Test characteristics and potential impact of the urine LAM lateral flow assay in HIV-infected outpatients under investigation for TB and able to self-expectorate sputum for diagnostic testing

Abstract

BackgroundThe commercially available urine LAM strip test, a point-of-care tuberculosis (TB) assay, requires evaluation in a primary care setting where it is most needed. There is currently inadequate data to guide implementation in TB and HIV-endemic settings.MethodsAdult HIV-infected outpatients with suspected pulmonary TB able to self-expectorate sputum from four primary clinics in South Africa, Zambia and Tanzania underwent diagnostic evaluation [sputum smear microscopy, Xpert-MTB/RIF, and culture (reference standard)] as part of a prospective parent study. Urine LAM testing (grade-2 cut-point) was performed on archived samples. Performance characteristics of LAM alone or in combination with sputum—based diagnostics were evaluated. Potential impact on 2 and 6-month morbidity (TBscore), patient dropout rates, and prognosis (death/ loss to follow-up) were evaluated.ResultsAmong 583 participants with suspected TB that were HIV-infected or refused testing, the overall LAM sensitivity (95 % CI; n/N) and in the CD4 ≤ 100 cells/mm3 sub-group was 22.7 % (16.6-28.7; 41/181) and 30.4 % (17.1-43.7; 14/46), respectively. Overall specificity was 93.0 % (90.5-95.6; 361/388). Amongst culture-positive TB cases, adjunctive LAM testing did not improve the sensitivity of either sputum Xpert-MTB/RIF [78.2 % (69.8-86.7; 72/92) versus 76.1 % (67.4-84.8; 70/92), p = 0.7] or smear-microscopy [56.2 % (45.9-66.5; 50/89) versus 43.8 % (33.5-54.1; 39/89), p = 0.1). Clinic-based LAM, as an adjunct to either smear microscopy or Xpert MTB/RIF same-day testing, would neither have decreased patient dropout, nor increased same-day treatment initiation in this clinical setting where same-day chest radiography was available. LAM positivity was associated with 6-month lost-to-follow-up/death (AOR 4.4; p = 0.002) but not TBscore (at baseline or change in TBscore 2-months post-treatment) (p = 0.17).ConclusionsIn African HIV-TB co-infected outpatients able to self-expectorate sputum LAM had limited sensitivity even at low CD4 counts, and offered no significant incremental diagnostic yield over Xpert-MTB/RIF or smear microscopy. In primary care clinics with chest radiography and where empiric TB treatment is common, LAM seems unlikely to improve rates of same-day treatment initiation and patient dropout, however, the ability of LAM to identify patients at high risk of death or lost-to-follow-up may offer important prognostic value.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-0967-z) contains supplementary material, which is available to authorized users.

Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults

“…In addition, we excluded one ongoing study ( Grant ongoing ) which remained unpublished as of December 2015. Therefore, we included 12 unique studies in this review ( Andrews 2014 ; Balcha 2014 ; Bjerrum 2015 ; Drain 2014b ; Drain 2014a ; Drain 2014c ; LaCourse 2015 ; Lawn 2012a ; Lawn 2014a ; Nakiyingi 2014 ; Peter 2012a ; Peter 2015 ). We listed the excluded studies and reasons for their exclusion in the ' Characteristics of excluded studies ' section.…”

“…For the purpose of TB diagnosis, six studies contributed data ( Figure 3 ). In the patient selection domain, we considered two studies (33%) to be at high risk of bias because: (1) the study excluded all smear‐positive participants ( Drain 2014c ); (2) the study excluded participants who were unable to expectorate sputum ( Peter 2015 ). All studies were cross‐sectional or cohort studies.…”

“…In the reference standard domain, we considered four studies (66%) to be at high risk of bias because: (1) the study only conducted mycobacterial blood culture as the reference standard without testing of respiratory specimens ( Andrews 2014 ); (2) the studies did not include testing of extrapulmonary specimens ( Drain 2014c ; Peter 2015 ); and (3) health providers selected the sites for testing based on their own clinical suspicion ( Peter 2012a ). In terms of applicability, we deemed one study at high concern because of a lack of study directed testing ( Peter 2012a ).…”

“… 1 We used QUADAS‐2 to assess risk of bias. We considered one study to be at high risk of bias because this study excluded patients who were unable to produce sputum ( Peter 2015 ). We did not downgrade the evidence.…”

“…4 We used QUADAS‐2 to assess risk of bias. We considered three studies to be at high risk of bias because they used a lower quality reference standard ( Andrews 2014 ; Peter 2012a ; Peter 2015 ). We downgraded the evidence by one level.…”