Accuracy of a Novel Urine Test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan, for the Diagnosis of Pulmonary Tuberculosis in Children

Mark P Nicol; Samuel G Schumacher; Lesley Workman; Tobias Broger; Cynthia Baard; Margaretha Prins; Lindy Bateman; Elloise du Toit; Judi van Heerden; Rita Szekely; Heather J Zar; Claudia M Denkinger

doi:10.1093/cid/ciaa1052

Accuracy of a Novel Urine Test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan, for the Diagnosis of Pulmonary Tuberculosis in Children

Clin Infect Dis. 2021 May 4;72(9):e280-e288. doi: 10.1093/cid/ciaa1052.

Authors

Mark P Nicol^{1

2}, Samuel G Schumacher³, Lesley Workman⁴, Tobias Broger^{3

5}, Cynthia Baard⁴, Margaretha Prins⁴, Lindy Bateman⁴, Elloise du Toit², Judi van Heerden², Rita Szekely³, Heather J Zar⁴, Claudia M Denkinger^{3

5}

Affiliations

¹ Division of Infection and Immunity, School of Biomedical Sciences, University of Western Australia, Perth, Australia.
² Division of Medical Microbiology and Institute for Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
³ Foundation for Innovative New Diagnostics, Geneva, Switzerland.
⁴ Department of Paediatrics and Child Health and South African Medical Research Council Unit on Child and Adolescent Health, University of Cape Town and Red Cross War Memorial Children's Hospital, Cape Town, South Africa.
⁵ Division of Tropical Medicine, Centre of Infectious Diseases, University Hospital Heidelberg, Heidelberg, Germany.

Abstract

Background: An accurate point-of-care test for tuberculosis (TB) in children remains an elusive goal. Recent evaluation of a novel point-of-care urinary lipoarabinomannan test, Fujifilm SILVAMP Tuberculosis Lipoarabinomannan (FujiLAM), in adults living with human immunodeficiency virus (HIV) showed significantly superior sensitivity than the current Alere Determine Tuberculosis Lipoarabinomannan test (AlereLAM). We therefore compared the accuracy of FujiLAM and AlereLAM in children with suspected TB.

Methods: Children hospitalized with suspected TB in Cape Town, South Africa, were enrolled (consecutive admissions plus enrichment for a group of children living with HIV and with TB), their urine was collected and biobanked, and their sputum was tested with mycobacterial culture and Xpert MTB/RIF or Xpert MTB/RIF Ultra. Biobanked urine was subsequently batch tested with FujiLAM and AlereLAM. Children were categorized as having microbiologically confirmed TB, unconfirmed TB (clinically diagnosed), or unlikely TB.

Results: A total of 204 children were enrolled and had valid results from both index tests, as well as sputum microbiological testing. Compared to a microbiological reference standard, the sensitivity of FujiLAM and AlereLAM was similar (42% and 50%, respectively), but lower than that of Xpert MTB/RIF of sputum (74%). The sensitivity of FujiLAM was higher in children living with HIV (60%) and malnourished children (62%). The specificity of FujiLAM was substantially higher than that of AlereLAM (92% vs 66%, respectively). The specificity of both tests was higher in children 2 years or older (FujiLAM, 96%; AlereLAM, 72%).

Conclusions: The high specificity of FujiLAM suggests utility as a "rule-in" test for children with a high pretest probability of TB, including hospitalized children living with HIV or with malnutrition.

Keywords: LAM; children; diagnosis; lipoarabinomannan; tuberculosis.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Child
HIV Infections* / complications
Humans
Lipopolysaccharides
Mycobacterium tuberculosis*
Sensitivity and Specificity
South Africa
Sputum
Tuberculosis* / diagnosis
Tuberculosis, Pulmonary* / diagnosis

Substances

Lipopolysaccharides
lipoarabinomannan

Grants and funding

R01 HD058971/HD/NICHD NIH HHS/United States