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Clinical significance of lipoarabinomannan detection in urine using a low-cost point-of-care diagnostic assay for HIV-associated tuberculosis

Lawn, Stephen D.a,b; Kerkhoff, Andrew D.a,c; Vogt, Monicaa; Wood, Robina

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doi: 10.1097/QAD.0b013e3283553685
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Mortality rates are high among patients enrolling in antiretroviral therapy (ART) programmes in sub-Saharan Africa, with many deaths occurring in the period just prior to starting ART and during the first few months of treatment [1–3]. There is an urgent need for effective strategies to address this [4]. Tuberculosis (TB) represents an extremely important cause of morbidity and mortality in this period, and yet much of this disease remains undetected at baseline under routine programme conditions [5–7]. Intensified case finding (ICF) is therefore one of the critical interventions needed [8–10]. This has been hampered, however, by the very poor performance of the widely used first-line investigations – sputum smear microscopy and chest radiology [7,11]. Most disease is sputum smear-negative and chest radiology has very low sensitivity and specificity for TB diagnosis in those with advanced immunodeficiency [11,12].

The Xpert MTB/RIF rapid molecular assay is a major breakthrough in TB diagnostics [13–15] and has been endorsed by the WHO as a replacement for sputum smear microscopy in resource-limited settings [16]. However, the cost and infrastructure requirements are currently prohibitive in many poor countries [17] and simple, low-cost alternatives are needed. In South Africa, Xpert MTB/RIF is being implemented nationally, but only within centralized laboratories rather than at the district and sub-district levels, and this will inevitably result in ongoing delays in diagnosis. For example, although use of Xpert MTB/RIF for screening for TB in patients pre-ART in a South African township clinic increased case finding by 45% compared to sputum smear microscopy [18], delays associated with results reaching the clinic and with subsequent patient recall were substantial [19]. As a result, some patients died before starting TB treatment [20]. This treatment gap and the associated poor clinical outcomes would best be addressed by rapid point-of-care testing [20]. If TB diagnoses were made at patients’ first clinic visits, decisions could be made to start treatment immediately.

We have reported on the utility of the first low-cost, point-of-care diagnostic assay for HIV-associated TB [21]. This commercially available assay (Determine TB-LAM Ag; Alere Inc. Waltham, Massachusetts, USA) is a simple, lateral flow assay that detects the mycobacterial cell wall antigen lipoarabinomannan (LAM) in the urine of patients with HIV-associated TB regardless of anatomic location. The assay has useful diagnostic accuracy among patients with CD4 cell counts below 200 cells/μl and sensitivity increases at lower CD4 cell counts. We hypothesized that the patients with LAM detectable in urine (LAM-positive) would not only have more advanced immunodeficiency, but would also have higher mycobacterial load with disseminated disease and poorer prognosis. In this study, patients enrolling for ART were screened for TB using sputum smear microscopy, culture and Xpert and radiology, and were treated according to these results. We retrospectively assessed stored urine samples using Determine TB-LAM and compared the baseline characteristics and outcomes of patients with LAM-positive and LAM-negative TB. This analysis was restricted to those with a blood CD4 cell count below 200 cells/μl as these are the patients in which the assay has demonstrated utility [21].


The ART service in Gugulethu township, Cape Town, South Africa, has previously been described in detail, and the major burden of TB and high early mortality of patients attending this clinic have been characterized [3,5]. The current cohort of patients was enrolled between 12 March 2010 and 20 April 2011in the parent study assessing the diagnostic accuracy of Determine TB-LAM, and results have been reported [21]. Consecutive eligible HIV-infected patients were recruited from among patients newly referred to the clinic for ART. Study eligibility criteria included age above 18 years, being ART-naive and having no current TB diagnosis. All participants provided written informed consent and the study was approved by the research ethics committees of the University of Cape Town, South Africa, and the London School of Hygiene & Tropical Medicine, UK.

Patients were prospectively recruited at their first visit to the clinic, demographic details were recorded and they were clinically characterized. A standardized TB symptom-screening questionnaire (which included the WHO symptom screen for HIV-associated TB [22]) was completed and routine baseline investigations and screening tests for TB were done. Two sputum samples were requested from each patient; a spot specimen was first obtained followed by a second that was obtained by induction using nebulized 3% hypertonic saline. Urine samples were also collected and stored at −20oC within 3 h. Blood CD4 cell counts were measured by flow cytometry (Becton Dickinson, Franklin lakes, New Jersey, USA) and plasma viral load was measured using branched DNA technology (Bayer Diagnostics, Tarrytown, New York, USA). Chest radiographs were obtained and reported by an experienced reader certified in the use of the chest radiograph reading and recording system [12,23].

