Standardized Urine-Based Tuberculosis (TB) Screening With TB-Lipoarabinomannan and Xpert MTB/RIF Ultra in Ugandan Adults With Advanced Human Immunodeficiency Virus Disease and Suspected Meningitis

Abstract

Background Diagnosis of extrapulmonary tuberculosis (TB) remains challenging. We sought to determine the prevalence of disseminated TB by testing urine with TB-lipoarabinomannan (TB-LAM) lateral flow assay and Xpert MTB/RIF Ultra (Ultra) in hospitalized adults. Methods We prospectively enrolled human immunodeficiency virus (HIV)-positive adults with suspected meningitis in Uganda during 2018–2020. Participants underwent standardized urine-based TB screening. Urine (60 mcL) was tested with TB-LAM (Alere), and remaining urine was centrifuged with the cell pellet resuspended in 2 mL of urine for Xpert Ultra testing. Results We enrolled 348 HIV-positive inpatients with median CD4 of 37 cells/mcL (interquartile range, 13–102 cells/mcL). Overall, 26% (90 of 348; 95% confidence interval [CI], 21%–30%) had evidence of disseminated TB by either urine assay. Of 243 participants with both urine TB-LAM and Ultra results, 20% (48 of 243) were TB-LAM-positive, 12% (29 of 243) were Ultra-positive, and 6% (14 of 243) were positive by both assays. In definite and probable TB meningitis, 37% (14 of 38) were TB-LAM-positive and 41% (15 of 37) were Ultra-positive. In cryptococcal meningitis, 22% (40 of 183) were TB-LAM-positive and 4.4% (6 of 135) were Ultra-positive. Mortality trended higher in those with evidence of disseminated TB by either assay (odds ratio = 1.44; 95% CI, 0.83–2.49; P = .19) and was 6-fold higher in those with definite TB meningitis who were urine Ultra-positive (odds ratio = 5.67; 95% CI, 1.13–28.5; P = .04). Conclusions In hospitalized Ugandans with advanced HIV disease and suspected meningitis, systematic screening with urine TB-LAM and Ultra found a high prevalence of urine TB test positivity (26%). In those with TB meningitis, urine tests were positive in over one third. There was little concordance between Ultra and TB-LAM, which warrants further investigation.

High-sensitivity C-reactive protein in HIV care: Tuberculosis diagnosis and short-term mortality in a cohort of Kenyan HIV patients in the DREAM programme

“…Concordance of Xpert MTB/RIF and LF-LAM in this cohort was low, but in line with other studies (Cresswell et al, 2020). In a previous study in Mozambique, a higher concordance was found between the two tests (Floridia et al, 2017); however, these variations could be attributed to different rates of extrapulmonary TB, due to different patient selection criteria.…”

Tuberculosis IRIS: Pathogenesis, Presentation, and Management across the Spectrum of Disease

“…A novel LAM assay has increased sensitivity and thus might allow prevention of unmasking IRIS [123]. Tests of both urine and sputum with GeneXpert MTB/RIF Ultra can also improve detection of TB in PLHIV, and return results quickly enough to allow for providing ATT at the time of ART-initiation [173][174][175], potentially allowing prevention of unmasking IRIS [158].…”

Cerebrospinal Fluid Lactate as a Prognostic Marker of Disease Severity and Mortality in Cryptococcal Meningitis

“…The study included Ugandan adults presenting with first-episode cryptococcal meningitis After conclusion of ASTRO-CM, participants were enrolled in an observational cohort focused on meningitis diagnostics. [12][13][14] All participants enrolled into the studies provided written informed consent. Participants were treated with standard antifungal therapy and those who were enrolled into ASTRO-CM were randomized to either receive adjunctive sertraline (400 mg/day for 14 days, followed by 200 mg/day for 12 weeks) or placebo.…”