Comparative performance of urinary lipoarabinomannan assays and Xpert MTB/RIF in HIV-infected individuals

Abstract

Background: Xpert MTB/RIF ('Xpert') and urinary lipoarabinomannan (LAM) assays offer rapid tuberculosis (TB) diagnosis, but have suboptimal sensitivity when used individually in HIV-positive patients. The yield of these tests used in combination for the diagnosis of active TB among HIV-infected TB suspects is unknown.

Design: Study of comparative diagnostic accuracy nested into a prospective study of HIV-infected individuals with signs and/or symptoms of TB in Uganda.

Methods: Xpert testing of archived sputum was conducted for culture-confirmed TB cases and TB suspects in whom a diagnosis of TB was excluded. Additional testing included sputum smear microscopy, sputum culture (solid and liquid media), mycobacterial blood culture, and urinary testing for LAM using a lateral flow test ('LF-LAM') and an enzyme-linked immunosorbance assay ('ELISA-LAM').

Results: Among 103 participants with culture-confirmed TB, sensitivity of Xpert was 76% (95% confidence interval, CI 0.66-0.84), and was superior to that of LF-LAM (49%, 95% CI 0.39-0.59, P < 0.001). Specificity was greater than 97% for both tests among 105 individuals without TB. The combination of smear microscopy and LF-LAM identified 67% (95% CI 0.57-0.76) of culture-confirmed TB cases and approached sensitivity of Xpert testing alone (P = 0.15). The sensitivity of the combination of Xpert and LF-LAM was 85% (88/103 95% CI 0.77-0.92), which was superior to either test alone (P < 0.05) and approached sensitivity of sputum liquid culture testing (94%, 95% CI 0.88-0.98, P = 0.17).

Conclusion: Sputum Xpert and urinary LAM assays were complementary for the diagnosis of active TB in HIV-infected patients, and sensitivity of the combination of these tests was superior to that of either test alone.

Fig. 1. Sensitivity and incremental sensitivity of combinations of diagnostic tests among HIV-infected adults with culture-confirmed tuberculosis

Sensitivity of individual tests and combinations of tests are shown, along with relative contributions. Error bars represent 95% confidence intervals. Performed individually, FM identified 42% of tuberculosis (TB) cases, urine LF-LAM/grade 2 identified 49% of TB cases, and Xpert identified 76% of TB cases. Addition of urinary LF-LAM/grade 2 testing to FM identified an additional 25% of TB cases, resulting in a sensitivity of 67% for the two-test combination. Addition of one sputum Xpert to the combination of FM and LF-LAM/grade 2 identified another 19% of TB cases, resulting in sensitivity of 86% for the three-test combination. The combination of Xpert and LF-LAM/grade 2 identified 85% of TB cases, a sensitivity similar to that of two sputa cultured in MGIT media (P =0.17). ELISA-LAM, urine enzyme-linked immunosorbance assay for LAM; FM, florescence microscopy on two sputa; LAM, lipoarabinomannan; LF-LAM, urine lateral flow LAM assay; LJ, Lowenstein–Jensen solid culture on two sputa; MGIT, mycobacteria growth indicator tube liquid culture on two sputa; Xpert, Xpert MTB/RIF test on one sputum; ZN, Ziehl–Neelsen on two sputa.