Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies

BMC Infectious Diseases

Mark P Nicol⁴  Catharina C Boehme³  Susan Dorman⁷  Jonathan G Peter⁶  Andrew D Kerkhoff¹  Keertan Dheda²  Stephen D Lawn⁵ 

[1] George Washington University School of Medicine and Health Sciences, Washington, DC, USA;Lung Infection and Immunity Unit, Division of Pulmonology & UCT Lung Institute, Department of Medicine, University of Cape Town, Cape Town, South Africa;Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland;National Health Laboratory Service, Groote Schuur Hospital, Cape Town, South Africa;The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa;TB vaccine group, Jenner Institute, University of Oxford, Oxford, UK;Johns Hopkins University School of Medicine, Baltimore, MD, USA

关键词: Point-of-care;    Specificity;    Sensitivity;    Diagnostic accuracy;    Diagnosis;    Tuberculosis;    Lipoarabinomannan;    Determine TB-LAM Ag;   

Others  :  1145890
DOI  :  10.1186/1471-2334-13-407

 received in 2013-07-11, accepted in 2013-08-30,  发布年份 2013

【 摘 要 】

Detection of the Mycobacterium tuberculosis cell wall antigen lipoarabinomannan (LAM) in urine permits diagnoses of tuberculosis (TB) to be made in HIV-infected patients with advanced immunodeficiency. This can be achieved at the point-of-care within just 30 minutes using the Determine TB-LAM, which is a commercially available, lateral-flow urine ‘strip test’ assay. The assay has been shown to have useful diagnostic accuracy in patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards in sub-Saharan Africa. Such patients have high mortality risk and have most to gain from rapid diagnosis of TB and immediate initiation of treatment. However, few studies using this assay have yet been reported and many questions remain concerning the correct use of the assay, interpretation of results, the role of the assay as an add-on test within existing diagnostic algorithms and the types of further studies needed. In this paper we address a series of questions with the aim of informing the design, conduct and interpretation of future studies. Specifically, we clarify which clinical populations are most likely to derive benefit from use of this assay and how patients enrolled in such studies might best be characterised. We describe the importance of employing a rigorous microbiological diagnostic reference standard in studies of diagnostic accuracy and discuss issues surrounding the specificity of the assay in different geographical areas and potential cross-reactivity with non-tuberculous mycobacteria and other organisms. We highlight the importance of careful procedures for urine collection and storage and the critical issue of how to read and interpret the test strips. Finally, we consider how the assay could be used in combination with other assays and outline the types of studies that are required to build the evidence base concerning its use.

