Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana–findings from the DETECT HIV-TB study

Abstract

BackgroundRapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy.MethodsHIV-infected adults eligible for antiretroviral therapy were prospectively enrolled from Korle-Bu Teaching Hospital in Ghana and followed for minimum 6 months. We applied the LAM test on urine collected as a spot and early morning sample. Diagnostic accuracy was analysed for a microbiological TB reference standard based on sputum culture and Gene Xpert MTB/RIF results and for a composite reference standard including clinical follow-up data. Performance of sputum smear microscopy was included for comparison.ResultsOf 469 patients investigated for TB, the LAM test correctly identified 24/55 (44 %) of microbiologically confirmed TB cases. Sensitivity of the LAM test was positively associated with hospitalisation (67 %), Modified Early Warning Score > 4 (57 %) and subsequent death (71 %). LAM test specificity was 95 % increasing to 98 % for the composite reference standard. A two-sample LAM test strategy did not improve test performance. Using concentrated sputum for Ziehl-Neelsen and fluorescence microscopy in combination yielded a sensitivity of 31/55 (56 %) that increased to 35/55 (64 %) when the LAM test was added. Surprisingly, nontuberculous mycobacteria were cultured in 34/469 (7 %) and associated with a positive LAM test (p = 0.008).ConclusionsLAM test sensitivity was highest in patients with poor prognosis and subsequent death and did not increase with a two-sample strategy. A rigorous sputum microscopy strategy had superior sensitivity, but the simplicity of the LAM test holds operational possibilities as a TB screening method among severely sick patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1151-1) contains supplementary material, which is available to authorized users.

Utility of urine lipoarabinomannan (LAM) in diagnosing tuberculosis and predicting mortality with and without HIV: prospective TB cohort from the Thailand Big City TB Research Network

“…The LAM test has been proven to be incredibly helpful in probable TB patients with negative smear results who are co-infected with HIV. The data from this study corroborate the diagnostic sensitivity of the urine LAM test, which was reported to be between 44% and 63% in hospitalized HIV-positive patients in South Africa and Uganda (Fielding et al, 2015;Lawn et al, 2013;Seddiki et al, 2014;Bjerrum et al, 2015;Shah et al, 2014).…”

Tuberculosis and non‐tuberculous mycobacteria among HIV‐infected individuals in Ghana

“…This was a prospective observational study of HIV‐infected individuals enrolled between January 2013 and March 2014 with 6 months of follow‐up. The study is based on data from a recently reported diagnostic accuracy study of the rapid urine lipoarabinomannan (LAM) test for TB diagnosis in Ghana . In brief, the study was conducted at the Fevers Unit, Korle‐Bu Teaching Hospital in the capital city of Accra.…”

Design and use of mouse control DNA for DNA biomarker extraction and PCR detection from urine: Application for transrenal Mycobacterium tuberculosis DNA detection

“…Molecular testing using the Cepheid GeneXpert® MTB/RIF is increasing in high disease burden areas[13,25,26], and has been evaluated using urine samples [13,27,28] but sensitivity is variable, particularly among HIV-infected patients [21,25,26,29]. But implementation of GeneXpert has been limited by cartridge stock-outs, the need for a continuous electricity, temperature control during specimen transport, as well as human resource limitations [16,30–32].…”