microscopy (AFB) to diagnose tuberculosis among those who were either culture-confirmed (Figure 2a) or diagnosed with clinically suspected (Figure 2b) tuberculosis. a. Culture-confirmed Pulmonary Tuberculosis (N = 60). b. Clinically Suspected Tuberculosis (N = 92). Any participant who were LAM + but not diagnosed with culture-confirmed or clinically suspected tuberculosis are not depicted in these figures.

Figure 3

Post-test probability of tuberculosis when using a combined screening strategy of sputum AFB and urine LAM testing for various pre-test probabilities. Column A represents a cohort with 10% prevalence of tuberculosis; columns B and C represent the baseline prevalence of culture-positive pulmonary tuberculosis (17.5%) and clinically suspected tuberculosis (26.9%) that we observed in our cohort. Column D represents a cohort with a 40% prevalence of tuberculosis, which might occur among tuberculosis suspects in a highly endemic region.