#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data


Autoři: Tobias Broger aff001;  Mark P. Nicol aff002;  Rita Székely aff001;  Stephanie Bjerrum aff005;  Bianca Sossen aff007;  Charlotte Schutz aff007;  Japheth A. Opintan aff009;  Isik S. Johansen aff005;  Satoshi Mitarai aff010;  Kinuyo Chikamatsu aff010;  Andrew D. Kerkhoff aff011;  Aurélien Macé aff001;  Stefano Ongarello aff001;  Graeme Meintjes aff007;  Claudia M. Denkinger aff001;  Samuel G. Schumacher aff001
Působiště autorů: FIND, Geneva, Switzerland aff001;  Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia aff002;  Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa aff003;  National Health Laboratory Service, Cape Town, South Africa aff004;  Mycobacterial Research Centre of Southern Denmark, Department of Infectious Diseases, Odense University Hospital, Odense, Denmark aff005;  Department of Clinical Research, Unit of Infectious Diseases, University of Southern Denmark, Odense, Denmark aff006;  Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa aff007;  Wellcome Center for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa aff008;  Department of Medical Microbiology, School of Biomedical and Allied Sciences, College of Health Sciences, University of Ghana, Accra, Ghana aff009;  Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association, Tokyo, Japan aff010;  Division of HIV, Infectious Diseases and Global Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, Department of Medicine, University of California, San Francisco, California, United States of America aff011;  Division of Tropical Medicine, Center for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany aff012
Vyšlo v časopise: Diagnostic accuracy of a novel tuberculosis point-of-care urine lipoarabinomannan assay for people living with HIV: A meta-analysis of individual in- and outpatient data. PLoS Med 17(5): e32767. doi:10.1371/journal.pmed.1003113
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pmed.1003113

Souhrn

Background

Tuberculosis (TB) is the most common cause of death in people living with HIV (PLHIV), yet TB often goes undiagnosed since many patients are not able to produce a sputum specimen, and traditional diagnostics are costly or unavailable. A novel, rapid lateral flow assay, Fujifilm SILVAMP TB LAM (SILVAMP-LAM), detects the presence of TB lipoarabinomannan (LAM) in urine, and is substantially more sensitive for diagnosing TB in PLHIV than an earlier LAM assay (Alere Determine TB LAM lateral flow assay [LF-LAM]). Here, we present an individual participant data meta-analysis of the diagnostic accuracy of SILVAMP-LAM in adult PLHIV, including both published and unpublished data.

Methods and findings

Adult PLHIV (≥18 years) were assessed in 5 prospective cohort studies in South Africa (3 cohorts), Vietnam, and Ghana, carried out during 2012 to 2017. Of the 1,595 PLHIV who met eligibility criteria, the majority (61%) were inpatients, median age was 37 years (IQR 30–43), 43% had a CD4 count ≤ 100 cells/μl, and 35% were receiving antiretroviral therapy. Most participants (94%) had a positive WHO symptom screen for TB on enrollment, and 45% were diagnosed with microbiologically confirmed TB, using mycobacterial culture or Xpert MTB/RIF testing of sputum, urine, or blood. Previously published data from inpatients were combined with unpublished data from outpatients. Biobanked urine samples were tested, using blinded double reading, with SILVAMP-LAM and LF-LAM. Applying a microbiological reference standard for assessment of sensitivity, the overall sensitivity for TB detection was 70.7% (95% CI 59.0%–80.8%) for SILVAMP-LAM compared to 34.9% (95% CI 19.5%–50.9%) for LF-LAM. Using a composite reference standard (which included patients with both microbiologically confirmed as well as clinically diagnosed TB), SILVAMP-LAM sensitivity was 65.8% (95% CI 55.9%–74.6%), and that of LF-LAM 31.4% (95% CI 19.1%–43.7%). In patients with CD4 count ≤ 100 cells/μl, SILVAMP-LAM sensitivity was 87.1% (95% CI 79.3%–93.6%), compared to 56.0% (95% CI 43.9%–64.9%) for LF-LAM. In patients with CD4 count 101–200 cells/μl, SILVAMP-LAM sensitivity was 62.7% (95% CI 52.4%–71.9%), compared to 25.3% (95% CI 15.8%–34.9%) for LF-LAM. In those with CD4 count > 200 cells/μl, SILVAMP-LAM sensitivity was 43.9% (95% CI 34.3%–53.9%), compared to 10.9% (95% CI 5.2%–18.4%) for LF-LAM. Using a microbiological reference standard, the specificity of SILVAMP-LAM was 90.9% (95% CI 87.2%–93.7%), and that of LF-LAM 95.3% (95% CI 92.2%–97.7%). Limitations of this study include the use of biobanked, rather than fresh urine samples, and testing by skilled laboratory technicians in research laboratories, rather than at the point of care.

