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Novel High Sensitivity Tuberculosis Point-of-Care Test for People Living with HIV

86 Pages Posted: 28 Sep 2018

See all articles by Tobias Broger

Tobias Broger

Foundation for Innovative New Diagnostics (FIND)

Bianca Sossen

University of Cape Town (UCT)

Elloise du Toit

University of Cape Town (UCT)

Andrew D. Kerkhoff

University of California, San Francisco (UCSF)

Charlotte Schutz

University of Cape Town (UCT)

Elena Ivanova Reipold

Foundation for Innovative New Diagnostics (FIND)

Amy Ward

University of Cape Town (UCT)

David A. Barr

University of Liverpool

Aurélien Macé

Foundation for Innovative New Diagnostics (FIND)

Rosie Burton

Rutgers, The State University of New Jersey

Stefano Ongarello

Foundation for Innovative New Diagnostics (FIND)

Abraham Pinter

Rutgers, The State University of New Jersey

Catharina Boehme

Foundation for Innovative New Diagnostics (FIND)

Mark P. Nicol

University of Cape Town (UCT)

Graeme Meintjes

University of Cape Town (UCT); University of Cape Town (UCT) - Institute for Infectious Disease & Molecular Medicine; University of Cape Town (UCT) - Department of Medicine

Claudia Denkinger

Foundation for Innovative New Diagnostics (FIND)

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Abstract

Background: Most tuberculosis-related deaths in people living with HIV (PLHIV) could be prevented with earlier diagnosis and treatment. The only commercially available tuberculosis point-of-care test (Alere DetermineTM TB LAM Ag (AlereLAM)) has suboptimal sensitivity which restricts its use in clinical practice. The novel Fujifilm SILVAMP TB LAM (FujiLAM) test was designed to achieve superior diagnostic accuracy.  

Methods: We performed a blinded assessment of FujiLAM on biobanked urine samples from three independent prospective cohort studies of hospitalized PLHIV at two South African district hospitals. Diagnostic accuracy was determined against both microbiological (MRS) and composite reference standards (CRS, including clinical diagnoses), in comparison with AlereLAM.  

Findings: A total of 968 newly admitted PLHIV were included. The prevalence of microbiologically-confirmed TB was 62% and the median CD4 count 86 cells/µl. In a meta-analysis, the estimated sensitivity of the FujiLAM was superior at 70·4% (95%CI: 53·0-83·1) over that of AlereLAM at 42·3% (31·7-51·8), against the MRS, with a difference of 28.1% (21.5-34.4). Specificities were 90·8% (86·0-94·4) and 95·0% (87·7-98·8) for the FujiLAM and AlereLAM against the MRS, respectively, with a non-significant difference of -4.2% (-12.7-4.4). Against the CRS, specificities of both assays were higher (FujiLAM 95·7% and AlereLAM 98·2%) but sensitivities were lower (FujiLAM 64·9% and AlereLAM 38·2%). In the subgroup of patients with CD4 ≤100 cells/µl, the sensitivity of FujiLAM was 84·2% (71·4-91·4) versus 57·3% (42·2-69·6) for AlereLAM.  

Interpretation: In comparison to AlereLAM, FujiLAM offers superior diagnostic sensitivity, while maintaining specificity, and has the potential to transform rapid point-of-care tuberculosis diagnosis for hospitalized PLHIV. FujiLAM's suitability for settings of intended use needs to be assessed in a prospective evaluation.  

Funding: GHIT Fund, UK DFID, Dutch MoFA, BMGF, Australian DFAT, German BMBF through KfW, Wellcome Trust, DST/ NRF of South Africa, and South African MRC.

Declaration of Interest: TB, EI, AM, SO, CCB, and CMD are 384 employed by FIND. FIND is a not for-profit foundation that supports the evaluation of publicly prioritized tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics for tuberculosis and other diseases. These agreements strictly define FIND’s independence and neutrality vis-a-vis the companies whose products get evaluated and describe roles and responsibilities. AP and TB report patents in the field of lipoarabinomannan detection. All other authors declare no competing interests.

Ethical Approval: All study-related activities were approved by the Human Research Ethics Committee (HREC) of the University of Cape Town (UCT). Written informed consent was obtained from patients, as per study protocols. Study participation did not affect standard of care. Reporting followed STARD guidelines.12 167 Retrospective urine LAM testing was supervised by the sponsor, FIND, and was performed at UCT in April 2018.

Suggested Citation

Broger, Tobias and Sossen, Bianca and du Toit, Elloise and Kerkhoff, Andrew D. and Schutz, Charlotte and Reipold, Elena Ivanova and Ward, Amy and Barr, David A. and Macé, Aurélien and Burton, Rosie and Ongarello, Stefano and Pinter, Abraham and Boehme, Catharina and Nicol, Mark P. and Meintjes, Graeme and Denkinger, Claudia, Novel High Sensitivity Tuberculosis Point-of-Care Test for People Living with HIV (September 21, 2018). Available at SSRN: https://ssrn.com/abstract=3254479

Tobias Broger

Foundation for Innovative New Diagnostics (FIND)

Geneva
Switzerland

Bianca Sossen

University of Cape Town (UCT)

Private Bag X3
Rondebosch, Western Cape 7701
South Africa

Elloise Du Toit

University of Cape Town (UCT)

Private Bag X3
Rondebosch, Western Cape 7701
South Africa

Andrew D. Kerkhoff

University of California, San Francisco (UCSF)

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Charlotte Schutz

University of Cape Town (UCT)

Private Bag X3
Rondebosch, Western Cape 7701
South Africa

Elena Ivanova Reipold

Foundation for Innovative New Diagnostics (FIND)

Geneva
Switzerland

Amy Ward

University of Cape Town (UCT)

Private Bag X3
Rondebosch, Western Cape 7701
South Africa

David A. Barr

University of Liverpool

Chatham Street
Liverpool, L69 7ZA
United Kingdom

Aurélien Macé

Foundation for Innovative New Diagnostics (FIND)

Geneva
Switzerland

Rosie Burton

Rutgers, The State University of New Jersey

311 North 5th Street
New Brunswick, NJ 08854
United States

Stefano Ongarello

Foundation for Innovative New Diagnostics (FIND)

Geneva
Switzerland

Abraham Pinter

Rutgers, The State University of New Jersey

311 North 5th Street
New Brunswick, NJ 08854
United States

Catharina Boehme

Foundation for Innovative New Diagnostics (FIND)

Geneva
Switzerland

Mark P. Nicol

University of Cape Town (UCT)

Private Bag X3
Rondebosch, Western Cape 7701
South Africa

Graeme Meintjes

University of Cape Town (UCT)

Private Bag X3
Rondebosch, Western Cape 7701
South Africa

University of Cape Town (UCT) - Institute for Infectious Disease & Molecular Medicine

Rondebosch, Western Cape
South Africa

University of Cape Town (UCT) - Department of Medicine

Private Bag X3
Rondebosch, 7701
South Africa

Claudia Denkinger (Contact Author)

Foundation for Innovative New Diagnostics (FIND) ( email )

Geneva
Switzerland

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