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

Broger, Tobias; Nicol, Mark P.; Székely, Rita; Bjerrum, Stephanie; Sossen, Bianca; Schutz, Charlotte; Opintan, Japheth A.; Johansen, Işik Somuncu; Mitarai, Satoshi; Chikamatsu, Kinuyo; Kerkhoff, Andrew D.; Macé, Aurélien; Ongarello, Stefano; Meintjes, Graeme; Denkinger, Claudia M.; Schumacher, Samuel G

doi:10.1371/journal.pmed.1003113

Cited by 65 publications

(71 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Specificity of FujiLAM in this study with HIV-negative patients was 98.9%, higher than AlereLAM’s specificity at 92.3% ( Figure 2 ). Earlier studies reported a lower specificity for FujiLAM ( 16 , 19 , 26 ) and the result from this study underlines the importance of a very comprehensive reference standard for a proper specificity assessment of urine biomarker tests ( 27 ).…”

Section: Discussionsupporting

confidence: 62%

“…FujiLAM was designed as a rule-in TB diagnostic test to allow rapid treatment initiation and reached a PPV of 95.2%. Together with its high sensitivity for TB diagnosis in people living with HIV ( 19 ) (sensitivity of 70.7% across CD4 strata), the FujiLAM might have considerable impact on the TB epidemic when scaled-up widely for use in near-patient settings. This is supported by a recent impact modeling analysis.…”

Section: Discussionmentioning

confidence: 99%

“…To improve sensitivity while maintaining high specificity, FujiLAM uses a pair of high-affinity monoclonal antibodies selected to detect LAM presenting the Mycobacterium tuberculosis –specific ( Mtb -specific) 5-Methylthio-D-xylofuranose epitope (MTX-LAM), and employs a silver-amplification step ( 16 – 18 ). A recent meta-analysis of 1595 HIV-positive inpatients and outpatients confirmed FujiLAM’s superiority, demonstrating a sensitivity of 71%, twice that of AlereLAM ( 19 ). Further, FujiLAM showed good sensitivity for the detection of extrapulmonary TB (EPTB) ranging from 47% to 94% across different forms of ETB ( 20 ) and could have rapidly diagnosed TB in up to 89% of HIV-positive inpatients who died within 12 weeks ( 21 ).…”

Section: Introductionmentioning

confidence: 95%

See 2 more Smart Citations

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Broger¹,

Nicol²,

Sigal³

et al. 2020

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

BACKGROUND Inadequate tuberculosis (TB) diagnostics are a major hurdle in the reduction of disease burden, and accurate point-of-care tests (POCTs) are urgently needed. We assessed the diagnostic accuracy of Fujifilm SILVAMP TB lipoarabinomannan (FujiLAM) POCT for TB diagnosis in HIV-negative outpatients and compared it with Alere Determine TB LAM Ag (AlereLAM) POCT and a laboratory-based ultrasensitive electrochemiluminescence LAM research assay (EclLAM). METHODS In this multicenter diagnostic test accuracy study, we recruited HIV-negative adults with symptoms suggestive of pulmonary TB presenting to outpatient health care centers in Peru and South Africa. Urine samples were tested using FujiLAM, AlereLAM, and EclLAM, and the diagnostic accuracy was assessed against a microbiological reference standard (MRS) and a composite reference standard. RESULTS Three hundred seventy-two HIV-negative participants were included and the prevalence of microbiologically confirmed TB was 30%. Compared with the MRS, the sensitivities of AlereLAM, FujiLAM, and EclLAM were 10.8% (95% confidence interval [CI] 6.3%–18.0%), 53.2% (95% CI 43.9%–62.1%), and 66.7% (95% CI 57.5%–74.7%), respectively. The specificities of AlereLAM, FujiLAM, and EclLAM were 92.3% (95% CI 88.5%–95.0%), 98.9% (95% CI 96.7%–99.6%), and 98.1% (95% CI 95.6%–99.2%), respectively. Positive likelihood ratios of AlereLAM, FujiLAM, and EclLAM were 1.4, 46.2, and 34.8, respectively, and positive predictive values were 37.5%, 95.2%, and 93.7%, respectively. CONCLUSION Compared with AlereLAM, FujiLAM detected 5 times more patients with TB in HIV-negative participants, had a high positive predictive value, and has the potential to improve rapid diagnosis of TB at the point-of-care. EclLAM demonstrated that additional sensitivity gains are possible, which highlights LAM’s potential as a biomarker. Additional research is required to assess FujiLAM’s performance in prospective cohorts, its cost-effectiveness, and its impact in real-world clinical settings. FUNDING Global Health Innovative Technology Fund, the UK Department for International Development, the Dutch Ministry of Foreign Affairs, the Bill and Melinda Gates Foundation, the Australian Department of Foreign Affairs and Trade, the German Federal Ministry of Education and Research through Kreditanstalt für Wiederaufbau, and the NIH and National Institute of Allergy and Infectious Diseases.

show abstract

Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

See 1 more Smart Citation

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Broger¹,

Nicol²,

Sigal³

et al. 2020

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additional studies in HIV-infected outpatients [31] and a recent meta-analysis of 1595 HIV-positive inpatients and outpatients [22] have confirmed FujiLAM's superiority over AlereLAM. The meta-analysis reported 70.7% (95% CI: 59.0-80.8%) sensitivity for FujiLAM, a sensitivity increase of 35.8% compared to AlereLAM [22]. FujiLAM also showed high performance for the detection of EPTB in HIV-infected patients [56].…”

Section: The Need For Next-generation Highly Sensitive and Specificmentioning

confidence: 88%

“…FujiLAM showed approximately 30% improved diagnostic sensitivity in HIV-positive inpatients compared to AlereLAM at 95.7% specificity [27]. Additional studies in HIV-infected outpatients [31] and a recent meta-analysis of 1595 HIV-positive inpatients and outpatients [22] have confirmed FujiLAM's superiority over AlereLAM. The meta-analysis reported 70.7% (95% CI: 59.0-80.8%) sensitivity for FujiLAM, a sensitivity increase of 35.8% compared to AlereLAM [22].…”

Section: The Need For Next-generation Highly Sensitive and Specificmentioning

confidence: 91%

Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update

Bulterys

Wagner

Redard-Jacot

et al. 2019

JCM

Self Cite

116

View full text Add to dashboard Cite

Most diagnostic tests for tuberculosis (TB) rely on sputum samples, which are difficult to obtain and have low sensitivity in immunocompromised patients, patients with disseminated TB, and children, delaying treatment initiation. The World Health Organization (WHO) calls for the development of a rapid, biomarker-based, non-sputum test capable of detecting all forms of TB at the point-of-care to enable immediate treatment initiation. Lipoarabinomannan (LAM) is the only WHO-endorsed TB biomarker that can be detected in urine, an easily collected sample. This status update discusses the characteristics of LAM as a biomarker, describes the performance of first-generation urine LAM tests and reasons for slow uptake, and presents considerations for developing the next generation of more sensitive and impactful tests. Next-generation urine LAM tests have the potential to reach adult and pediatric patients regardless of HIV status or site of infection and facilitate global TB control. Implementation and scale-up of existing LAM tests and development of next-generation assays should be prioritized.

show abstract

Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis

Zifodya

Kreniske

Schiller

et al. 2021

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

show abstract

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

Cited by 65 publications

References 29 publications

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients

Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update

Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis

Contact Info

Product

Resources

About