Conclusions

In this study, we found that SILVAMP-LAM identified a substantially higher proportion of TB patients in PLHIV than LF-LAM. The sensitivity of SILVAMP-LAM was highest in patients with CD4 count ≤ 100 cells/μl. Further work is needed to demonstrate accuracy when implemented as a point-of-care test.

Klíčová slova:

Diagnostic medicine – HIV diagnosis and management – Inpatients – Outpatients – Sputum – Tuberculosis – Tuberculosis diagnosis and management – Urine


Zdroje

1. Hamada Y, Lujan J, Schenkel K, Ford N, Getahun H. Sensitivity and specificity of WHO’s recommended four-symptom screening rule for tuberculosis in people living with HIV: a systematic review and meta-analysis. Lancet HIV. 2018;5:e515–23. doi: 10.1016/S2352-3018(18)30137-1 30139576

2. Gupta-Wright A, Corbett EL, van Oosterhout JJ, Wilson D, Grint D, Alufandika-Moyo M, et al. Rapid urine-based screening for tuberculosis in HIV-positive patients admitted to hospital in Africa (STAMP): a pragmatic, multicentre, parallel-group, double-blind, randomised controlled trial. Lancet. 2018;392:292–301. doi: 10.1016/S0140-6736(18)31267-4 30032978

3. Peter JG, Zijenah LS, Chanda D, Clowes P, Lesosky M, Gina P, 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, randomised controlled trial. Lancet. 2016;387:1187–97. doi: 10.1016/S0140-6736(15)01092-2 26970721

4. Huerga H, Ferlazzo G, Bevilacqua P, Kirubi B, Ardizzoni E, Wanjala S, et al. Incremental yield of including Determine-TB LAM assay in diagnostic algorithms for hospitalized and ambulatory HIV-positive patients in Kenya. PLoS ONE. 2017;12:e0170976. doi: 10.1371/journal.pone.0170976 28125693

5. Boyles TH, Griesel R, Stewart A, Mendelson M, Maartens G. Incremental yield and cost of urine Determine TB-LAM and sputum induction in seriously ill adults with HIV. Int J Infect Dis. 2018;75:67–73. doi: 10.1016/j.ijid.2018.08.005 30125689

6. World Health Organization. High-priority target product profiles for new tuberculosis diagnostics: report of a consensus meeting. Geneva: World Health Organization; 2014 [cited 2020 Apr 9]. Available from: http://apps.who.int/iris/bitstream/10665/135617/1/WHO_HTM_TB_2014.18_eng.pdf.

7. 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. doi: 10.1186/1471-2334-12-103 22536883

8. Treatment Action Group. Tuberculosis diagnostics pipeline report 2019. New York: Treatment Action Group; 2019 [cited 2020 Apr 9]. Available from: https://www.treatmentactiongroup.org/resources/pipeline-report/2019-pipeline-report/.

9. Shah M, Hanrahan C, Wang ZY, Dendukuri N, Lawn SD, Denkinger CM, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in HIV-positive adults. Cochrane Database Syst Rev. 2016;(5):CD011420. doi: 10.1002/14651858.CD011420.pub2 27163343

10. Singhroy DN, MacLean E, Kohli M, Lessem E, Branigan D, England K, et al. Adoption and uptake of the lateral flow urine LAM test in countries with high tuberculosis and HIV/AIDS burden: current landscape and barriers. Gates Open Res. 2020;4:24. doi: 10.12688/gatesopenres.13112.2 32185366

11. Broger T, Sossen B, du Toit E, Kerkhoff AD, Schutz C, Ivanova Reipold E, et al. Novel lipoarabinomannan point-of-care tuberculosis test for people with HIV: a diagnostic accuracy study. Lancet Infect Dis. 2019;19:852–61. doi: 10.1016/S1473-3099(19)30001-5 31155318

12. Bjerrum S, Broger T, Székely R, Mitarai S, Opintan JA, Kenu E, et al. Diagnostic accuracy of a novel and rapid lipoarabinomannan test for diagnosing tuberculosis among people with human immunodeficiency virus. Open Forum Infect Dis. 2020;7:ofz530. doi: 10.1093/ofid/ofz530 31976353

13. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. doi: 10.1371/journal.pmed.1000097 19621072

14. Lawn SD, Kerkhoff AD, Burton R, Schutz C, Boulle A, Vogt M, et al. Diagnostic accuracy, incremental yield and prognostic value of Determine TB-LAM for routine diagnostic testing for tuberculosis in HIV-infected patients requiring acute hospital admission in South Africa: a prospective cohort. BMC Med. 2017;15:67. doi: 10.1186/s12916-017-0822-8 28320384

15. Schutz C, Barr D, Andrade BB, Shey M, Ward A, Janssen S, et al. Clinical, microbiologic, and immunologic determinants of mortality in hospitalized patients with HIV-associated tuberculosis: a prospective cohort study. PLoS Med. 2019;16:e1002840. doi: 10.1371/journal.pmed.1002840 31276515

