Skip to main content
Top
Published in: BMC Pulmonary Medicine 1/2016

Open Access 01-12-2016 | Research article

Rapid urine lipoarabinomannan assay as a clinic-based screening test for active tuberculosis at HIV diagnosis

Authors: Paul K. Drain, Elena Losina, Sharon M. Coleman, Janet Giddy, Douglas Ross, Jeffrey N. Katz, Ingrid V. Bassett

Published in: BMC Pulmonary Medicine | Issue 1/2016

Login to get access

Abstract

Background

World Health Organization (WHO) recommends tuberculosis (TB) screening at HIV diagnosis. We evaluated the inclusion of rapid urine lipoarabinomannan (LAM) testing in TB screening algorithms.

Methods

We enrolled ART-naïve adults who screened HIV-infected in KwaZulu-Natal, assessed TB-related symptoms (cough, fever, night sweats, weight loss), and obtained sputum specimens for mycobacterial culture. Trained nurses performed clinic-based urine LAM testing using a rapid assay. We used diagnostic accuracy, negative predictive value (NPV), and negative likelihood ratio, stratified by CD4 count, to evaluate screening for culture-positive TB.

Results

Among 675 HIV-infected adults with median CD4 of 213/mm3 (interquartile range 85-360/mm3), 123 (18%) had culture-confirmed pulmonary TB. The WHO-recommended algorithm of any TB-related symptom had a sensitivity of 77% [95% confidence interval (CI) 69-84%] and NPV of 89% (95% CI 84-92%) for identifying active pulmonary TB. Including the LAM assay improved sensitivity (83%; 95% CI 75-89%) and NPV (91%; 95% CI 86-94%), while decreasing the negative likelihood ratio (0.45 versus 0.57). Among participants with CD4 < 100/mm3, including urine LAM testing improved the negative predictive value of symptom based screening from 83% to 87%. All screening algorithms with urine LAM performed better among participants with CD4 < 100/mm3, compared to those with CD4 ≥ 100/mm3.