Laboratory procedures

Sputum specimens were processed using standardized protocols and quality assurance procedures by a centralized accredited laboratory. Samples were decontaminated with N-acetyl-L-cysteine and sodium hydroxide, and concentrated by centrifugation. Smears prepared from the sputum pellets were stained with auramine O fluorescent stain for fluorescence microscopy and equal volumes of the remaining pellet were tested by liquid culture and the Xpert MTB/RIF assay. All smears graded as scanty, 1+, 2+ and 3+ were defined as ‘smear-positive’. Culture was performed using Mycobacterial Growth Indicator Tubes (MGIT, Becton Dickinson, Sparks, Maryland, USA), which were incubated for up to 6 weeks. Cultures positive for acid-fast bacilli were identified as Mycobacterium tuberculosis complex using the MTBDRplus assay (Hain Lifesciences, Nehren, Germany). Xpert MTB/RIF assays were done according to the manufacturer's instructions. The results of all tests were read by technologists blinded to the outcomes of the other assays.

Frozen urine samples were defrosted and analysed for the presence of LAM using the commercially available Clearview TB-ELISA (Alere Inc.) with strict adherence to the manufacturer's instructions. Defrosted urine samples (2.0 ml) were also concentrated by centrifugation, resuspended in 0.75 ml of phosphate buffer and then tested using the Xpert MTB/RIF assay according to the manufacturer's instructions.

Urine samples were also tested in the laboratory using the Determine TB-LAM test (Lot #101102). Samples were first defrosted to ambient temperature and 60 μl was applied to the sample pad at the bottom of each test strip. Between 25 and 35 min later, the test was read under ambient laboratory lighting conditions by two investigators (S.D.L. and M.V.), comparing the test strips with a standardized reference card to facilitate reading. Each reader independently recorded the results, taking note of both the positive control bar and the sample test result. After comparison of the results, any discrepancies were discussed and the test strip reviewed within the 25–35-min time frame to reach consensus.

Patient outcomes

Patients were followed up within the routine ART service and patients diagnosed as having TB (including those diagnosed by Xpert MTB/RIF) were referred to TB clinics within the township for treatment. ART service patient records were reviewed to determine clinical outcomes. The proportions of patients who started TB treatment and ART and when these were started were recorded. Programme losses due to death, loss to follow-up or transfer-out were also ascertained.

Definitions and analysis

Patients were defined as having TB if M. tuberculosis was cultured from at least one sputum sample and analysis was restricted to those with a blood CD4 cell count below 200 cells/μl as these are the patients in which Determine TB-LAM has utility [21]. Patients were then defined as having LAM-positive or LAM-negative disease based on the finalized agreed result of urine testing using Determine TB-LAM. Characteristics and 30 and 90-day outcomes of patients with LAM-positive and LAM-negative TB were compared using the Wilcoxon rank-sum test, t-test, chi-square and Fisher's exact tests as appropriate. Logistic regression analysis was used to identify factors independently associated with LAM-positive test results. All statistical tests were two-sided at alpha 0.05.


Tuberculosis diagnoses

Of 604 consecutive patients who were eligible and invited to participate in the parent study, 602 agreed to enrol [21]. Sputum and urine samples were obtained from 535 (88.9%) patients (Fig. 1) and complete results were available from 514 (96.1%) of these. Blood CD4 cell counts were below 200 cells/μL in 325 of these patients who were therefore eligible for inclusion in this analysis. M. tuberculosis was cultured from one or both sputum samples from 59 patients, giving a prevalence of culture-positive pulmonary TB of 18.2% [95% confidence interval (CI) 14.1–22.8]. Eighteen (30.5%) cases were sputum smear-positive and 41 (69.5%) were smear-negative.

Fig. 1
Fig. 1:
Flow diagram showing patients included in the analysis.

