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. ElliottDavid R. Boulware

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article numberofaa100
JournalOpen Forum Infectious Diseases
Volume7
Issue number4
DOIs
StatePublished - 2020

Bibliographical note

Funding Information:
Financial support. This work was funded by a Wellcome Trust Clinical PhD Fellowship (Grant 210772/Z/18/Z; to F. V. C.), the National Institute of Neurologic Disorders and Stroke (R01NS086312 and K23NS110470; to D. R. B. and D. B. M.), the Fogarty International Center (K01TW010268; to J. R.), and the National Institute of Allergy and Infectious Diseases (T32AI055433 and R01AI145437; to D. R. B. and D. B. M.). F. V. C. is an honorary fellow of the Makerere University—Uganda Virus Research Institute Centre of Excellence for Infection and Immunity Research and Training (MUII-plus). MUII-plus is supported through the DELTAS Africa Initiative (Grant no. 107743). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS), Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (Grant no. 107743) and the UK Government. The MRC/UVRI and LSHTM Uganda Research Unit is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the European and Developing Countries Clinical Trials Partnership (EDCTP)-2 programme supported by the European Union.

Publisher Copyright:
© 2020 Oxford University Press. All rights reserved.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • HIV
  • Meningitis
  • TB-LAM
  • Tuberculosis
  • Xpert MTB/RIF Ultra

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