Abstract
BackgroundDiagnosis 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.MethodsWe 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.ResultsWe 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).ConclusionsIn 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.
Highlights
Diagnosis of extrapulmonary tuberculosis (TB) remains challenging
In hospitalized Ugandans with advanced human immunodeficiency virus (HIV) disease and suspected meningitis, systematic screening with urine TB-LAM and Ultra found a high prevalence of urine TB test positivity (26%)
Participants with suspected or confirmed TB meningitis were categorized according to the 2010 uniform case definition; with “definite TB meningitis” comprising those with microbiologically confirmed M tuberculosis in cerebrospinal fluid (CSF) and “probable TB meningitis” comprising those who score ≥10 points on clinical, CSF, and imaging criteria but who are negative for TB on CSF testing [24]
Summary
We prospectively enrolled human immunodeficiency virus (HIV)-positive adults with suspected meningitis in Uganda during 2018–2020. Inclusion criteria for diagnostic testing were HIV-positive adults (≥18 years) presenting with suspected meningitis (eg, headache or altered mental status, clinical signs of meningism). From March 27, 2018 to February 6, 2020, urine-based screening for TB was conducted using an Alere Determine TB-LAM LFA assay (TB-LAM; Alere) and Xpert Ultra (Cepheid). Participants with suspected or confirmed TB meningitis were categorized according to the 2010 uniform case definition; with “definite TB meningitis” comprising those with microbiologically confirmed M tuberculosis in CSF and “probable TB meningitis” comprising those who score ≥10 points (or ≥12 points if brain imaging is performed) on clinical, CSF, and imaging criteria but who are negative for TB on CSF testing [24]. Due to its low specificity in a high HIV-burden setting “possible TB meningitis” was not included as a discrete diagnostic category
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