16. Bjerrum S, Kenu E, Lartey M, Newman MJ, Addo KK, Andersen AB, et al. Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana—findings from the DETECT HIV-TB study. BMC Infect Dis. 2015;15:407. doi: 10.1186/s12879-015-1151-1 26427365

17. Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin Chem. 2015;61:1446–52. doi: 10.1373/clinchem.2015.246280 26510957

18. McInnes MDF, Moher D, Thombs BD, McGrath TA, Bossuyt PM, Clifford T, et al. Preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy studies. JAMA. 2018;319:388. doi: 10.1001/jama.2017.19163 29362800

19. FIND. Fujifilm SILVAMP TB LAM test procedure. YouTube. 2019 Apr 24 [cited 2020 Apr 9]. Available from: https://youtu.be/aK-QtzkLBug.

20. World Health Organization. Lateral flow urine lipoarabinomannan assay (LF-LAM) for the diagnosis of active tuberculosis in people living with HIV—policy update (2019). Geneva: World Health Organization; 2019 [cited 2020 Apr 9]. Available from: https://www.who.int/tb/publications/2019/diagnose_tb_hiv/en/.

21. Drain PK, Gardiner JL, Hannah H, Broger T, Dheda K, Fielding K, et al. Guidance for studies evaluating the accuracy of biomarker-based nonsputum tests to diagnose tuberculosis. J Infect Dis. 2019;220:S108–15. doi: 10.1093/infdis/jiz356 31593598

22. Guo J, Riebler A. meta4diag: Bayesian bivariate meta-analysis of diagnostic test studies for routine practice. J Stat Softw. 2018;83. doi: 10.18637/jss.v083.i01

23. Bjerrum S, Schiller I, Dendukuri N, Kohli M, Nathavitharana RR, Zwerling AA, et al. Lateral flow urine lipoarabinomannan assay for detecting active tuberculosis in people living with HIV. Cochrane Database Syst Rev. 2019;10:CD011420. doi: 10.1002/14651858.CD011420.pub3 31633805

24. Leeds IL, Magee MJ, Kurbatova EV, del Rio C, Blumberg HM, Leonard MK, et al. Site of extrapulmonary tuberculosis is associated with HIV infection. Clin Infect Dis. 2012;55:75–81. doi: 10.1093/cid/cis303 22423123

25. Sossen B, Broger T, Kerkhoff AD, Schutz C, Trollip A, Moreau E, et al. ‘SILVAMP TB LAM’ rapid urine tuberculosis test predicts mortality in patients hospitalized with human immunodeficiency virus in South Africa. Clin Infect Dis. 2020 Jan 9. doi: 10.1093/cid/ciaa024 31917832

26. Lawn SD, Kerkhoff AD, Nicol MP, Meintjes G. Underestimation of the true specificity of the urine lipoarabinomannan point-of-care diagnostic assay for HIV-associated tuberculosis. J Acquir Immune Defic Syndr. 2015;69:e144–6. doi: 10.1097/QAI.0000000000000672 25961395

27. Lawn SD, Kerkhoff AD, Burton R, Meintjes G. Underestimation of the incremental diagnostic yield of HIV-associated tuberculosis in studies of the Determine TB-LAM Ag urine assay. AIDS. 2014;28:1846–8. doi: 10.1097/QAD.0000000000000305 25006829

28. Sigal GB, Pinter A, Lowary TL, Kawasaki M, Li A, Mathew A, et al. A novel sensitive immunoassay targeting the 5-methylthio-d-xylofuranose–lipoarabinomannan epitope meets the WHO’s performance target for tuberculosis diagnosis. J Clin Microbiol. 2018;56. doi: 10.1128/JCM.01338-18 30257899

29. Kroidl I, Clowes P, Mwakyelu J, Maboko L, Kiangi A, Rachow A, et al. Reasons for false-positive lipoarabinomannan ELISA results in a Tanzanian population. Scand J Infect Dis. 2014;46:144–8. doi: 10.3109/00365548.2013.853133 24274710

30. Kawasaki M, Echiverri C, Raymond L, Cadena E, Reside E, Gler MT, et al. Lipoarabinomannan in sputum to detect bacterial load and treatment response in patients with pulmonary tuberculosis: analytic validation and evaluation in two cohorts. PLOS Med. 2019;16:e1002780. doi: 10.1371/journal.pmed.1002780 30978194

31. Broger T, Muyoyeta M, Kerkhoff AD, Denkinger CM, Moreau E. Tuberculosis test results using fresh versus biobanked urine samples with FujiLAM. Lancet Infect Dis. 2020;20:22–3. doi: 10.1016/S1473-3099(19)30684-X 31876492

32. 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;38:1398–405. doi: 10.1183/09031936.00025711 21700601


Článek vyšel v časopise

PLOS Medicine


2020 Číslo 5
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#