Introduction

Incarcerated populations worldwide suffer disproportionately high risk of both tuberculosis (TB) [1] and HIV infection,[2] a potent risk factor for TB. In response to the burden of tuberculosis and HIV in its correctional facilities, South Africa recently published national guidelines recommending symptom-based TB screening for all inmates bi-annually, on entry, exit or transfer, and self-presentation, with GeneXpert MTB/RIF as the initial diagnostic test for those requiring further evaluation.[3]

Tests for lipoarabinomannan (LAM), a cell wall lipopolysaccharide specific to mycobacteria that is detectable in urine, are a potentially attractive screening tool for correctional facilities, given the potential for rapid TB diagnosis, the low infection risk posed and ease of sample collection. Evaluations of a commercially available urine LAM ELISA (Clearview TB-ELISA; Alere, USA) have demonstrated sensitivity of 21–38% for culture-proven TB in HIV-positive individuals, [4, 5] which increases to 67% in those with CD4 cell counts <50 cells/μl.[5]

The aim of our study was, within the context of a TB prevalence survey in one of South Africa's largest correctional facilities,[6] to evaluate the diagnostic accuracy of the Clearview TB-ELISA for urine LAM to screen offenders for TB.

Methods

Results

Fig 1 summarises study inclusions, exclusions, case definitions, and urine LAM test results. Between September 2009 and October 2010, a total of 981 offenders were enrolled to the study. Amongst 871 evaluable participants, 871 (100%) were male, 812 (93%) were Black African, the median age was 32 (interquartile range [IQR] 27–38) years, 275 (32%) shared a cell with >50 offenders, and 110 (12.6%) reported at least one previous course of TB treatment. Median incarceration time in “currently incarcerated” offenders was 74 (IQR 43–103) months, and median detention in remand for new entrants was 14 (IQR 6–27) months. 222/871 (25.5%) offenders had a positive urine HIV test result.

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Fig 1. Participant flow chart.

LAM = lipoarabinomannan; TB = tuberculosis; S +ve = sputum smear-positive for acid-fast bacilli; S –ve = sputum smear-negative for acid-fast bacilli; C +ve = sputum culture-positive for M. tuberculosis; C –ve = sputum culture-negative for M. tuberculosis; CXR +ve = classical radiographic features of TB.

https://doi.org/10.1371/journal.pone.0127956.g001

33/871 (3.8%) participants fulfilled our case definition for definite and probable TB combined; five were smear-positive and 12 had any symptom compatible with TB. TB prevalence was greater amongst HIV-positive compared with HIV-negative offenders, 6.6% (14/212) vs. 3.0% (19/632), (P = 0.02).

5/871 (0.6%) participants had a positive LAM test result, of whom one was HIV-positive and sputum culture-positive for M. tuberculosis. Table 1 summarises the performance of the urine LAM test in our study population. Amongst HIV-positive offenders the sensitivity and specificity of the LAM assay were 7.1% (95% confidence interval [CI] 0.2%, 33.9%) and 98.5% (95% CI 95.6%, 99.7%) respectively. Amongst HIV-negative offenders the sensitivity and specificity of the LAM assay were 0% and 99.8% (95% CI 99.1%, >99.9%) respectively. The only TB case correctly identified by the urine LAM test was in an HIV-positive individual who was smear-negative, culture-positive, with compatible clinical but no radiological features of TB.

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Table 1. Performance of urine LAM test overall and stratified by HIV status compared with gold standard of bacteriologically-confirmed TB.

https://doi.org/10.1371/journal.pone.0127956.t001

Discussion

Our study has shown that the sensitivity of Clearview TB-ELISA is too low to be useful for the general screening of offenders in this correctional facility, of whom the majority are HIV-negative. Sensitivity was greater in those who were HIV-positive, in keeping with findings from a recent meta-analysis.[7] Indeed Clearview TB-ELISA is licensed as a screening test only in HIV-positive TB suspects. Evaluations amongst HIV-infected TB suspects have suggested that lateral flow urine test for LAM (Determine TB-LAM; Alere, USA) may be useful to rule-in TB in hospitalised patients with advanced immunosuppression with sensitivity and specificity of 66% for culture-proven TB [8]; and that the sensitivity of combination of smear microscopy with lateral flow LAM (72%) approaches that of Xpert MTB/RIF alone, [9] the latter study suggesting that these tests identified different groups of patients with TB. One limitation of our study is the lack of CD4 cell counts in those offenders confirmed to be HIV positive, and a possible explanation for the very low sensitivity (7%) amongst HIV-positive offenders, compared with other published data may be higher median CD4 cell count in this “healthier” population.

Despite the high prevalence of both HIV and TB among offenders, the low sensitivity of the urine LAM ELISA precludes recommendation of this test as a screening test for TB in this population. The results of our study reinforce the knowledge that the LAM assay, as reported previously in the literature, is not useful in populations with unknown HIV status and CD4 cell counts. [4, 7]

Acknowledgments

We would like to acknowledge the Department of Correctional Services of South Africa for their assistance and support during the study; the research nurses from the Aurum Institute (Mr. Griffiths Kubeka, Ms. Constance Ramatapa, Ms.Thelma Tlhabanelo and Mr.Tsohane Puso); Dr Cyrus Daneshvar (respiratory physician, Oxford University Hospitals NHS Trust, UK) for reading chest radiographs; Dr Natalie Beylis from the National Health Laboratory services of South Africa for microbiological support; and Dr Alan Karstaedt and Dr Natasha Davies from the Chris Hani Baragwanath Hospital South Africa for support in study design.