Tuberculosis cases were young adults who were predominantly female (Table 1). One-fifth had a history of previous TB treatment. The median [interquartile range (IQR)] CD4 cell count was 100 (35–145) cells/μl and the median plasma viral load was very high. Almost half of the patients had WHO stage 3 or 4 (AIDS) disease at enrolment before the current TB diagnosis was made. A positive WHO TB symptom screen was recorded in 81.4% of TB patients, but only 28.8% reported a cough lasting at least 2 weeks.

Table 1
Table 1:
Characteristics of patients (n = 59) with tuberculosis (TB) stratified according to urine lipoarabinomannan (LAM) result.

Characteristics of patients with lipoarabinomannan-positive tuberculosis

Results of the independent blinded reading of the Determine TB-LAM test strips by the two readers were compared and agreement was observed in 58 of the 59 (98.3%) urine samples. With consensus reached for the one discrepancy, finalized results showed that 23 (39.0%) culture-confirmed TB cases had urine that tested LAM-positive and 36 (61.0%) had urine that tested LAM-negative.

Compared to LAM-negative cases, LAM-positive cases had characteristics that indicated greater morbidity and more advanced immunodeficiency (Table 1). They were three times more likely to report cough lasting at least 2 weeks and they had lower BMIs. Haematological parameters revealed that LAM-positive patients had substantially lower haemoglobin concentrations and higher neutrophil counts. Their median CD4 cell count was almost three times lower than that of LAM-negative cases and viral loads were substantially higher.

In multivariate analysis, strong associations were observed between testing LAM-positive and low haemoglobin, low BMI, and low blood CD4 cell count (Table 2). A weaker association was also seen with higher blood neutrophil counts.

Table 2
Table 2:
Univariate and multivariate analysis using linear logistic regression showing the association between patient characteristics and risk of a positive urine lipoarabinomannan.

Comparison with other investigations for tuberculosis

The diagnostic sensitivities of smear microscopy, Xpert MTB/RIF (one sputum test) and Xpert MTB/RIF (two sputum tests) overall were 30.5, 62.7 and 76.3%, respectively (Table 3). Smear and Xpert results were both available with a median turnaround time of 4 days. The median time to receiving positive culture results was 18 days for all culture-positive TB cases and 21 days for the sub-set with sputum smear-negative disease.

Table 3
Table 3:
Results of microbiological and radiological investigations for tuberculosis (TB) among all TB patients and those with Determine TB-LAM-positive or Determine TB-LAM-negative TB.

We next compared the results of other microbiological investigations of LAM-positive and LAM-negative cases and also their pulmonary radiographic features (Table 3). Collectively, the microbiological tests indicated that LAM-positive cases had higher mycobacterial burden. This was shown by such cases being more likely to have positive sputum smears and positive Xpert results when testing either sputum or urine. In addition, the median time to sputum culture positivity was substantially shorter for LAM-positive cases reflecting greater bacillary numbers in sputum samples.

Pulmonary radiographs were available for 57 TB cases and were abnormal in 79% of these and normal in 21% (Table 3). Consistent with advanced HIV-associated immunodeficiency, mediastinal and/or hilar lymphadenopathy were observed in almost one-third of cases and none had pulmonary cavitation. There were no differences in pulmonary radiographic features when comparing LAM-positive and LAM-negative cases.

Patient outcomes

We determined outcomes of all patients up to 90 days from the time of programme enrolment and TB screening (Table 4). Overall, 79.7% were alive and retained in the programme after 30 days and 72.9% were retained after 90 days. Only three-quarters of patients started TB treatment within 90 days, a median of 14.5 days (IQR 8–30 days) after screening. Five (8.5%) patients died and a further 7 (11.9%) were lost to follow-up.

Table 4
Table 4:
Early antiretroviral treatment (ART) programme outcomes of all patients with culture-positive TB stratified according to whether lipoarabinomannan (LAM) was detectable in urine.

We next compared the outcomes of patients with LAM-positive and LAM-negative TB (Table 4). Smaller proportions of LAM-positive cases were alive and retained in the programme after 30 and 90 days (65.2 and 52.2%, respectively) compared those with LAM-negative disease (88.9 and 86.1%, respectively). Of the five deaths that occurred in the first 30-day period (between 10 and 21 days after enrolment and screening), all were patients whose urine retrospectively tested LAM-positive.

Although 21 (91.3%) of the LAM-positive TB cases had positive sputum Xpert MTB/RIF results that triggered the start TB treatment, only 65.2% of these patients actually received treatment within 30 days of screening (Table 4). Moreover, positive sputum Xpert MTB/RIF results were also obtained for all the patients who died (n = 5) and yet only one of these had started TB treatment prior to death on the basis of a chest radiograph showing miliary TB.

