Determine TB-LAM, a urine antigen test for pumonary tuberculosis screening, proved reasonably sensitive in HIV-positive people with low CD4 counts, according to results of a 500-patient study at an antiretroviral clinic in Gugulethu township, South Africa. Sensitivity improved when Determine TB-LAM was combined with sputum smear microscopy.
TB and HIV are both epidemic in many countries, and early diagnosis and treatment of both infections are critical to slowing their transmission. But sputum smear microscopy and chest x-rays have poor diagnostic accuracy, and culture-based diagnosis is slow, expensive, and often unavailable in regions with coepidemic TB and HIV.
South African researchers planned this study of consecutive adults referred to a community-based antiretroviral therapy clinic. All study participants were screened by TB by fluorescence microscopy, automated liquid culture (the gold-standard test), the Xpert MTB/RIF assay, and the urine-based Determine TB-LAM test.
People with one or more sputum samples positive for Mycobacterium tuberculosis were defined as having TB. The investigators compared the diagnostic accuracy of Determine TB-LAM alone and combined with sputum smear microscopy with results of sputum culture and Xpert MTB/RIF for patients in different CD4 subgroups.
From March 2010 through April 2011, researchers recruited 602 patients, 542 of whom provided one or more sputum samples. Ninety-four people had culture-positive TB for a prevalence of 17.4% (95% confidence interval [CI] 14.2 to 20.8).
Complete diagnostic test results were available for 516 patients, who had a median CD4 count of 169.5 cells/μL (interquartile range 100 to 233). This group included 85 people with culture-positive TB, 24 of whom (28.2%, 95% CI 19.0 to 39.0) had sputum smear-positive disease. Determine TB-LAM strips provided diagnostic results within 30 minutes, and agreement on test results by two independent readers was high (κ = 0.97).
Determine TB-LAM proved reasonably sensitive compared with sputum culture: 66.7% (95% CI 41.0% to 86.7%) at CD4 counts less than 50 cells/μL, 51.7% (32.5% to 70.6%) at less than 100 cells/μL, and 39.0% (26.5% to 52.%6) at less than 200 cells/μL. Specificity was greater than 98% in all CD4 brackets. (Sensitivity is the ability of a test to single out people who have a certain disease. Specificity is the ability of the test to classify people who do not have the disease as negative.)
Sensitivity improved when Determine TB-LAM was combined with smear microscopy and a positive result on either test was considered diagnostic: 72.2% (95% CI 46.5% to 90.3%) at CD4 counts less than 50 cells/μL, 65.5% (45.7% to 82.1%) at less than 100 cells/μL, and 52.5% (39.1% to 65.7%) at less than 200 cells/μL.
The researchers conclude that “Determine TB-LAM is a simple, low-cost, alternative to existing diagnostic assays for tuberculosis screening in HIV-infected patients with very low CD4 cell counts and provides important incremental yield when combined with sputum smear microscopy.”
Source: Stephen D. Lawn, Andrew D. Kerkhoff, Monica Vogt, Robin Wood. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infectious Diseases. 2012; 12: 201-209.