【 授权许可】

   
2013 Lawn et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Lawn SD, Zumla AI: Tuberculosis. Lancet 2011, 378:57-72.
• [2]Lucas SB, Hounnou A, Peacock C, Beaumel A, Djomand G, N’Gbichi JM, Yeboue K, Honde M, Diomande M, Giordano C: The mortality and pathology of HIV infection in a west African City. AIDS 1993, 7:1569-1579.
• [3]Rana FS, Hawken MP, Mwachari C, Bhatt SM, Abdullah F, Ng’ang’a LW, Power C, Githui WA, Porter JD, Lucas SB: Autopsy study of HIV-1-positive and HIV-1-negative adult medical patients in Nairobi, Kenya. J Acquir Immune Defic Syndr 2000, 24:23-29.
• [4]Ansari NA, Kombe AH, Kenyon TA, Hone NM, Tappero JW, Nyirenda ST, Binkin NJ, Lucas SB: Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997–1998. Int J Tuberc Lung Dis 2002, 6:55-63.
• [5]Cohen T, Murray M, Wallengren K, Alvarez GG, Samuel EY, Wilson D: The prevalence and drug sensitivity of tuberculosis among patients dying in hospital in KwaZulu-Natal, South Africa: a postmortem study. PLoS Med 2010, 7:e1000296.
• [6]Boehme CC, Nabeta P, Hillemann D, Nicol MP, Shenai S, Krapp F, Allen J, Tahirli R, Blakemore R, Rustomjee R, et al.: Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 2010, 363:1005-1015.
• [7]Lawn SD, Mwaba P, Bates M, Piatek A, Alexander H, Marais BJ, Cuevas LE, McHugh TD, Zijenah L, Kapata N, et al.: Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test. Lancet Infect Dis 2013, 13:349-361.
• [8]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. BioMed Central Full Text
• [9]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.
• [10]Cohen G, Drain P, Noubary F, Cloete C, Nixon K, Parker G, Bassett I: Diagnostic delays associated with xpert MTB/RIF assay in a centralized laboratory for pulmonary TB among HIV-positive adults in South Africa. Atlanta, GA, USA: Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections; 2013. Abstract #846
• [11]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.
• [12]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.
• [13]Holtz TH, Kabera G, Mthiyane T, Zingoni T, Nadesan S, Ross D, Allen J, Chideya S, Sunpath H, Rustomjee R: Use of a WHO-recommended algorithm to reduce mortality in seriously ill patients with HIV infection and smear-negative pulmonary tuberculosis in South Africa: an observational cohort study. Lancet Infect Dis 2011, 11:533-540.
• [14]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, 38:1398-1405.
• [15]Peter JG, Theron G, Zyl-Smit R, Haripersad A, Mottay L, Kraus S, Binder A, Meldau R, Hardy A, Dheda K: Diagnostic accuracy of a urine lipoarabinomannan strip-test for TB detection in HIV-infected hospitalised patients. Eur Respir J 2012, 40:1211-1220.
• [16]Dorman S, Manabe Y, Nicol M, Nakiyingi L, Moodley M, Zemanay W, Holshouser M, Perkins M, Alland D, Ellner J: Accuracy of determine TB-LAM lateral flow test for diagnosis of TB in HIV + adults: interim results from a multicenter study. Seattle, Washington: Program and Abstracts of the 19th Conference on Retroviruses and Opportunistic Infections; 2012. Abstract # 149aLB
• [17]Van Rie A, Jong E, Mkhwanazi M, Sanne I: Diagnosing TB in those hardest to diagnose: urine lipoarabinomannan for suspects of disseminated and extrapulmonary TB. Atlanta, USA: Abstract of the 20th Conference on Retroviruses and Opportunistic Infections (CROI); 2013. Abstract #841
• [18]Drain P, Losina E, Coleman S, Giddy J, Ross D, Parker G, Katz J, Walensky R, Freedberg K, Bassett I: A prospective, clinic-based study of a urine lipoarabinomannan test for pulmonary or extrapulmonary TB among HIV-positiveAdults: South Africa. Atlanta, USA: Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections (CROI); 2013. Abstract #842
• [19]Shah M, Ssengooba W, Armstrong D, Nakiyingi L, Holshouser M, Ellner J, Joloba M, Manabe Y, Dorman S: Comparative performance of rapid urinary lipoarabinomannan assays and xpert MTB/RIF in HIV-positiveTB suspects: Uganda. Atlanta, USA: Program and abstracts of the 20th Conference on Retroviruses and Opportunistic Infections (CROI); 2013. Abstract #146
• [20]Lawn SD, Kerkhoff AD, Vogt M, Wood R: Clinical significance of lipoarabinomannan detection in urine using a low-cost point-of-care diagnostic assay for HIV-associated tuberculosis. AIDS 2012, 26:1635-1643.
• [21]Peter JG, Theron G, Dheda K: Can point-of-care urine LAM strip testing for tuberculosis add value to clinical decision making in hospitalised HIV-infected persons? PLoS ONE 2013, 8:e54875.
• [22]Kerkhoff AD, Wood R, Vogt M, Lawn SD: Diagnostic accuracy of novel sputum and urine assays for HIV-associated TB: correlation with C-reactive protein concentration and mortality risk. Atlanta, GA, USA: 20th Conference on Retroviruses and Opportunistic Infections; 2013. Abstract #843