In contrast to LAM-positive TB cases, LAM-negative cases had a better prognosis despite a median time to starting TB treatment which was three times longer (8 versus 24 days) (Table 4). The prolonged treatment delay in the LAM-negative group reflected the smaller proportions of patients who tested smear-positive or Xpert-positive and the fact that TB treatment was therefore started in many of these patients on the basis of culture results.


There is great need for rapid and simple point-of-care diagnosis of TB among patients accessing ART services in resource-limited settings to address the huge burden of morbidity and mortality [4,7]. This is especially needed for those with the lowest CD4 cell counts and highest mortality risk in whom TB treatment should be started without delay. In this study, it was striking that despite the availability of high-sensitivity rapid molecular testing for TB in a centralized laboratory service, delays or failure to start TB treatment were common. Mortality was high (8.5%) and four of the five patients died without starting TB treatment. When retrospectively testing stored urine samples for LAM using Determine TB-LAM, we found that the assay diagnosed TB in a sub-group of patients who had more advanced immunodeficiency, higher mycobacterial load and worse prognosis, including the five patients who died. Had this assay been used in the clinic during initial screening visit, approximately 40% of the sickest patients might have been able to start TB treatment immediately. The chances of survival of those who died without TB treatment may thereby have been improved.

In the parts of sub-Saharan Africa worst affected by the HIV and TB epidemics, the prevalence of undiagnosed TB among patients enrolling in ART clinics is so high and the clinical presentation so nonspecific as to warrant routine microbiological screening of all patients [6,7,24]. When available, culture-based diagnosis has far superior diagnostic accuracy compared to smear microscopy and chest radiology, but it requires considerable technical infrastructure and is prohibitively expensive for most countries. Moreover, it is unacceptably slow with a median turnaround time of over 3 weeks for smear-negative patients in this study. The Xpert MTB/RIF rapid molecular assay is a potential ‘game-changer’ in many respects [13], especially when implemented at the district and sub-district level [15]. However, in the few resource-limited countries that can afford to implement this technology at a programme level, it is very likely to be located in centralized laboratories. This will inevitably be associated with delays in connecting the results with the patients, undermining its diagnostic utility and patient outcomes [20]. Delays in diagnosis and treatment included the time for the sample to reach the laboratory, be processed, the results issued and reach the clinic and for the patients to return to the clinic following recall. During this time period, some patients die or are lost to follow-up [19,20].

Assays that detect LAM in urine samples are emerging to fill a specific diagnostic niche, permitting rapid diagnosis of TB in patients with HIV infection and advanced immunodeficiency (CD4 cell counts <200 cells/μl). These assays were first developed commercially in the format of a 96-well plate ELISA [25]. Subsequent field evaluations found that despite poor sensitivity among non-HIV-infected patients [26,27], LAM ELISAs have moderately high sensitivity and high specificity when screening patients enrolling for ART [24] and in HIV-infected medical in-patients [28]. The development of a simple, low-cost ($3.50 per test), lateral-flow (urine strip test) version of the assay is a major step forward as it permits TB diagnosis in these patient groups within 30 min in the clinic consultation room or at the bedside [19]. Determine TB-LAM test strips were found to have very similar diagnostic accuracy as the laboratory-based ELISA format [21]. When used in combination with smear microscopy, the sensitivity (72%) was the same as that of Xpert MTB/RIF in patients with CD4 cell counts below 50 cells/μl [21].

The study clearly demonstrates that despite the overall sub-optimal sensitivity of Determine TB-LAM, the assay nevertheless rapidly diagnoses TB in a sub-set of patients with poor prognostic features. These patients had much more advanced immunodeficiency, were more likely to be anaemic and have a low BMI consistent with more advanced and disseminated TB disease. These characteristics are all strong independent predictors of high mortality risk in ART programmes [1]. Collectively, other microbiological investigations also provided evidence of high mycobacterial burden in patients with LAM-positive urine samples. All patients who died during follow-up tested LAM-positive and thus Determine TB-LAM may have the potential to reduce mortality risk by allowing immediate initiation of TB treatment in such patients.

