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Open Access Highly Accessed Research article

Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria

Robin Wood123, Kimberly Racow1*, Linda-Gail Bekker12, Keren Middelkoop12, Monica Vogt1, Barry N Kreiswirth4 and Stephen D Lawn15

Author Affiliations

1 Desmond Tutu HIV Centre, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa

2 Department of Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa

3 Department of Science and Technology/National Research, Foundation Centre of Excellence in Epidemiological Modelling and Analysis, University of Stellenbosch, Stellenbosch, South Africa

4 Public Health Research Institute TB Center, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA

5 Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

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BMC Infectious Diseases 2012, 12:47  doi:10.1186/1471-2334-12-47

Published: 27 February 2012

Abstract

Background

Detection of lipoarabinomannan (LAM), a Mycobacterium tuberculosis (Mtb) cell wall antigen, is a potentially attractive diagnostic. However, the LAM-ELISA assay has demonstrated variable sensitivity in diagnosing TB in diverse clinical populations. We therefore explored pathogen and host factors potentially impacting LAM detection.

Methods

LAM-ELISA assay testing, sputum smear and culture status, HIV status, CD4 cell count, proteinuria and TB outcomes were prospectively determined in adults diagnosed with TB and commencing TB treatment at a South African township TB clinic. Sputum TB isolates were characterised by IS61110-based restriction fragment length polymorphism (RFLP) and urines were tested for mycobacteriuria by Xpert® MTB/RIF assay.

Results

32/199 (16.1%) of patients tested LAM-ELISA positive. Median optical density and proportion testing LAM positive remained unchanged during 2 weeks of treatment and then declined over 24 weeks. LAM was associated with positive sputum smear and culture status, HIV infection and low CD4 cell counts but not proteinuria, RFLP strain or TB treatment outcome. The sensitivity of LAM for TB in HIV-infected patients with CD4 counts of ≥ 200, 100-199, 50-99, and < 50 cells/μl, was 15.2%, 32%, 42.9%, and 69.2% respectively. Mycobacteriuria was found in 15/32 (46.9%) of LAM positive patients and in none of the LAM negative controls.

Conclusions

Urinary LAM was related to host immune factors, was unrelated to Mtb strain and declined steadily after an initial 2 weeks of TB treatment. The strong association of urine LAM with mycobacteriuria is a new finding, indicating frequent TB involvement of the renal tract in advanced HIV infection.