• [23]Lawn SD, Kerkhoff AD, Vogt M, Wood R: Diagnostic and prognostic value of serum C-reactive protein for screening for HIV-associated tuberculosis. Int J Tuberc Lung Dis 2013, 17:636-643.
• [24]Gabay C, Kushner I: Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999, 340:448-454.
• [25]Lawn SD, Kerkhoff AD, Pahlana P, Vogt M, Wood R: Diagnostic yield of tuberculosis using sputum induction in HIV-positive patients before antiretroviral therapy. Int J Tuberc Lung Dis 2012, 16:1354-1357.
• [26]Peter JG, Theron G, Singh N, Singh A, Dheda K: Sputum induction to aid the diagnosis of smear-negative or sputum-scarce TB in adults from a HIV-endemic setting. Eur Respir J 2013. e-pub ahead of print
• [27]Peter JG, Theron G, Pooran A, Thomas J, Pascoe M, Dheda K: Evaluation of two sputum sample acquisition methods for the diagnosis of suspected tuberculosis in smear-negative or sputum-scarce persons in primary care practice: a randomised controlled trial. Lancet Resp Med 2011. in press
• [28]Shah M, Martinson NA, Chaisson RE, Martin DJ, Variava E, Dorman SE: Quantitative analysis of a urine-based assay for detection of lipoarabinomannan in patients with tuberculosis. J Clin Microbiol 2010, 48:2972-2974.
• [29]Van Rie A, Page-Shipp L, Mellet K, Scott L, Mkhwnazi M, Jong E, Omar T, Beylis N, Stevens W, Sanne I, et al.: Diagnostic accuracy and effectiveness of the Xpert MTB/RIF assay for the diagnosis of HIV-associated lymph node tuberculosis. Eur J Clin Microbiol Infect Dis 2013. e-pub ahead of print
• [30]Ligthelm LJ, Nicol MP, Hoek KG, Jacobson R, van Helden PD, Marais BJ, Warren RM, Wright CA: Xpert MTB/RIF for rapid diagnosis of tuberculous lymphadenitis from fine-needle-aspiration biopsy specimens. J Clin Microbiol 2011, 49:3967-3970.
• [31]Lawn SD, Kerkhoff AD, Vogt M, Wood R: High diagnostic yield of tuberculosis from screening urine samples from HIV-infected patients with advanced immunodeficiency using the Xpert MTB/RIF assay. J Acquir Immune Defic Syndr 2012, 60:289-294.
• [32]Peter JG, Theron G, Muchinga TE, Govender U, Dheda K: The diagnostic accuracy of urine-based Xpert MTB/RIF in HIV-infected hospitalized patients who are smear-negative or sputum scarce. PLoS ONE 2012, 7:e39966.
• [33]Wood R, Racow K, Bekker LG, Middelkoop K, Vogt M, Kreiswirth BN, Lawn SD: Lipoarabinomannan in urine during tuberculosis treatment: association with host and pathogen factors and mycobacteriuria. BMC Infect Dis 2012, 12:47. BioMed Central Full Text
• [34]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.
• [35]Shah M, Variava E, Holmes CB, Coppin A, Golub JE, McCallum J, Wong M, Luke B, Martin DJ, Chaisson RE, 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.
• [36]Dheda K, Davids V, Lenders L, Roberts T, Meldau R, Ling D, Brunet L, van Zyl SR, Peter J, Green C, et al.: Clinical utility of a commercial LAM-ELISA assay for TB diagnosis in HIV-infected patients using urine and sputum samples. PLoS ONE 2010, 5:e9848.
• [37]Gounder CR, Kufa T, Wada NI, Mngomezulu V, Charalambous S, Hanifa Y, Fielding K, Grant A, Dorman S, Chaisson RE, et al.: Diagnostic accuracy of a urine lipoarabinomannan enzyme-linked immunosorbent assay for screening ambulatory HIV-infected persons for TB. J Acquir Immune Defic Syndr 2011, 58:219-223.
• [38]Mutetwa R, Boehme C, Dimairo M, Bandason T, Munyati SS, Mangwanya D, Mungofa S, Butterworth AE, Mason PR, Corbett EL: Diagnostic accuracy of commercial urinary lipoarabinomannan detection in African tuberculosis suspects and patients. Int J Tuberc Lung Dis 2009, 13:1253-1259.
• [39]Daley P, Michael JS, Hmar P, Latha A, Chordia P, Mathai D, John KR, Pai M: Blinded evaluation of commercial urinary lipoarabinomannan for active tuberculosis: a pilot study. Int J Tuberc Lung Dis 2009, 13:989-995.
• [40]Reither K, Saathoff E, Jung J, Minja LT, Kroidl I, Saad E, Huggett JF, Ntinginya EN, Maganga L, Maboko L, et al.: Low sensitivity of a urine LAM-ELISA in the diagnosis of pulmonary tuberculosis. BMC Infect Dis 2009, 9:141. BioMed Central Full Text
• [41]Mukundan H, Kumar S, Price DN, Ray SM, Lee YJ, Min S, Eum S, Kubicek-Sutherland J, Resnick JM, Grace WK, et al.: Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. Tuberculosis (Edinb) 2012, 92:407-416.
• [42]Posthuma-Trumpie GA, Korf J, van Amerongen A: Lateral flow (immuno) assay: its strengths, weaknesses, opportunities and threats. A literature survey. Anal Bioanal Chem 2009, 393:569-582.
• [43]Lawn SD, Kerkhoff AD, Burton R, Scutz C, Van Wyk G, Vogt M, Pahlana P, Nicol M, Meintjes G: Rapid screening for TB in HIV-infected medical in-patient admissions in South Africa: massive incremental yield using a novel urine-based diagnostic strategy (interim analysis). Paris: Abstracts of the 44th Union World Conference on Lung Health. International Union Against Tuberculosis and Lung Disease; 2013. Late breaker abstract #