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

Fiona V Cresswell; Jayne Ellis; Enock Kagimu; Ananta S Bangdiwala; Michael Okirwoth; Gerald Mugumya; Morris Rutakingirwa; John Kasibante; Carson M Quinn; Kenneth Ssebambulidde; Joshua Rhein; Edwin Nuwagira; Lillian Tugume; Emily Martyn; Caleb P Skipper; Conrad Muzoora; Daniel Grint; David B Meya; Nathan C Bahr; Alison M Elliott; David R Boulware

doi:10.1093/ofid/ofaa100

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

Open Forum Infect Dis. 2020 Mar 24;7(4):ofaa100. doi: 10.1093/ofid/ofaa100. eCollection 2020 Apr.

Authors

Fiona V Cresswell^{1

2

3}, Jayne Ellis⁴, Enock Kagimu¹, Ananta S Bangdiwala⁵, Michael Okirwoth¹, Gerald Mugumya⁶, Morris Rutakingirwa¹, John Kasibante¹, Carson M Quinn¹, Kenneth Ssebambulidde¹, Joshua Rhein^{1

7}, Edwin Nuwagira⁸, Lillian Tugume¹, Emily Martyn¹, Caleb P Skipper^{1

9}, Conrad Muzoora⁸, Daniel Grint¹⁰, David B Meya^{1

9}, Nathan C Bahr⁷, Alison M Elliott^{2

3}, David R Boulware⁹

Affiliations

¹ Infectious Diseases Institute, Makerere University, Kampala, Uganda.
² Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom.
³ MRC-UVRI-London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
⁴ Hospital for Tropical Diseases, University College London Hospitals NHS Foundation Trust, London, United Kingdom.
⁵ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
⁶ Microbiology Laboratory, Kiruddu Referral Hospital, Kampala, Uganda.
⁷ Division of Infectious Diseases, Department of Medicine, University of Kansas, Kansas City, Kansas, USA.
⁸ Mbarara University of Science and Technology, Mbarara, Uganda.
⁹ Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
¹⁰ Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom.

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.

Keywords: HIV; TB-LAM; Xpert MTB/RIF Ultra; meningitis; tuberculosis.

Abstract

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