Conclusion

Clinic-based urine LAM screening increased the sensitivity of symptom-based screening by 6% among ART-naïve HIV-infected adults in a TB-endemic setting, thereby providing marginal benefit.
Literature
1.
go back to reference World Health Organization. Global tuberculosis report 2015. Geneva: World Health Organization; 2015. World Health Organization. Global tuberculosis report 2015. Geneva: World Health Organization; 2015.
2.
go back to reference World Health Organization. WHO policy on collaborative TB/HIV activities. Geneva: World Health Organization; 2012. World Health Organization. WHO policy on collaborative TB/HIV activities. Geneva: World Health Organization; 2012.
3.
go back to reference World Health Organization. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Geneva: World Health Organization; 2006. World Health Organization. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Geneva: World Health Organization; 2006.
4.
go back to reference Stop TB Partnership, World Health Organization Global TB Programme. Reach the 3 million: Find. Treat. Cure TB. Geneva: World Health Organization; 2014. Stop TB Partnership, World Health Organization Global TB Programme. Reach the 3 million: Find. Treat. Cure TB. Geneva: World Health Organization; 2014.
5.
go back to reference World Health Organization. Systematic screening for active tuberculosis: principles and recommendations. Geneva: World Health Organization; 2013. World Health Organization. Systematic screening for active tuberculosis: principles and recommendations. Geneva: World Health Organization; 2013.
6.
go back to reference World Health Organization. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva: World Health Organization; 2011. World Health Organization. Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings. Geneva: World Health Organization; 2011.
7.
go back to reference Getahun H, Kittikraisak W, Heilig CM, 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.CrossRefPubMedPubMedCentral Getahun H, Kittikraisak W, Heilig CM, 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.CrossRefPubMedPubMedCentral
8.
go back to reference Rangaka M, Wilkinson RJ, Glynn JR, et al. Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening for intensified case finding in a South African HIV clinic. Clin Infect Dis. 2012;55:1698–706.CrossRefPubMedPubMedCentral Rangaka M, Wilkinson RJ, Glynn JR, et al. Effect of antiretroviral therapy on the diagnostic accuracy of symptom screening for intensified case finding in a South African HIV clinic. Clin Infect Dis. 2012;55:1698–706.CrossRefPubMedPubMedCentral
9.
go back to reference World Health Organization. Rapid Implementation of the Xpert MTB/RIF diagnostic test: Technical and Operational ‘How-to’; Practical considerations. Geneva: World Health Organization; 2011. World Health Organization. Rapid Implementation of the Xpert MTB/RIF diagnostic test: Technical and Operational ‘How-to’; Practical considerations. Geneva: World Health Organization; 2011.
10.
go back to reference Lester R, Hamilton R, Charalambous S, et al. Barriers to implementation of isoniazid preventive therapy in HIV clinics: a qualitative study. AIDS. 2010;24 Suppl 5:S45–8.CrossRefPubMed Lester R, Hamilton R, Charalambous S, et al. Barriers to implementation of isoniazid preventive therapy in HIV clinics: a qualitative study. AIDS. 2010;24 Suppl 5:S45–8.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
12.
go back to reference Peter JG, Zijenah LS, Chanda D, 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, randomized controlled trial. Lancet. 2016;Published online 9 March 2016. Peter JG, Zijenah LS, Chanda D, 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, randomized controlled trial. Lancet. 2016;Published online 9 March 2016.
13.
go back to reference Drain PK, Losina E, Coleman SM, et al. Diagnostic accuracy of a point-of-care urine test for tuberculosis screening among newly-diagnosed HIV-infected adults: a prospective, clinic-based study. BMC Infect Dis. 2014;14:110.CrossRefPubMedPubMedCentral Drain PK, Losina E, Coleman SM, et al. Diagnostic accuracy of a point-of-care urine test for tuberculosis screening among newly-diagnosed HIV-infected adults: a prospective, clinic-based study. BMC Infect Dis. 2014;14:110.CrossRefPubMedPubMedCentral
14.
go back to reference Drain PK, Losina E, Coleman SM, et al. Value of Urine Lipoarabinomannan Grade and Second Test for Optimizing Clinic-Based Screening for HIV-Associated Pulmonary Tuberculosis. J Acquir Immune Defic Syndr. 2015;68:274–80.CrossRefPubMedPubMedCentral Drain PK, Losina E, Coleman SM, et al. Value of Urine Lipoarabinomannan Grade and Second Test for Optimizing Clinic-Based Screening for HIV-Associated Pulmonary Tuberculosis. J Acquir Immune Defic Syndr. 2015;68:274–80.CrossRefPubMedPubMedCentral
15.
go back to reference 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;12:201–9.CrossRefPubMedPubMedCentral 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;12:201–9.CrossRefPubMedPubMedCentral
16.
go back to reference Shah M, Hanrahan C, Wang Z, Dendukuri N, Lawn SD, Denkinger CM, Steingart KR. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database of Systematic Reviews. 2016; (Issue 5). Art. No.: CD011420. DOI: 10.1002/14651858.CD011420.pub2 Shah M, Hanrahan C, Wang Z, Dendukuri N, Lawn SD, Denkinger CM, Steingart KR. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database of Systematic Reviews. 2016; (Issue 5). Art. No.: CD011420. DOI: 10.​1002/​14651858.​CD011420.​pub2
17.
go back to reference World Health Organization. The use of lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis and screening of active tuberculosis in people living with HIV; Policy guidance. Geneva: World Health Organization; 2015. World Health Organization. The use of lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis and screening of active tuberculosis in people living with HIV; Policy guidance. Geneva: World Health Organization; 2015.
18.
go back to reference Bassett IV, Giddy J, Chaisson CE, et al. A randomized trial to optimize HIV/TB care in South Africa: design of the Sizanani trial. BMC Infect Dis. 2013;13:390.CrossRefPubMedPubMedCentral Bassett IV, Giddy J, Chaisson CE, et al. A randomized trial to optimize HIV/TB care in South Africa: design of the Sizanani trial. BMC Infect Dis. 2013;13:390.CrossRefPubMedPubMedCentral
19.
go back to reference Department of Health, Republic of South Africa. The South African Antiretroviral Treatment Guidelines 2013. Pretoria: Department of Health; 2013. Department of Health, Republic of South Africa. The South African Antiretroviral Treatment Guidelines 2013. Pretoria: Department of Health; 2013.
20.
go back to reference Liu TT, Wilson D, Dawood H, Cameron DW, Alvarez GG. Inaccuracy of death certificate diagnosis of tuberculosis and potential underdiagnosis of TB in a region of high HIV prevalence. Clin Dev Immunol. 2012;2012:937013.PubMedPubMedCentral Liu TT, Wilson D, Dawood H, Cameron DW, Alvarez GG. Inaccuracy of death certificate diagnosis of tuberculosis and potential underdiagnosis of TB in a region of high HIV prevalence. Clin Dev Immunol. 2012;2012:937013.PubMedPubMedCentral
21.
go back to reference Denkinger CM. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva: World Health Organization; 2014. Denkinger CM. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva: World Health Organization; 2014.
22.
go back to reference Denkinger CM, Kik SV, Cirillo DM, et al. Defining the needs for next generation assays to Tuberculosis. J Infect Dis. 2015;211(Suppl 2):S29–38. doi:10.1093/infdis/jiu821. Denkinger CM, Kik SV, Cirillo DM, et al. Defining the needs for next generation assays to Tuberculosis. J Infect Dis. 2015;211(Suppl 2):S29–38. doi:10.​1093/​infdis/​jiu821.
23.
go back to reference Cain KP, McCarthy KD, Heilig CM, et al. An algorithm for tuberculosis screening and diagnosis in people with HIV. N Engl J Med. 2010;362:707–16.CrossRefPubMed Cain KP, McCarthy KD, Heilig CM, et al. An algorithm for tuberculosis screening and diagnosis in people with HIV. N Engl J Med. 2010;362:707–16.CrossRefPubMed
24.
go back to reference Chheng P, Tamhane A, Natpratan C, et al. Pulmonary tuberculosis among patients visiting a voluntary confidential counseling and testing center, Cambodia. Int J Tuberc Lung Dis. 2008;12:54–62.PubMed Chheng P, Tamhane A, Natpratan C, et al. Pulmonary tuberculosis among patients visiting a voluntary confidential counseling and testing center, Cambodia. Int J Tuberc Lung Dis. 2008;12:54–62.PubMed
25.
go back to reference 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;23:1875–80.CrossRefPubMed 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;23:1875–80.CrossRefPubMed
26.
go back to reference Van’t Hoog A, Cobelens FG, Vassall A, et al. Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis. PLoS One. 2013;8:e82786.CrossRef Van’t Hoog A, Cobelens FG, Vassall A, et al. Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis. PLoS One. 2013;8:e82786.CrossRef
27.
Metadata
Title
Rapid urine lipoarabinomannan assay as a clinic-based screening test for active tuberculosis at HIV diagnosis
Authors
Paul K. Drain
Elena Losina
Sharon M. Coleman
Janet Giddy
Douglas Ross
Jeffrey N. Katz
Ingrid V. Bassett
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Pulmonary Medicine / Issue 1/2016
Electronic ISSN: 1471-2466
DOI
https://doi.org/10.1186/s12890-016-0316-z

Other articles of this Issue 1/2016

BMC Pulmonary Medicine 1/2016 Go to the issue