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Urine lipoarabinomannan assay for tuberculosis screening before antiretroviral therapy diagnostic yield and association with immune reconstitution disease

Lawn, Stephen Da,b; Edwards, David Ja; Kranzer, Katharinaa,b; Vogt, Monicaa; Bekker, Linda-Gaila; Wood, Robina

doi: 10.1097/QAD.0b013e32832e05c8
Clinical Science: Concise Communications

Objective: To assess the utility of urine lipoarabinomannan (LAM) detection as a diagnostic screening test for tuberculosis (TB) in HIV-infected patients with advanced immunodeficiency and high prevalence of sputum smear-negative pulmonary disease.

Design: Cross-sectional survey.

Methods: Unselected adults enrolling for antiretroviral therapy (ART) in a South African clinic were screened for TB with two sputum samples for fluorescence microscopy and mycobacterial liquid culture. LAM was measured in urine samples using a commercially available enzyme-linked immunosorbent assay.

Results: Sputum culture-positive TB was diagnosed in 58 patients (median CD4 cell count = 78 cells/μl) out of 235 patients screened (TB prevalence = 0.25). Cultures were identified as positive after a mean of 24 days (SD = 9 days). The sensitivity of sputum microscopy was just 0.14 (specificity = 1.00), whereas that of LAM in concentrated urine was 0.38 (P < 0.01; specificity = 1.00). In those with CD4 cell counts of less than 50, 50–100 and more than 150 cells/μl, the LAM assay sensitivities were 0.67, 0.41 and 0.13, respectively. Corresponding values for the combined use of the LAM assay and microscopy were 0.67, 0.53 and 0.21, respectively. Among TB patients, detectable LAM was very strongly associated with low CD4 cell counts and advanced clinical stage. All patients who developed TB immune reconstitution disease (n = 5) had detectable urinary LAM at baseline.

Conclusion: The LAM assay has substantially superior sensitivity to sputum microscopy as a routine diagnostic TB screening test among patients with CD4 cell counts less than 100 cells/μl. In one half of such patients, this assay could reduce the mean time to diagnosis by approximately 3 weeks. Furthermore, detectable urinary LAM may predict the development of TB immune reconstitution disease.

aThe Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

bClinical Research Unit, Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.

Received 6 March, 2009

Revised 1 May, 2009

Accepted 8 May, 2009

Correspondence to Stephen D. Lawn, Desmond Tutu HIV Centre, Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa. Tel: +27 21 650 6957; fax: +27 21 650 6963; e-mail: stevelawn@yahoo.co.uk

© 2009 Lippincott Williams & Wilkins, Inc.