A range of different diagnostic options are now emerging for TB screening prior to starting ART, and appropriate selection cannot simply be based on diagnostic accuracy, but also on feasibility, speed of diagnosis, cost and likely impact. There are various attractive combinations that might be used in settings with differing resources. The major advantage of Determine TB-LAM is the ability to use it at the point of care, permitting immediate initiation of TB treatment, especially in those with the worst prognostic features. However, limited sensitivity means that it cannot be used as a stand-alone test [29]. When used in combination with smear microscopy, there is important incremental sensitivity [21]. Together these assays would diagnose the patients with the worst prognosis (LAM-positive) as well as those who are the most infectious (sputum smear-positive) who constitute the greatest infection hazard to others in the clinic and the community.

Chest radiography permits rapid patient evaluation, but the radiological features of HIV-associated TB in those with CD4 cell counts below 200 cells/μl are often very nonspecific [11,12]. The differential diagnosis of abnormal radiographs is often difficult and time-consuming to resolve. However, the positive predictive value of Determine TB-LAM for TB is high among those with radiographic abnormalities [21] and thus combined testing would increase diagnostic specificity in those with abnormal radiographs.

When resources permit, an algorithm in which patients were screened with Determine TB-LAM at point of care and with laboratory-based Xpert MTB/RIF would diagnose all smear-positive patients, a substantial proportion of smear-negative patients and would also permit immediate initiation of TB treatment in the sickest (LAM-positive) patients [29]. Although this combination of assays would still miss a significant minority of patients with disease that can be detected by sputum culture (LAM-negative/Xpert-negative/culture-positive), such patients have good prognosis [20] and low TB transmission risk, allowing time for repeat screening.

This is the first study to report on the characteristics and early outcomes of patients with LAM-positive and LAM-negative TB. Strengths of this study include the careful characterization of TB patients and comparison of a range of different diagnostic tests. Unselected patients were consecutively enrolled to the parent study [21], but analysis was restricted to patients with CD4 cell counts below 200 cells/μl as this is the sub-group in which the assay has utility. ART programme losses were carefully ascertained by peer counsellors as previously described [30] and yet deaths among those lost to follow-up cannot be definitively excluded. Urine samples were analysed retrospectively and the diagnostic accuracy and ease of use at the point of care is as yet unknown. Also it remains to be determined whether use of the Determine TB-LAM assay at the point of care has any impact on clinical outcomes.

In conclusion the Determine TB-LAM assay is able to provide a rapid TB diagnosis in a sub-group of patients enrolling in ART services who have poor prognostic characteristics and high risk of death. Implementation of this assay at the point of care and used in combination with laboratory-based diagnostics may help to reduce mortality from HIV-associated TB in ART services in resource-limited settings.


We thank sister Pearl Pahlana and the staff of the Hannan Crusaid ART clinic.

S.D.L. was funded by the Wellcome Trust, London, UK. R.W. was funded in part by the National Institutes of Health (NIH) through grants RO1 A1058736–01A1, 5UO1A1069519–02 and USAID grant 3UO1A1069924-O2S. We are grateful to the Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland for providing access to the Xpert MTB/RIF assay cartridges with preferential pricing. Alere provided the LAM assays free of charge. None of these sources played any role in the design, conduct, analysis, interpretation or decision to publish these data.

Conflicts of interest

The authors have no conflicts of interest to declare.


