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): e1003113. doi:10.1371/journal.pmed.1003113
Kategorie: Research Article
doi: 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

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PLOS Medicine


2020 Číslo 5

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