Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults

Abstract

Objective: In settings of high HIV prevalence, tuberculosis control and patient management are hindered by lack of accurate, rapid tuberculosis diagnostic tests that can be performed at point-of-care. The Determine TB LAM Ag (TB LAM) test is a lateral flow immunochromatographic test for detection of mycobacterial lipoarabinomannan (LAM) in urine. Our objective was to determine sensitivity and specificity of the TB LAM test for tuberculosis diagnosis.

Design: Prospective diagnostic accuracy study.

Setting: Hospital and outpatient settings in Uganda and South Africa.

Participants: HIV-infected adults with tuberculosis symptoms and/or signs.

Methods: Participants provided a fresh urine specimen for TB LAM testing, blood for mycobacterial culture, and 2 respiratory specimens for smear microscopy and mycobacterial culture.

Main outcome measures: For the TB LAM test, sensitivity in participants with culture-positive tuberculosis and specificity in participants without tuberculosis.

Results: A total of 1013 participants were enrolled. Among culture-positive tuberculosis patients, the TB LAM test identified 136/367 (37.1%) overall and 116/196 (59.2%) in the group with CD4 ≤100 cells per cubic millimeter. The test was specific in 559/573 (97.6%) patients without tuberculosis. Sensitivity of the urine TB LAM test plus sputum smear microscopy was 197/367 (53.7%) overall and 133/196 (67.9%) among those with CD4 ≤100. CD4 ≤50 [adjusted odds ratio (AOR), 6.2; P < 0.001] or 51-100 (AOR, 7.1; P < 0.001), mycobacteremia (AOR, 6.1; P < 0.01) and hospitalization (AOR, 2.6; P = 0.03) were independently associated with a positive TB LAM test.

Conclusions: In HIV-positive adults with CD4 ≤100, the TB LAM urine test detected over half of culture-positive tuberculosis patients, in <30 minutes and without the need for equipment or reagents.

Trial registration: ClinicalTrials.gov NCT01525134 NCT01693224.

Conflict of interest statement

Conflicts of Interest: None of the authors has a commercial or other association that might pose a conflict of interest. Alere had no role in study design, in the collection, analysis, or interpretation of data, in the writing of this manuscript, or in the decision to submit this manuscript for publication.

Figures

Figure 1

Flow of study participants. *Among these 14 participants, 4 (28.6%) had enrollment mycobacterial blood cultures that were not evaluable for M. tuberculosis (blood culture not performed in one participant, and blood cultures overgrown with a non-mycobacterial organism not subjected to species identification for 3 participants); all other enrollment respiratory and blood cultures were evaluable. Among these 14 participants, 7 (50.0%) died before the two-month follow-up visit, 3 (21.4%) were lost/not able to be contacted for the two-month follow-up visit, 3 (21.4%) completed study follow-up including one who had a blood culture positive for M. tuberculosis at follow-up, and one (7.1%) withdrew consent.

Figure 2

(A) Receiver-operator characteristic curve for the Determine TB LAM Ag assay. The integers adjacent to points on the graph correspond to grade 1, grade 2, grade 3, grade 4, grade 5, and refer to minimum test band intensity required for characterization of a test result as positive. (B) Determine TB LAM Ag test sensitivity among participants with culture-positive tuberculosis and specificity among participants with no evidence of tuberculosis, using a positivity threshold of grade 2 and stratified by CD4 count (in cells/mm3).

Figure 2

(A) Receiver-operator characteristic curve for the Determine TB LAM Ag assay. The integers adjacent to points on the graph correspond to grade 1, grade 2, grade 3, grade 4, grade 5, and refer to minimum test band intensity required for characterization of a test result as positive. (B) Determine TB LAM Ag test sensitivity among participants with culture-positive tuberculosis and specificity among participants with no evidence of tuberculosis, using a positivity threshold of grade 2 and stratified by CD4 count (in cells/mm3).