1. Lawn SD, Harries AD, Anglaret X, Myer L, Wood R. Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa. AIDS 2008; 22:1897–1908.
2. Braitstein P, Brinkhof MW, Dabis F, Schechter M, Boulle A, Miotti P, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006; 367:817–824.
3. Lawn SD, Myer L, Orrell C, Bekker LG, Wood R. Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design. AIDS 2005; 19:2141–2148.
4. Lawn SD, Harries AD, Wood R. Strategies to reduce early morbidity and mortality in adults receiving antiretroviral therapy in resource-limited settings. Curr Opin HIV AIDS 2010; 5:18–26.
5. Lawn SD, Myer L, Bekker LG, Wood R. Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control. AIDS 2006; 20:1605–1612.
6. Bassett IV, Wang B, Chetty S, Giddy J, Losina E, Mazibuko M, et al. Intensive tuberculosis screening for HIV-infected patients starting antiretroviral therapy in Durban, South Africa. Clin Infect Dis 2010; 51:823–829.
7. Lawn SD, Wood R. Tuberculosis in antiretroviral treatment services in resource-limited settings: addressing the challenges of screening and diagnosis. J Infect Dis 2011; 204 (Suppl 4):S1159–S1167.
8. World Health Organization. WHO three I's meeting. Report of a joint WHO HIV/AIDS and TB Department Meeting, 2008. WHO, Geneva. Accessed on 12th Jan 2012 at: http://
9. Kranzer K, Houben RM, Glynn JR, Bekker LG, Wood R, Lawn SD. Yield of HIV-associated tuberculosis during intensified case finding in resource-limited settings: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10:93–102.
10. Lawn SD, Kranzer K, Edwards DJ, McNally M, Bekker LG, Wood R. Tuberculosis during the first year of antiretroviral therapy in a South African cohort using an intensive pretreatment screening strategy. AIDS 2010; 24:1323–1328.
11. Reid MJ, Shah NS. Approaches to tuberculosis screening and diagnosis in people with HIV in resource-limited settings. Lancet Infect Dis 2009; 9:173–184.
12. Dawson R, Masuka P, Edwards DJ, Bateman ED, Bekker LG, Wood R, et al. Chest radiograph reading and recording system: evaluation for tuberculosis screening in patients with advanced HIV. Int J Tuberc Lung Dis 2010; 14:52–58.
13. Lawn SD, Nicol MP. Xpert(R) MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance. Future Microbiol 2011; 6:1067–1082.
14. Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 2010; 363:1005–1015.
15. Boehme CC, Nicol MP, Nabeta P, Michael JS, Gotuzzo E, Tahirli R, et al. Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study. Lancet 2011; 377:1495–1505.
16. WHO. Tuberculosis diagnostics automated DNA test. WHO endorsement and recommendations. World Health Organization, Geneva, 2010. Accessed on 12 Jan 2012 at: http://
17. Trebucq A, Enarson DA, Chiang CY, Van Deun A, Harries AD, Boillot F, et al. Xpert(R) MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how?. Int J Tuberc Lung Dis 2011; 15:1567–1572.
18. Lawn SD, Brooks SV, Kranzer K, Nicol MP, Whitelaw A, Vogt M, et al. Screening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay: a prospective study. PLoS Med 2011; 8:e1001067.
19. Lawn SD, Kerkhoff AD, Vogt M, Ghebrekristos Y, Whitelaw A, Wood R. Characteristics and early outcomes of patients with Xpert MTB/RIF-negative pulmonary tuberculosis diagnosed during screening before antiretroviral therapy. Clin Infect Dis 2012; 54:1071–1079.
20. Lawn SD, Kerkhoff AD, Wood R. Location of Xpert(R) MTB/RIF in centralised laboratories in South Africa undermines potential impact. Int J Tuberc Lung Dis 2012; 16:701.
21. 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; 12:201–209.
22. Getahun H, Kittikraisak W, Heilig CM, Corbett EL, Ayles H, Cain KP, et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med 2011; 8:e1000391.
23. Den Boon S, Bateman ED, Enarson DA, Borgdorff MW, Verver S, Lombard CJ, et al. Development and evaluation of a new chest radiograph reading and recording system for epidemiological surveys of tuberculosis and lung disease. Int J Tuberc Lung Dis 2005; 9:1088–1096.
24. Lawn SD, Edwards DJ, Kranzer K, Vogt M, Bekker LG, Wood R. Urine lipoarabinomannan assay for tuberculosis screening before antiretroviral therapy diagnostic yield and association with immune reconstitution disease. AIDS 2009; 23:1875–1880.
25. Boehme C, Molokova E, Minja F, Geis S, Loscher T, Maboko L, et al. Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg 2005; 99:893–900.
26. Achkar JM, Lawn SD, Moosa MY, 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–S1141.
27. 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 [Epub ahead of print]
28. Shah M, Variava E, Holmes CB, Coppin A, Golub JE, McCallum J, et al. Diagnostic accuracy of a urine lipoarabinomannan test for tuberculosis in hospitalized patients in a High HIV prevalence setting. J Acquir Immune Defic Syndr 2009; 52:145–151.29.
29. 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; 12:103.
30. Lawn SD, Myer L, Harling G, Orrell C, Bekker LG, Wood R. Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation. Clin Infect Dis 2006; 43:770–776.

Africa; antiretroviral; diagnosis; HIV; LAM; lipoarabinomannan; screening; tuberculosis

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