Top

BMC Infectious Diseases

Published in:

Open Access 01-12-2021 | Tuberculosis | Research article

The utility of point-of-care urinary lipoarabinomannan testing for the diagnosis of tuberculosis in critically ill patients: a prospective observational study

Authors: Kim de Vasconcellos, Praksha Ramjathan, Dhivendra Singh

Published in: BMC Infectious Diseases | Issue 1/2021

Abstract

Background

Tuberculosis is a major global public health concern. Patients with tuberculosis who require critical care have a high mortality and delay in initiating antituberculous therapy is associated with increased mortality. Lipoarabinomannan (LAM) is a lipopolysaccharide found in the cell wall of Mycobacterium tuberculosis. Urinary LAM may be used as a bedside diagnostic test for tuberculosis.

Methods

The study was a single centre, prospective observational study that compared the utility of urinary LAM with conventional tuberculosis diagnostic modalities in patients with suspected tuberculosis who required intensive care admission. Urinary LAM testing was performed using the Alere Determine TB LAM Ag lateral flow assay test strips. A patient was classified as having confirmed tuberculosis if they met the following criteria: a clinical presentation compatible with tuberculosis, with either a positive TB culture, a positive GeneXpert, or a histological diagnosis of tuberculosis.

Results

Fifty patients were included in the study, with 12 having confirmed tuberculosis. All patients received mechanical ventilation, and the ICU mortality was 60%. Urinary LAM had a sensitivity of 50.0% (95% CI, 21.1 to 78.9%) and a specificity of 84.2% (95% CI, 68.8 to 94.0%) for confirmed tuberculosis.

Conclusion

Urinary LAM allows for rapid bedside diagnosis of tuberculosis in critically ill patients. A positive urinary LAM should prompt consideration to initiate antituberculous treatment while the results of further diagnostic testing are awaited.

World Health Organisation. Global tuberculosis report 2020. Geneva: WHO; 2020.

Tsai T-C, Hung MS, Chen I-C, Chew G, Lee W-H. Delayed diagnosis of active pulmonary tuberculosis in emergency department. Am J Emerg Med. 2008;26(8):888–92. https://doi.org/10.1016/j.ajem.2007.11.036.CrossRefPubMed

Zahar J-R, Azoulay E, Klement E, De Lassence A, Lucet J-C, Regnier B, et al. Delayed treatment contributes to mortality in ICU patients with severe active pulmonary tuberculosis and acute respiratory failure. Intensive Care Med. 2001;27(3):513–20. https://doi.org/10.1007/s001340000849.CrossRefPubMedPubMedCentral

Pablos-Méndez A, Sterling TR, Frieden TR. The relationship between delayed or incomplete treatment and all-cause mortality in patients with tuberculosis. JAMA. 1996;276(15):1223–8. https://doi.org/10.1001/jama.1996.03540150025026.CrossRefPubMed

Shivakoti R, Sharma D, Mamoon G, Pham K. Association of HIV infection with extrapulmonary tuberculosis: a systematic review. Infection. 2017;45(1):11–21. https://doi.org/10.1007/s15010-016-0960-5.CrossRefPubMed

Donovan J, Phu NH, Dung VTM, Quang TP, Nghia HDT, PKN O, et al. Xpert MTB/RIF Ultra versus Xpert MTB/RIF for the diagnosis of tuberculous meningitis: a prospective, randomised, diagnostic accuracy study. The Lancet Infectious Diseases. 2020;20(3):299–307.

Horne DJ, Kohli M, Zifodya JS, Schiller I, Dendukuri N, Tollefson D, Schumacher SG, Ochodo EA, Pai M, Steingart KR. Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2019;6(6):CD009593. https://doi.org/10.1002/14651858.CD009593.pub4. Update in: Cochrane Database Syst Rev. 2021;2:CD009593. PMID: 31173647; PMCID: PMC6555588.

Lawn SD. Point-of-care detection of lipoarabinomannan (LAM) in urine for diagnosis of HIV-associated tuberculosis: a state of the art review. BMC Infect Dis. 2012;12(1):103. https://doi.org/10.1186/1471-2334-12-103.CrossRefPubMedPubMedCentral

Choudhry V, Saxena R. Detection of mycobacterium tuberculosis antigens in urinary proteins of tuberculosis patients. Eur J Clin Microbiol Infect Dis. 2002;21(1):1–5. https://doi.org/10.1007/s10096-001-0651-7.CrossRefPubMed

10.

Achkar JM, Lawn SD, Moosa M-YS, Wright CA, Kasprowicz VO. Adjunctive tests for diagnosis of tuberculosis: serology, ELISPOT for site-specific lymphocytes, urinary lipoarabinomannan, string test, and fine needle aspiration. J Infect Dis. 2011;204(suppl_4):S1130–S41.CrossRef

11.

Bjerrum S, Schiller I, Dendukuri N, Kohli M, Nathavitharana RR, Zwerling AA, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019;10(10):CD011420–CD.PubMed

12.

Lawn SD, Kerkhoff AD, Vogt M, Wood R. Diagnostic accuracy of a low-cost, urine antigen, point-of-care screening assay for HIV-associated pulmonary tuberculosis before antiretroviral therapy: a descriptive study. Lancet Infect Dis. 2012;12(3):201–9. https://doi.org/10.1016/S1473-3099(11)70251-1.CrossRefPubMedPubMedCentral

13.

Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, et al. Effect on mortality of point-of-care, urine-based lipoarabinomannan testing to guide tuberculosis treatment initiation in HIV-positive hospital inpatients: a pragmatic, parallel-group, multicountry, open-label, randomised controlled trial. Lancet (London, England). 2016;387(10024):1187–97.CrossRef

14.

Minion J, Leung E, Talbot E, Dheda K, Pai M, Menzies D. Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and meta-analysis. Eur Respir J. 2011;38(6):1398–405. https://doi.org/10.1183/09031936.00025711.CrossRefPubMed

15.

Lawn SD, Kerkhoff AD, Burton R, Schutz C, Boulle A, Vogt M, Gupta-Wright A, Nicol MP, Meintjes G. Diagnostic accuracy, incremental yield and prognostic value of determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort. BMC Med. 2017;15(1):67. https://doi.org/10.1186/s12916-017-0822-8.CrossRefPubMedPubMedCentral

16.

Peter JG, Theron G, van Zyl-Smit R, Haripersad A, Mottay L, Kraus S, Binder A, Meldau R, Hardy A, Dheda K. Diagnostic accuracy of a urine lipoarabinomannan strip-test for TB detection in HIV-infected hospitalised patients. Eur Respir J. 2012;40(5):1211–20. https://doi.org/10.1183/09031936.00201711.CrossRefPubMedPubMedCentral

17.

Dheda K, Davids V, Lenders L, Roberts T, Meldau R, Ling D, Brunet L, van Zyl Smit R, Peter J, Green C, Badri M, Sechi L, Sharma S, Hoelscher M, Dawson R, Whitelaw A, Blackburn J, Pai M, Zumla A. Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS One. 2010;5(3):e9848. https://doi.org/10.1371/journal.pone.0009848.CrossRefPubMedPubMedCentral

18.

Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. BMJ. 2015;351:h5527.CrossRef

19.

Gupta-Wright A, Corbett EL, van Oosterhout JJ, Wilson D, Grint D, Alufandika-Moyo M, et al. Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial. Lancet (London, England). 2018;392(10144):292–301.CrossRef

20.

Naidoo K, De Vasconcellos K, Skinner D. Procalcitonin kinetics in the first 48 hours of ICU admission is associated with higher mortality in critically ill patients with community-acquired pneumonia in a setting of high HIV prevalence. South Afr J Anaesth Analg. 2018;24(5):128–34. https://doi.org/10.1080/22201181.2018.1514787.CrossRef

21.

Balkema CA, Irusen EM, Taljaard JJ, Koegelenberg CFN. Tuberculosis in the intensive care unit: a prospective observational study. Int J Tuberc Lung Dis. 2014;18(7):824–30. https://doi.org/10.5588/ijtld.13.0044.CrossRefPubMed

22.

Lee PL, Jerng JS, Chang YL, Chen CF, Hsueh PR, Yu CJ, et al. Patient mortality of active pulmonary tuberculosis requiring mechanical ventilation. 2003;22(1):141–7.

23.

Lawn SD, Gupta-Wright A. Detection of lipoarabinomannan (LAM) in urine is indicative of disseminated TB with renal involvement in patients living with HIV and advanced immunodeficiency: evidence and implications. Trans Royal Soc Trop Med Hyg. 2016;110(3):180–5. https://doi.org/10.1093/trstmh/trw008.CrossRef

24.

Paris L, Magni R, Zaidi F, Araujo R, Saini N, Harpole M, et al. Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity. Sci Transl Med. 2017;9(420).

25.

Kroidl I, Clowes P, Mwakyelu J, Maboko L, Kiangi A, Rachow A, Reither K, Jung J, Nsojo A, Saathoff E, Hoelscher M. Reasons for false-positive lipoarabinomannan ELISA results in a Tanzanian population. Scand J Infect Dis. 2014;46(2):144–8. https://doi.org/10.3109/00365548.2013.853133.CrossRefPubMed

26.

Drain PK, Gardiner J, Hannah H, Broger T, Dheda K, Fielding K, Walzl G, Kaforou M, Kranzer K, Joosten SA, Gilpin C, Weyer K, Denkinger CM, Schumacher SG. Guidance for studies evaluating the accuracy of biomarker-based nonsputum tests to diagnose tuberculosis. J Infect Dis. 2019;220(220 Suppl 3):S108–S15. https://doi.org/10.1093/infdis/jiz356.CrossRefPubMed

Title: The utility of point-of-care urinary lipoarabinomannan testing for the diagnosis of tuberculosis in critically ill patients: a prospective observational study
Authors: Kim de Vasconcellos
Praksha Ramjathan
Dhivendra Singh
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Tuberculosis
Tuberculosis
Care
Human Immunodeficiency Virus
Published in: BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-021-05979-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2021

Evaluation of different platforms for the detection of anti-SARS coronavirus-2 antibodies, Thailand

Predictors of willingness to get a COVID-19 vaccine in the U.S

The 12-month period prevalence and cardiac manifestations of HIV in patients with acute coronary syndrome at a tertiary hospital in Cape Town, South Africa: a retrospective cross-sectional study

Systematic review of invasive meningococcal disease epidemiology in the Eastern Mediterranean and North Africa region

Case report: aseptic meningitis secondary to varicella-zoster virus (VZV) without an exanthem post MMR vaccination

Clinical characteristics of children with airway malacia complicated by pneumonia

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials